JP4548728B2 - Polyhydroxyalkanoate having vinyl group, ester group, carboxyl group and sulfonic acid group and method for producing the same - Google Patents

Description

  The present invention relates to a novel polyhydroxyalkanoate and a method for producing the same.

  Biodegradable polymer materials are widely applied to medical materials, drug delivery systems, and environmentally compatible materials. In recent years, in addition to these, new functions have been required, and various studies have been conducted. In particular, for polyhydroxyalkanoates typified by polylactic acid, it has been studied to introduce functional groups that can be chemically modified into the molecule, and there have been reports on compounds having a carboxyl group or a vinyl group introduced therein. For example, polymalic acid is known as a polyhydroxyalkanoate having a carboxyl group in the side chain. This polymalic acid polymer has chemical formula (14), depending on how the polymer is formed.

Α type represented by the chemical formula (15),

The β type represented by is known. Of these, β-type polymalic acid and copolymers thereof are described in US Pat. No. 4,265,247 (Patent Document 1), chemical formula (16),

(R _16: a benzyl group)
A polymer obtained by ring-opening polymerization of a benzyl ester of β-malolactone represented by the formula: In addition, an α-type polymalic acid-glycolic acid copolymer and a copolymer containing other hydroxyalkanoic acids such as glycolic acid are described in JP-A-2-3415 (Patent Document 2) as chemical formula ( 17)

(R ₁₇ is a lower alkyl group such as methyl group, ethyl group, n-propyl group, isopropyl group, t-butyl group, and benzyl group)
A copolymer obtained by copolymerizing a cyclic diester with glycolide and lactide, and a lactone that is an intramolecular ring-closing ester of ω-hydroxycarboxylic acid is disclosed.

  Moreover, as polyhydroxyalkanoate which has a carboxyl group in a side chain, ring opening polymerization of 7-oxo-4-oxepanecarboxylic acid ester is carried out to Macromolecules 2000,33 (13), 4619-4627 (nonpatent literature 1). It was disclosed that a polymer having an ester group in the side chain was produced and further hydrocracked to produce a polymer having a carboxylic acid in the side chain. Biomacromolecules 2000, 1, 275 (Non-patent Document 2) includes a poly (ε-caprolactone) main chain by reacting poly (ε-caprolactone) with lithium diisopropylamide and further reacting with benzyl chloroformate. A polymer in which a benzyloxycarbonyl group is introduced into a methylene group at the α-position of a carbonyl group therein is disclosed. In Macromolecular Bioscience 2004, 4, 232 (Non-patent Document 3), by reacting polylactic acid with lithium diisopropylamide and further reacting with benzyl bromoacetate, α of the carbonyl group in the main chain of polylactic acid is obtained. Polymers in which a (benzyloxycarbonyl) methyl group is introduced into the methylene group at the position are disclosed.

  As a polyhydroxyalkanoate having a vinyl group in the side chain, a polymer obtained by ring-opening polymerization of α-allyl (δ-valerolactone) is disclosed in Polymer Materials Science & Engineering 2002, 87,254 (Non-patent Document 4). Similarly, as a polyhydroxyalkanoate having a vinyl group in the side chain, Polymer Preprints 2002, 43 (2), 727 (Non-patent Document 5) describes 3,6-diallyl-1, which is a 6-membered ring diester monomer. A polymer obtained by ring-opening polymerization of 4-dioxane-2,5-dione is disclosed.

There has been a report on a polymer having a new function by further introducing a structure that imparts functionality to the polyhydroxyalkanoate into which a functional group that can be chemically modified is introduced as described above. International Journal of Biological Macromolecules 25 (1999) 265 (Non-patent Document 6) obtained a copolymer of α-type malic acid and glycolic acid by ring-opening polymerization of a cyclic dimer of α-malic acid and glycolic acid. The resulting polymer is deprotected to obtain a polyester having a carboxyl group in the side chain. When the tripeptide was chemically modified to the carboxyl group of this side chain and the resulting polymer was evaluated for cell adhesiveness, good results were obtained.
U.S. Pat. No. 4,265,247 Japanese Patent Laid-Open No. 2-3415 Macromolecules 2000,33 (13), 4619-4627 Biomacromolecules 2000, 1, 275 Macromolecular Bioscience 2004, 4, 232 Polymeric Materials Science & Engineering 2002, 87,254 Polymer Preprints 2002, 43 (2), 727 International Journal of Biological Macromolecules 25 (1999) 265

  As described above, it is not possible to add new functionality by introducing a unit having a carboxyl group that is a reactive functional group or a unit having a vinyl group into the molecule and chemically modifying the reactive functional group. There are few reported cases. Therefore, the present invention provides a novel polyhydroxyalkanoate having a reactive functional group in the molecule and a method for producing the same, and a novel polyhydroxyalkanoate having a new function by chemically modifying the polyhydroxyalkanoate having the reactive functional group. A polyhydroxyalkanoate and a method for producing the same are provided.

  Therefore, the present inventors have developed a novel polyhydroxyalkanoate having a reactive functional group in the molecule and a novel polyhydroxyalkanoate having a new function by chemically modifying the polyhydroxyalkanoate having the reactive functional group. As a result of intensive research aimed at the development of alkanoates, the inventors have reached the following inventions.

The polyhydroxyalkanoate according to the present invention includes the following.
(1) A polyhydroxyalkanoate containing at least one unit represented by the chemical formula (1) in the molecule.

(Wherein, .R ₁ R is representative of a -A ₁ -SO ₂ R ₁ is OH, halogen atom, ONa, OK, or is OR _1a .R _1a and A ₁ each independently represents a substituted or unsubstituted aliphatic Represents a group having an aromatic hydrocarbon structure, a substituted or unsubstituted aromatic ring structure, or a substituted or unsubstituted heterocyclic structure, wherein l is an integer selected from 1 to 4, and n is 1 M is an integer selected from 0 to 8. When a plurality of units are present, R, R ₁ , R _1a , A ₁ , l, m and n are each (2) A polyhydroxyalkanoate containing one or more units represented by the chemical formula (5).

(In the formula, R ₅ is hydrogen, a group forming a salt, or R _5a . R _5a has a linear or branched alkyl group having 1 to 12 carbon atoms, an aralkyl group, or a saccharide. L is an integer selected from 1 to 4, n is an integer selected from 1 to 4, m is an integer selected from 0 to 8, and 1 is 1 In the case of 3, 4 and 4, n is an integer selected from 1 to 4, and m is an integer selected from 0 to 8. When l is 2 and n is 1, 3, and 4, m is An integer selected from 0 to 8. When l is 2 and n is 2, m is an integer selected from 1 to 8. Also, l is 2, n is 2, and m is 0. for a saccharide substituent R _5a. when multiple units _{exist, R 5, R 5a, l} , m and n have the aforementioned meanings independently for each unit.)
(3) A polyhydroxyalkanoate containing one or more units represented by the chemical formula (6).

(In the formula, l is an integer selected from 1 to 4, n is an integer selected from 1 to 4, and m is an integer selected from 0 to 8. If present, l, m and n represent the above meanings independently for each unit.)
On the other hand, the polyhydroxyalkanoate production method according to the present invention includes the following methods.
(A) A method for producing a polyhydroxyalkanoate represented by the chemical formula (6), comprising polymerizing a compound having a unit represented by the chemical formula (8) in the presence of a catalyst.

(In the formula, l is an integer selected from 1 to 4, n is an integer selected from 1 to 4, and m is an integer selected from 0 to 8.)

(In the formula, l is an integer selected from 1 to 4, n is an integer selected from 1 to 4, and m is an integer selected from 0 to 8. When there are a plurality of units. , L, m and n have the above meanings independently for each unit.)
(B) A method for producing a polyhydroxyalkanoate having a unit represented by the chemical formula (10), which comprises a step of polymerizing the compound represented by the chemical formula (9) in the presence of a catalyst.

(In the formula, R ₉ is a linear or branched alkyl group having 1 to 12 carbon atoms or an aralkyl group. L is an integer selected from 1 to 4, and n is selected from 1 to 4. When n is 1, 3, or 4, n is an integer selected from 1 to 4, and when l is 2, n is 1, 3, or 4.)

(In the formula, R ₁₀ is a linear or branched alkyl group having 1 to 12 carbon atoms or an aralkyl group. L is an integer selected from 1 to 4, and n is selected from 1 to 4. N is an integer selected from 1 to 4 when l is 1, 3, and 4. When l is 2, n is 1, 3, and 4. There are a plurality of units. In this case, l, n and R ₁₀ represent the above meanings independently for each unit.)
(C) A method for producing a polyhydroxyalkanoate containing a unit represented by the chemical formula (11), which comprises a step of oxidizing a double bond portion of the polyhydroxyalkanoate containing a unit represented by the chemical formula (6).

(In the formula, l is an integer selected from 1 to 4, n is an integer selected from 1 to 4, and m is an integer selected from 0 to 8. When there are a plurality of units. , L, m and n have the above meanings independently for each unit.)

(In the formula, R ₁₁ is hydrogen or a group forming a salt. L is an integer selected from 1 to 4, n is an integer selected from 1 to 4, and m is 0 to 0. (It is an integer selected from 8. When there are a plurality of units, l, m, n and R ₁₁ represent the above meanings independently for each unit.)
(D) a unit represented by the chemical formula (12) having a step of hydrolyzing the polyhydroxyalkanoate represented by the unit represented by the chemical formula (10) in the presence of an acid or alkali, or a step of hydrocracking including catalytic reduction. A process for producing a polyhydroxyalkanoate comprising:

(In the formula, R ₁₀ is a linear or branched alkyl group having 1 to 12 carbon atoms or an aralkyl group. L is an integer selected from 1 to 4, and n is selected from 1 to 4. N is an integer selected from 1 to 4 when l is 1, 3, and 4. When l is 2, n is 1, 3, and 4. There are a plurality of units. If you, l, n and R ₁₀ have the aforementioned meanings independently for each unit.)

(In the formula, R ₁₂ is hydrogen or a group forming a salt. L is an integer selected from 1 to 4, n is an integer selected from 1 to 4, and l is 1, In the case of 3, 4, n is an integer selected from 1 to 4. When l is 2, n is 1, 3, 4. When there are a plurality of units, l, n and R ₁₂ are The above meaning is expressed independently for each unit.)
(E) A polyhydroxy containing a unit represented by chemical formula (1) having a step of subjecting a polyhydroxyalkanoate containing a unit represented by chemical formula (11) to at least one amine compound represented by chemical formula (13) to a condensation reaction Method for producing alkanoate.

(In the formula, R ₁₁ is hydrogen or a group forming a salt. L is an integer selected from 1 to 4, n is an integer selected from 1 to 4, and m is 0 to 0. (It is an integer selected from 8. When there are a plurality of units, l, m, n and R ₁₁ represent the above meanings independently for each unit.)

Wherein R ₁₃ is OH, a halogen atom, ONa, OK or OR _13a . R _13a and A ₃ are each independently a substituted or unsubstituted aliphatic hydrocarbon structure, substituted or unsubstituted aromatic When a plurality of units are present, R ₁₃ , R _13a and A ₃ independently represent each of the above-mentioned meanings. .)

(Wherein, R .R ₁ representing a -A ₁ -SO ₂ R ₁ represents OH, a halogen atom, ONa, .R _1a and A ₁ is OK or OR _1a are each independently substituted or unsubstituted Represents a group having an aliphatic hydrocarbon structure, a substituted or unsubstituted aromatic ring structure, or a substituted or unsubstituted heterocyclic structure, wherein l is an integer selected from 1 to 4, and n is 1 to 4 M is an integer selected from 0 to 8. When there are a plurality of units, R, R ₁ , R _1a , A ₁ , l, m, and n are for each unit. Represents the above meaning independently.

  Hereinafter, the present invention will be described in more detail with reference to preferred embodiments. The target polyhydroxyalkanoate represented by the chemical formula (1) in the present invention is a polyhydroxyalkanoate containing a unit represented by the chemical formula (11) used as a starting material and an aminosulfonic acid compound represented by the chemical formula (13). It can be produced by reaction with one species.

(In the formula, R ₁₁ is hydrogen or a group forming a salt. L is an integer selected from 1 to 4, n is an integer selected from 1 to 4, and m is 0 to 0. (It is an integer selected from 8. When there are a plurality of units, l, m, n and R ₁₁ represent the above meanings independently for each unit.)

(A wherein, R ₁₃ is OH, halogen atom, ONa, OK, or OR _13a. Further, R _13a and A ₃ are each independently substituted or unsubstituted aliphatic hydrocarbon structure, a substituted or unsubstituted aromatic Selected from a group having an aromatic ring structure or a substituted or unsubstituted heterocyclic structure (in which R _13a is a monovalent group having a structure selected from these groups, and A ₃ has a structure selected from these groups) A divalent group.) When a plurality of units are present, R ₁₃ , R _13a, and A ₃ represent the above meanings independently for each unit.
More specifically, R ₁₃ is OH, a halogen atom, ONa, OK or OR _13a . R _13a is a linear or branched alkyl group having 1 to 8 carbon atoms, or a substituted or unsubstituted phenyl group. A ₃ is a C _{1 to} C ₈ linear or branched substituted or unsubstituted alkylene group, a substituted or unsubstituted phenylene group, a substituted or unsubstituted naphthalene group, or substituted or unsubstituted N, S, A group having a heterocyclic structure containing any one or more of O is represented. When A ₃ is a ring structure, the unsubstituted ring may be further condensed. Further, when there are a plurality of units, R ₁₃ , R _13a and A ₃ represent the above meanings independently for each unit.

In the case where A ₃ is a linear substituted or unsubstituted alkylene group, an aminosulfonic acid compound represented by the following chemical formula (18) is exemplified.

Wherein R ₁₈ is OH, a halogen atom, ONa, OK or OR _18a . R _18a is a linear or branched alkyl group having 1 to 8 carbon atoms, or a substituted or unsubstituted phenyl group. A ₄ is a C _{1 to} C ₈ linear or branched substituted or unsubstituted alkylene group, and when substituted, an alkyl group having 1 to 20 carbon atoms, An alkoxy group or the like may be substituted.)
Examples of the compound represented by the chemical formula (18) include 2-aminoethanesulfonic acid (taurine), 3-aminopropanesulfonic acid, 4-aminobutanesulfonic acid, 2-amino-2-methylpropanesulfonic acid, and alkali metals thereof. Examples include salts and esterified products.

When A ₃ is a substituted or unsubstituted phenylene group, an aminosulfonic acid compound represented by the following chemical formula (19) is exemplified.

_{(Wherein, R 3a, R 3b, R} 3c, R 3d, R 3e are each independently, SO ₂ R _3f (R _3f represents OH, a halogen atom, ONa, OK, or OR _3f1. (R _3f1 Is a linear or branched alkyl group having 1 to 8 carbon atoms or a substituted or unsubstituted phenyl group.)), Hydrogen atom, halogen atom, alkyl group having 1 to 20 carbon atoms, or 1 to 20 carbon atoms Alkoxy group, OH group, NH ₂ group, NO ₂ group, COOR _3g (R _3g represents any of H atom, Na atom and K atom), acetamide group, OPh group, NHPh group, CF ₃ group, C Represents a ₂ F ₅ group or a C ₃ F ₇ group (Ph represents a phenyl group), and at least one of these groups is SO ₂ R _3f .)
By using the compound represented by the chemical formula (19), a polyhydroxyalkanoate containing at least one unit represented by the chemical formula (3) in the molecule can be obtained.

(In the formula, R _3a , R _3b , R _3c , R _3d , R _3e , l, n and m are defined in the same manner as described above.) The compound represented by the chemical formula (19) is p-aminobenzenesulfone. Acid (sulfanilic acid), m-aminobenzenesulfonic acid, o-aminobenzenesulfonic acid, m-toluidine-4-sulfonic acid, o-toluidine-4-sulfonic acid sodium salt, p-toluidine-2-sulfonic acid, 4 -Methoxyaniline-2-sulfonic acid, o-anisidine-5-sulfonic acid, p-anisidine-3-sulfonic acid, 3-nitroaniline-4-sulfonic acid, 2-nitroaniline-4-sulfonic acid sodium salt, 4 -Nitroaniline-2-sulfonic acid sodium salt, 1,5-dinitroaniline-4-sulfonic acid, 2-aminophenol-4-hydroxy-5-nitroben Sulfonic acid, 2,4-dimethylaniline-5-sulfonic acid sodium salt, 2,4-dimethylaniline-6-sulfonic acid, 3,4-dimethylaniline-5-sulfonic acid, 4-isopropylaniline-6-sulfonic acid 4-trifluoromethylaniline-6-sulfonic acid, 3-carboxy-4-hydroxyaniline-5-sulfonic acid, 4-carboxyaniline-6-sulfonic acid, and alkali metal salts and esterified products thereof.

When A ₃ is a substituted or unsubstituted naphthalene group, an aminosulfonic acid compound represented by the following chemical formula (20A) or chemical formula (20B) is exemplified.

Wherein R _4a , R _4b , R _4c , R _4d , R _4e , R _4f and R _4g are each independently SO ₂ R _4o (R _4o is OH, halogen atom, ONa, OK or OR _4o1 (R _4o1 is a linear or branched alkyl group having 1 to 8 carbon atoms, a substituted or unsubstituted phenyl group)), a hydrogen atom, a halogen atom, an alkyl group having 1 to 20 carbon atoms , C 1-20 alkoxy group, OH group, NH ₂ group, NO ₂ group, COOR _4p (R _4p represents any one of H atom, Na atom and K atom), acetamide group, OPh group, NHPh group CF ₃ group, C ₂ F ₅ group or C ₃ F ₇ group (Ph represents a phenyl group), and at least one of these groups is SO ₂ R _4o .)

_{(Wherein, R 4h, R 4i, R} 4j, R 4k, R 4l, R 4m and R _4n each independently, SO ₂ R _4o (R _4o represents OH, halogen atom, ONa, OK, or OR _4o1 (R _4o1 is a linear or branched alkyl group having 1 to 8 carbon atoms, a substituted or unsubstituted phenyl group)), a hydrogen atom, a halogen atom, an alkyl group having 1 to 20 carbon atoms , C 1-20 alkoxy group, OH group, NH ₂ group, NO ₂ group, COOR _4p (R _4p represents any one of H atom, Na atom and K atom), acetamide group, OPh group, NHPh group CF ₃ group, C ₂ F ₅ group or C ₃ F ₇ group (Ph represents a phenyl group), and at least one of these groups is SO ₂ R _4o .)
By using the compound represented by the chemical formula (20A) or (20B), a polyhydroxyalkanoate containing at least one unit represented by the chemical formula (4A) or (4B) in the molecule can be obtained.

(In the formula, R _4a , R _4b , R _4c , R _4d , R _4e , R _4f , R _4g , l, n and m are defined in the same manner as described above.)

(In the formula, R _4h , R _4i , R _4j , R _4k , R _4l , R _4m , R _4n , l, n and m are defined in the same manner as described above.)
Examples of the compound represented by the chemical formula (20A) or (20B) include 1-naphthylamine-5-sulfonic acid, 1-naphthylamine-4-sulfonic acid, 1-naphthylamine-8-sulfonic acid, and 2-naphthylamine-5-sulfonic acid. 1-naphthylamine-6-sulfonic acid, 1-naphthylamine-7-sulfonic acid, 1-naphthylamine-2-ethoxy-6-sulfonic acid, 1-amino-2-naphthol-4-sulfonic acid, 6-amino-1 Naphthol-3-sulfonic acid, 1-amino-8-naphthol-2,4-sulfonic acid monosodium salt, 1-amino-8-naphthol-3,6-sulfonic acid monosodium salt, etc., sulfonic acid, or its Examples include alkali metal salts and esterified products.

In the case where A ₃ is a group having a heterocyclic structure containing any one or more of substituted or unsubstituted N, S, and O, any of a pyridine ring, a piperazine ring, a furan ring, a thiol ring, etc. as a heterocyclic ring Good. Examples of the compound include 2-aminopyridine-6-sulfonic acid, 2-aminopiperazine-6-sulfonic acid, sulfonic acid, or alkali metal salts and esterified products thereof.

In the case of the sulfonate ester, the group having an ester bond with the sulfonic acid includes, as described above, a substituted or unsubstituted aliphatic hydrocarbon structure, a substituted or unsubstituted aromatic ring structure, a substituted or unsubstituted heterocyclic ring. Examples thereof include a group having a structure. Furthermore, a linear or branched alkyl group having 1 to 8 carbon atoms, a substituted or unsubstituted phenyl group and the like are preferable. From the point of easiness of esterification, OCH ₃ , OC ₂ H ₅ , OC ₆ H ₅ , OC ₃ H ₇ , OC ₄ H ₉ , OCH (CH ₃ ) ₂ , OCH ₂ C (CH ₃ ) ₃ , OC (CH ₃ ) _{3 and the} like are more preferable.

(Method for producing polyhydroxyalkanoate having a unit represented by chemical formula (1))
The reaction of the polyhydroxyalkanoate containing a unit represented by the chemical formula (11) and the aminosulfonic acid compound represented by the chemical formula (13) in the present invention will be described in detail.

  The usage-amount of the compound shown to Chemical formula (13) used for this invention is 0.1-50.0 times mole with respect to the unit shown to Chemical formula (11) used as a starting material, Preferably, it is 1.0-20. The range is 0.0 mole.

  As a method for producing an amide bond from a carboxylic acid and an amine of the present invention, there is a condensation reaction by heat dehydration. In particular, from the viewpoint of mild reaction conditions in which the ester bond of the polymer main chain is not cleaved, it is effective to activate the carboxylic acid moiety with an activator to produce an active acyl intermediate and then react with the amine. It is. Examples of the active acyl intermediate include an acid halide, an acid anhydride, and an active ester. In particular, a method of forming an amide bond in the same reaction field using a condensing agent is preferable from the viewpoint of simplifying the production process. If necessary, it can be isolated as an acid halide and then subjected to a condensation reaction with an amine.

  As the condensing agent to be used, a phosphoric acid condensing agent used for polycondensation of aromatic polyamide, a carbodiimide condensing agent used for peptide synthesis, an acid chloride condensing agent and the like are represented by chemical formulas (13) and (11). It is possible to select appropriately depending on the combination of the compounds.

Examples of the phosphoric acid-based condensing agent include a phosphite-based condensing agent, a phosphoric chloride-based condensing agent, a phosphoric anhydride-based condensing agent, a phosphoric ester-based condensing agent, and a phosphoric acid amide-based condensing agent.
In the reaction of the present invention, a condensing agent such as phosphite can be used. Phosphites used at this time include triphenyl phosphite, diphenyl phosphite, tri-o-tolyl phosphite, di-o-tolyl phosphite, tri-m-tolyl phosphite , Di-m-tolyl phosphite, tri-p-tolyl phosphite, di-p-tolyl phosphite, di-o-chlorophenyl phosphite, tri-p-chlorophenyl phosphite, diphosphite -P-chlorophenyl, trimethyl phosphite, triethyl phosphite and the like. Of these, triphenyl phosphite is preferably used. In order to improve the solubility and reactivity of the polymer, a metal salt such as lithium chloride or calcium chloride may be added.

  Examples of the carbodiimide condensing agent include dicyclohexylcarbodiimide (DCC), N-ethyl-N′-3-dimethylaminopropylcarbodiimide (EDC = WSCI), diisopropylcarbodiimide (DIPC), and the like. In combination with DCC or WSCI and N-hydroxysuccinimide (HONSu), 1-hydroxybenzotriazole (HOBt), or 3-hydroxy-4-oxo-3,4-dihydro-1,2,3-benzotriazine (HOObt) It may be used.

  The usage-amount of a condensing agent is 0.1-50 times mole with respect to the unit shown to Chemical formula (11), Preferably, it is the range of 1-20 times mole.

  In the reaction of the present invention, a solvent can be used as necessary. Solvents used include hydrocarbons such as hexane, cyclohexane and heptane, ketones such as acetone and methyl ethyl ketone, ethers such as dimethyl ether, diethyl ether and tetrahydrofuran, dichloromethane, chloroform, carbon tetrachloride, dichloroethane, trichloroethane and the like. Halogenated hydrocarbons, aromatic hydrocarbons such as benzene and toluene, aprotic polar solvents such as N, N-dimethylformamide, dimethyl sulfoxide, dimethylacetamide and hexamethylphosphoramide, and pyridine derivatives such as pyridine and picoline , N-methylpyrrolidone and the like. Particularly preferably, pyridine, N-methylpyrrolidone or the like is used. The amount of the solvent used can be appropriately determined according to the starting material, the type of base, reaction conditions and the like. In the method of the present invention, the reaction temperature is not particularly limited, but is usually a temperature in the range of −20 ° C. to the boiling point of the solvent. However, it is desirable to carry out the reaction at an optimum temperature according to the condensing agent used.

  In the method of the present invention, the reaction time is usually in the range of 1 to 48 hours. In particular, 1 to 10 hours are preferable.

  In the present invention, recovery and purification of the desired polyhydroxyalkanoate from the reaction solution containing the polyhydroxyalkanoate having the unit represented by the chemical formula (1) thus produced can be performed by distillation, which is a conventional method. It is. Alternatively, water, alcohols such as methanol and ethanol, and solvents such as dimethyl ether, diethyl ether, tetrahydrofuran and other ethers are uniformly mixed with the reaction solution to precipitate the desired polyhydroxyalkanoate represented by the chemical formula (1). This can be recovered. The polyhydroxyalkanoate having a unit represented by the chemical formula (1) obtained here can be isolated and purified if necessary. The isolation and purification method is not particularly limited, and a reprecipitation method using a solvent insoluble in the polyhydroxyalkanoate having the unit represented by the chemical formula (1), a column chromatography method, a dialysis method, etc. Can do.

As another production method of the present invention, when the R moiety in the chemical formula (1) is —A ₁ —SO ₃ H, a methyl esterifying agent is used after the condensation reaction with the amine to form the R moiety in the chemical formula (1). There is a method of carrying out methyl esterification in which -A ₁ —SO ₃ CH ₃ is used. As the methyl esterifying agent, those used for methyl esterification of fatty acids in gas chromatography analysis can be used. As the methyl esterification method, acid catalyst methods such as hydrochloric acid-methanol method, boron trifluoride-methanol method, sulfuric acid-methanol method are sodium methoxide method, tetramethylguanidine method, trimethyllsilyldiazomethane method, etc. Law. Among them, the trimethylsilyldiazomethane method is preferable because methylation can be performed under mild conditions.

  Solvents used in the reaction of the present invention are hydrocarbons such as hexane, cyclohexane and heptane, alcohols such as methanol and ethanol, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane and trichloroethane, Examples thereof include aromatic hydrocarbons such as benzene and toluene. Particularly preferably, halogenated hydrocarbons are used. The amount of the solvent used can be appropriately determined according to the starting materials, reaction conditions and the like. In the method of the present invention, the reaction temperature is not particularly limited, but is usually a temperature in the range of -20 to 30 ° C. However, it is desirable to carry out the reaction at an optimum temperature according to the condensing agent and reagent to be used.

  On the other hand, in the polyhydroxyalkanoate having a unit represented by the chemical formula (5) of the present invention, the polyhydroxyalkanoate having a unit represented by the chemical formula (21) is a polyhydroxyalkanoate having a unit represented by the chemical formula (22) as a starting material. And a method of oxidizing the side chain double bond portion of the polyhydroxyalkanoate.

(In the formula, R ₂₁ is hydrogen or a group forming a salt. L is an integer selected from 1 to 4, n is an integer selected from 1 to 4, and m is , An integer selected from 0 to 8, when l is 1, 3, or 4, n is an integer selected from 1 to 4, and m is an integer selected from 0 to 8. When l is 2 and n is 1, 3, or 4, m is an integer selected from 0 to 8. When l is 2 and n is 2, m is selected from 1 to 8. When there are a plurality of units, R ₂₁ , l, m and n have the above meanings independently for each unit.)

(In the formula, l is an integer selected from 1 to 4, n is an integer selected from 1 to 4, m is an integer selected from 0 to 8, and l is 1, In the case of 3, 4, n is an integer selected from 1 to 4, and m is an integer selected from 0 to 8. When l is 2, and n is 1, 3, 4, m Is an integer selected from 0 to 8. When l is 2 and n is 2, m is an integer selected from 1 to 8. When there are a plurality of units, l, m and n represents the above meaning independently for each unit.)
As a method for obtaining a carboxylic acid by oxidative cleavage of a carbon-carbon double bond as described above with an oxidizing agent, for example, a method using permanganate (J. Chem. Soc., Perkin. Trans. 1,806 (1973)), a method using dichromate (Org. Synth., 4, 698 (1963)), a method using periodate (J. Org. Chem., 46, 19 (1981)). ) A method using nitric acid (Japanese Laid-Open Patent Publication No. 59-190945), a method using ozone (J. Am. Chem. Soc., 81, 4273 (1959)) and the like are known, and Macromolecular chemistry, 4 , 289-293 (2001) oxidized the carbon-carbon double bond at the end of the side chain of polyhydroxyalkanoate produced by microorganisms. A method for obtaining carboxylic acid by using potassium permanganate as an agent and carrying out the reaction under acidic conditions has been reported. In the present invention, a similar method can be used.

  As the permanganate used as the oxidizing agent, potassium permanganate is common. Since the oxidative cleavage reaction is a stoichiometric reaction, the amount of permanganate used is usually 1 molar equivalent or more, preferably 2 to 10 molar equivalents per 1 mol of the unit represented by the chemical formula (22). It is good to do. In order to bring the reaction system to acidic conditions, various inorganic acids and organic acids such as sulfuric acid, hydrochloric acid, acetic acid and nitric acid are usually used. However, when an acid such as sulfuric acid, nitric acid or hydrochloric acid is used, the ester bond in the main chain is cleaved, which may cause a decrease in molecular weight. Therefore, it is preferable to use acetic acid. The amount of the acid used is usually 0.2 to 2000 molar equivalents, preferably 0.4 to 1000 molar equivalents per 1 mol of the unit represented by the chemical formula (22). If it is 0.2 molar equivalent or more, it becomes a preferable yield, and if it is 2000 molar equivalent or less, it is possible to reduce the by-product of the decomposition product due to the acid, so it is preferably within the above range. In addition, crown-ether can be used for the purpose of promoting the reaction. In this case, the crown-ether and the permanganate form a complex, and the effect of increasing the reaction activity is obtained. As the crown-ether, dibenzo-18-crown-6-ether, dicyclo-18-crown-6-ether, or 18-crown-6-ether is generally used. The amount of the crown-ether used is usually 0.005 to 2.0 molar equivalents, preferably 0.01 to 1.5 molar equivalents per mole of permanganate.

  In addition, the solvent in the oxidation reaction of the present invention is not particularly limited as long as it is an inert solvent. For example, water, acetone; ethers such as tetrahydrofuran and dioxane; aromatic hydrocarbons such as benzene; hexane And aliphatic hydrocarbons such as heptane; halogenated hydrocarbons such as methyl chloride, dichloromethane, and chloroform. Among these solvents, halogenated hydrocarbons such as methyl chloride, dichloromethane, chloroform, and acetone are preferable in consideration of the solubility of polyhydroxyalkanoate.

  In the oxidation reaction of the present invention, the polyhydroxyalkanoate containing the unit represented by the chemical formula (22), the permanganate and the acid may be charged together with the solvent from the beginning and reacted, and each of them may be continuously or intermittently used. You may make it react, adding in the system. Alternatively, only permanganate may be dissolved or suspended in a solvent first, and then polyhydroxyalkanoate and acid may be continuously or intermittently added to the system to react. Alternatively, only permanganate and an acid may be added to the system continuously or intermittently and reacted in advance. Furthermore, polyhydroxyalkanoate and acid may be charged first, and then permanganate may be added to the system continuously or intermittently to react, and the permanganate and acid are charged first. The polyhydroxyalkanoate may be continuously or intermittently added to the system and allowed to react, and the polyhydroxyalkanoate and permanganate are charged first, followed by the acid continuously or intermittently. The reaction may be carried out in addition to the system.

  The reaction temperature is usually −40 to 40 ° C., preferably −10 to 30 ° C. The reaction time depends on the stoichiometric ratio between the unit represented by the chemical formula (22) and the permanganate and the reaction temperature, but is usually preferably 2 to 48 hours.

  A polyhydroxyalkanoate containing a unit represented by the chemical formula (24) is produced from the polyhydroxyalkanoate containing a unit represented by the chemical formula (23) shown in the present invention by an oxidation reaction in the same manner as the oxidation reaction described above. be able to. This manufacturing method is a novel manufacturing method.

(In the formula, l is 2, n is 2, and m is 0.)

(In the formula, R ₂₄ is hydrogen or a group forming a salt. L is 2, n is 2, and m is 0.)
Further, in the polyhydroxyalkanoate having the unit represented by the chemical formula (5), the polyhydroxyalkanoate having the unit represented by the chemical formula (12) is obtained by using the polyhydroxyalkanoate having the unit represented by the chemical formula (10) as a starting material. It can be produced by a method of hydrolyzing the side chain ester moiety in the presence of an acid or alkali, or a method of hydrocracking including catalytic reduction.

(In the formula, R ₁₂ is hydrogen or a group forming a salt. L is an integer selected from 1 to 4, n is an integer selected from 1 to 4, and l is 1, 3; in the case of 4, n If it .l is 2 an integer selected from 1 to 4, n is 1,3,4. when multiple units exist, l, n and R _12, (The above meaning is expressed independently for each unit.)

(In the formula, R ₁₀ is a linear or branched alkyl group having 1 to 12 carbon atoms or an aralkyl group. L is an integer selected from 1 to 4, and n is selected from 1 to 4. N is an integer selected from 1 to 4 when l is 1, 3, and 4. When l is 2, n is 1, 3, and 4. There are a plurality of units. In this case, l, n and R ₁₀ represent the above meanings independently for each unit.)
When using the method of hydrolysis in the presence of acid or alkali, hydrochloric acid, sulfuric acid, nitric acid in water or water-affinity organic solvents such as methanol, ethanol, tetrahydrofuran, dioxane, dimethylformamide, dimethyl sulfoxide as a solvent. Or an aqueous solution of an inorganic acid such as phosphoric acid or an organic acid such as trifluoroacetic acid, trichloroacetic acid, p-toluenesulfonic acid, methanesulfonic acid, or an aqueous caustic alkali such as sodium hydroxide or potassium hydroxide, This method can be performed using an aqueous solution of an alkali carbonate such as sodium carbonate or potassium carbonate, or an alcohol solution of a metal alkoxide such as sodium methoxide or sodium ethoxide. The reaction temperature is usually 0 to 40 ° C, preferably 0 to 30 ° C. The reaction time is usually 0.5 to 48 hours. However, when hydrolyzed with an acid or alkali, the ester bond of the main chain may be cleaved in any case, and a decrease in molecular weight may be observed.

  When using the method of obtaining carboxylic acid using the method of hydrocracking including catalytic reduction, it is performed as follows. That is, in an appropriate solvent, catalytic reduction is carried out by allowing hydrogen to act at normal pressure or under pressure in the presence of a reduction catalyst at a temperature in the range of -20 ° C to the boiling point of the solvent used, preferably 0 to 50 ° C. Do it. Examples of the solvent used include water, methanol, ethanol, propanol, hexafluoroisopropanol, ethyl acetate, diethyl ether, tetrahydrofuran, dioxane, benzene, toluene, dimethylformamide, pyridine, and N-methylpyrrolidone. A mixed solvent of these solvents can also be used. As the reduction catalyst, a catalyst such as palladium, platinum, rhodium or the like supported on a carrier or Raney nickel is used. The reaction time is usually preferably 0.5 to 72 hours. The reaction solution containing the polyhydroxyalkanoate having the unit represented by the chemical formula (10) thus produced is recovered as a crude polymer by removing the catalyst by filtration and removing the solvent by distillation or the like. The polyhydroxyalkanoate having a unit represented by the chemical formula (10) obtained here can be isolated and purified if necessary. The isolation and purification method is not particularly limited, and a method in which a polyhydroxyalkanoate having a unit represented by the chemical formula (10) is precipitated using a solvent insoluble, a column chromatography method, a dialysis method, or the like may be used. it can. However, even when catalytic reduction is used, the ester bond of the main chain is also cleaved, and a decrease in molecular weight may be observed.

  Further, in the polyhydroxyalkanoate having a unit represented by the chemical formula (5) of the present invention, the polyhydroxyalkanoate having a unit represented by the chemical formula (25) is a polyhydroxyalkanoate having a unit represented by the chemical formula (11) as a starting material. The alkanoate can be produced by esterification using an esterifying agent.

(Wherein R _25a is a linear or branched alkyl group having 1 to 12 carbon atoms, an aralkyl group, or a substituent having a saccharide. L is an integer selected from 1 to 4; Is an integer selected from 1 to 4, m is an integer selected from 0 to 8, and when l is 1, 3, or 4, n is an integer selected from 1 to 4. , M is an integer selected from 0 to 8. When l is 2 and n is 1, 3, or 4, m is an integer selected from 0 to 8. l is 2, n When m is 2, m is an integer selected from 1 to 8. When l is 2, n is 2, and m is 0, R _25a is a substituent having a saccharide. When units are present, R _25a , l, m and n have the above meanings independently for each unit.)

(In the formula, R ₁₁ is hydrogen or a group forming a salt. L is an integer selected from 1 to 4, n is an integer selected from 1 to 4, and m is 0 to 0. (It is an integer selected from 8. When there are a plurality of units, l, m, n and R ₁₁ represent the above meanings independently for each unit.)
As the esterifying agent used, diazomethane and DMF dimethylacetals can be used. For example, polyhydroxyalkanoate having a unit represented by the chemical formula (11) is trimethylsilyldiazomethane, DMF dimethyl acetal, DMF diethyl acetal, DMF dipropyl acetal, DMF diisopropyl acetal, DMF-n-butyl acetal, DMF-tert-butyl. Reacts easily with acetal or DMF dineopentyl acetal to give the corresponding ester. Alcohols such as methanol, ethanol, propanol, isopropyl alcohol, butyl alcohol, sec-butyl alcohol, tert-butyl alcohol, pentyl alcohol, neopentyl alcohol, hexyl alcohol, heptyl alcohol, octyl alcohol, nonyl alcohol, decyl alcohol , A reaction using a saccharide for introducing a group having a sugar structure such as lauryl alcohol, for example, D-glucose, D-fructose, other saccharides, etc., using an acid catalyst or a condensing agent such as DCC To obtain an esterified polyhydroxyalkanoate.

  The polyhydroxyalkanoate represented by the chemical formula (6) of the present invention can be produced by polymerizing the intramolecular cyclized compound of ω-hydroxycarboxylic acid represented by the chemical formula (8) in the presence of a catalyst.

(In the formula, l is an integer selected from 1 to 4, n is an integer selected from 1 to 4, and m is an integer selected from 0 to 8. When there are a plurality of units. , L, m and n have the above meanings independently for each unit.)

(In the formula, l is an integer selected from 1 to 4, n is an integer selected from 1 to 4, and m is an integer selected from 0 to 8.)
In the production of the polyester containing the unit represented by the chemical formula (6) using the chemical formula (8) which is the intramolecular ring-closing compound of the ω-hydroxycarboxylic acid of the present invention, the polymerization method is not particularly limited. A polymerization method, a slurry polymerization method, a bulk polymerization method, or the like can be adopted. When a polymerization solvent is used, the solvent is not particularly limited. For example, an inert solvent such as an aliphatic hydrocarbon having 5 to 18 carbon atoms or a cyclic hydrocarbon, or an aromatic hydrocarbon having 6 to 20 carbon atoms, Tetrahydrofuran, chloroform, orthodichlorobenzene, dioxane and the like can be used. As a catalyst used for this polymerization, a known ring-opening polymerization catalyst can be used. Examples include tin dichloride, tin tetrachloride, stannous fluoride, stannous acetate, stannous stearate, stannous octoate, stannous oxide, stannic oxide, and other tin salts. . Also, triethoxyaluminum, tri-n-propoxy-aluminum, tri-iso-propoxyaluminum, tri-n-butoxyaluminum, tri-iso-butoxyaluminum, aluminum chloride, di-iso-propylzinc, dimethylzinc, diethyl Zinc, zinc chloride, tetra-n-propoxy titanium, tetra-n-butoxy titanium, tetra-n-butoxy titanium, tetra-t-butoxy titanium, antimony trifluoride, lead oxide, lead stearate, titanium tetrachloride, three Examples thereof include boron fluoride, boron trifluoride ether complex, triethylamine, and tributylamine.

  The amount of these catalysts used is in the range of 0.0001 to 10% by weight, more preferably in the range of 0.001 to 5% by weight, based on the total amount of monomer compounds.

  In the present invention, a known polymerization initiator can be used as a polymerization initiator in the ring-opening polymerization. Specifically, the aliphatic alcohol may be mono-, di- or polyhydric alcohol, and may be saturated or unsaturated. Specifically, monoalcohols such as methanol, ethanol, propanol, butanol, pentanol, hexanol, heptanol, nonanol, decanol, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, p-tert-butylbenzyl alcohol, ethylene glycol, Dialcohols such as butanediol, hexanediol, nonanediol, and tetramethylene glycol, polyhydric alcohols such as glycerol, sorbitol, xylitol, ribitol, and erythritol, and methyl lactate and ethyl lactate can be used. These aliphatic alcohols are used in a proportion of 0.01 to 10% by weight based on the total amount of monomers, although there are some differences depending on the conditions such as the type of alcohol used. In the present invention, the ring-opening polymerization reaction temperature is in the range of 25 to 200 ° C, preferably 50 to 200 ° C, more preferably 100 to 180 ° C.

  In the present invention, the ring-opening polymerization reaction may be carried out under an inert atmosphere such as nitrogen or argon, or under reduced pressure or under pressure. In this case, a catalyst and alcohol may be added successively.

  The polyhydroxyalkanoate having a unit represented by the chemical formula (10) of the present invention can be produced by polymerizing an intramolecular ring-closed compound of ω-hydroxycarboxylic acid represented by the chemical formula (9) in the presence of a catalyst. .

(In the formula, R ₉ is a linear or branched alkyl group having 1 to 12 carbon atoms or an aralkyl group. L is an integer selected from 1 to 4, and n is selected from 1 to 4. (When l is 1, 3, or 4, n is an integer selected from 1 to 4, and when l is 2, n is 1, 3, or 4.)

(In the formula, R ₁₀ is a linear or branched alkyl group having 1 to 12 carbon atoms or an aralkyl group. L is an integer selected from 1 to 4, and n is selected from 1 to 4. When l is 1, 3, and 4, n is an integer selected from 1 to 4. When l is 2, n is 1, 3, and 4. There are a plurality of units. In this case, l and n represent the above meanings independently for each unit.)
In the production of the polyester containing the unit represented by the chemical formula (10) using the chemical formula (9) which is the intramolecular ring-closing compound of the ω-hydroxycarboxylic acid of the present invention, the polymerization method is not particularly limited. A polymerization method, a slurry polymerization method, a bulk polymerization method, or the like can be adopted. When a polymerization solvent is used, the solvent is not particularly limited. For example, an inert solvent such as an aliphatic hydrocarbon having 5 to 18 carbon atoms or a cyclic hydrocarbon, or an aromatic hydrocarbon having 6 to 20 carbon atoms, Tetrahydrofuran, chloroform, orthodichlorobenzene, dioxane and the like can be used.

  In the present invention, a known ring-opening polymerization catalyst can be used as the catalyst used for the polymerization. Examples include tin dichloride, tin tetrachloride, stannous fluoride, stannous acetate, stannous stearate, stannous octoate, stannous oxide, stannic oxide, and other tin salts. . Also, triethoxyaluminum, tri-n-propoxy-aluminum, tri-iso-propoxyaluminum, tri-n-butoxyaluminum, tri-iso-butoxyaluminum, aluminum chloride, di-iso-propylzinc, dimethylzinc, diethyl Zinc, zinc chloride, tetra-n-propoxy titanium, tetra-n-butoxy titanium, tetra-n-butoxy titanium, tetra-t-butoxy titanium, antimony trifluoride, lead oxide, lead stearate, titanium tetrachloride, three Examples thereof include boron fluoride, boron trifluoride ether complex, triethylamine, and tributylamine.

  The amount of these catalysts used is in the range of 0.0001 to 10% by weight, more preferably in the range of 0.001 to 5% by weight, based on the total amount of monomer compounds.

  In the present invention, a known polymerization initiator can be used as a polymerization initiator in the ring-opening polymerization. Specifically, the aliphatic alcohol may be mono-, di- or polyhydric alcohol, and may be saturated or unsaturated. Specifically, monoalcohols such as methanol, ethanol, propanol, butanol, pentanol, hexanol, heptanol, nonanol, decanol, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, p-tert-butylbenzyl alcohol, ethylene glycol, Dialcohols such as butanediol, hexanediol, nonanediol, and tetramethylene glycol, polyhydric alcohols such as glycerol, sorbitol, xylitol, ribitol, and erythritol, and methyl lactate and ethyl lactate can be used. These aliphatic alcohols are used in a proportion of 0.01 to 10% by weight based on the total amount of monomers, although there are some differences depending on the conditions such as the type of alcohol used. In the present invention, the ring-opening polymerization reaction temperature is in the range of 25 to 200 ° C, preferably 50 to 200 ° C, more preferably 100 to 180 ° C.

  In the present invention, the ring-opening polymerization reaction may be carried out under an inert atmosphere such as nitrogen or argon, or under reduced pressure or under pressure. In this case, a catalyst and alcohol may be added successively.

  The polyhydroxyalkanoate according to the present invention is mainly composed of the unit represented by the chemical formula (1), (5) or (6) described above, but is used for changing various physical properties such as mechanical characteristics and decomposition characteristics. Further, a copolymer obtained by copolymerizing the second component or the like may be used. For example, a unit represented by the chemical formula (7) can be further contained in the molecule.

(R ₇ is a linear or branched alkylene group having 1 to 11 carbon atoms, an alkyleneoxyalkylene group (each alkylene group is independently an alkylene group having 1 to 2 carbon atoms) or aryl. (Alkylidene group having 1 to 5 carbon atoms which may be used. When there are a plurality of units, R ₇ represents the above meaning independently for each unit.)
As specific examples of the second component, cyclic diesters of α-hydroxycarboxylic acid and lactones which are intramolecular cyclized compounds of ω-hydroxycarboxylic acid can be copolymerized. Furthermore, specific examples of cyclic diesters of α-hydroxycarboxylic acid include glycolic acid, lactic acid, α-hydroxybutyric acid, α-hydroxyisobutyric acid, α-hydroxyvaleric acid, α-hydroxyisovaleric acid, α-hydroxy- Examples include intermolecular cyclic diesters such as α-methylbutyric acid, α-hydroxycaproic acid, α-hydroxyisocaproic acid, α-hydroxy-β-methylvaleric acid, α-hydroxyheptanoic acid, mandelic acid, β-phenyllactic acid and the like. . Moreover, what has asymmetric carbon may be any of L-form, D-form, racemic form, and meso form. In addition, the cyclic diester may be formed by different α-oxyacid molecules. Specifically, it is a cyclic diester between glycolic acid and lactic acid, such as 3-methyl-2,5-diketo-1,4-dioxane. In addition, lactones which are intramolecular ring-closing compounds of ω-hydroxycarboxylic acid include β-propiolactone, β-butyrolactone, β-isovalerolactone, β-caprolactone, β-isocaprolactone, β-methyl-β- Intramolecular ring-closing compounds such as valerolactone, γ-butyrolactone, γ-valerolactone, δ-valerolactone, δ-caprolactone, 11-oxydecanoic acid lactone, p-dioxanone, 1,5-dioxepan-2-one and the like can be mentioned. It is not limited to these.

    The number average molecular weight of the polyhydroxyalkanoate obtained by the polymerization can be obtained with various molecular weights by changing conditions such as the type and amount of the polymerization catalyst, the polymerization temperature, and the polymerization time, but is preferably 1,000 to 1,000,000.

  The molecular weight of the polyhydroxyalkanoate can be measured as a relative molecular weight or an absolute molecular weight. It can be easily measured by, for example, GPC (gel permeation chromatography). As a specific GPC measurement method, the polyhydroxyalkanoate is dissolved in a soluble solvent in advance, and measurement is performed with the same mobile phase. As a detector, it can use according to the polyhydroxyalkanoate to measure, such as a differential refraction detector (RI) or an ultraviolet detector (UV). The molecular weight is determined as a relative comparison with a sample (polystyrene, polymethyl methacrylate, etc.). The solvent may be selected from those in which the polymer is soluble, such as dimethylformamide (DMF), dimethyl sulfoxide (DMSO), chloroform, tetrahydrofuran (THF), toluene, hexafluoroisopropanol (HFIP). In the case of a polar solvent, it can also be measured by adding a salt.

Moreover, in this invention, the ratio (Mw / Mn) of the weight average molecular weight (Mw) measured as mentioned above and a number average molecular weight (Mn) is in the range of 1-10, The said polyhydroxyalkanoate Is preferably used.
The reaction solvent, reaction temperature, reaction time, purification method, etc. in the chemical reaction of the present invention are not limited to the above methods.

  The present invention will be described in more detail with reference to the following examples. However, the method of the present invention is not limited to these examples. First, the materials used in the examples are shown as adjustment examples.

(Preparation example)
The raw materials used in the examples can be prepared by the following method.
(Preparation Example 1)
Production method of tetrahydro-4- (2-propenyl) -2H-pyran-2-one represented by chemical formula (26) described in Examples 1-4:
Tetrahydro-4- (2-propenyl) -2H-pyran-2-one represented by the chemical formula (26) described in Examples 1 to 4 is a method described in Journal of American Chemical Society 2002,124,13171-13718. It can manufacture by using (the compound (15) in literature).

  In an eggplant flask, 122 ml (244.0 mmol) of a 2M allylmagnesium chloride-THF solution was added, and 500 ml of THF in which 27.5 g (122.1 mmol) of zinc bromide was dissolved was added thereto, followed by stirring at 0 ° C. This was placed under a nitrogen atmosphere and stirred at -78 ° C. Next, 53.0 g (487.8 mmol) of chlorotrimethylsilane was added, and 200 ml of a THF solution in which 10.0 g (101.9 mmol) of 3,4-dihydro-2H-pyran-2-one was dissolved was slowly added. The mixture was stirred at -78 ° C for 1 hour. After completion of the reaction, 1N-hydrochloric acid was added to the reaction solution, and then diethyl ether was added to extract the organic layer. After washing three times with 1N hydrochloric acid, the organic layer was recovered. The collected organic layer was dried over anhydrous sodium sulfate. After removing sodium sulfate, the solution was evaporated to recover crude tetrahydro-4- (2-propenyl) -2H-pyran-2-one. Next, it refine | purified by silica gel column chromatography, and 7.10g of the target tetrahydro-4- (2-propenyl) -2H-pyran-2-one was obtained by drying under reduced pressure. In order to specify the structure of the obtained compound, NMR analysis was performed under the following conditions.

<Measurement equipment> FT-NMR: Bruker DPX400
Resonance frequency: ¹ H = 400 MHz
<Measurement conditions> Measurement nuclide: ¹ H
Solvent used: CDCl ₃
Measurement temperature: room temperature As a result, it was confirmed that the obtained compound was the target tetrahydro-4- (2-propenyl) -2H-pyran-2-one.

(Preparation Example 2)
Production method of tetrahydro-4- (3-butenyl) -2H-pyran-2-one described in chemical formula (31) described in Example 5:
The target tetrahydro-4- (3 was prepared in the same manner as in Example 1 except that 122 ml (244.0 mmol) of 2M 3-butenylmagnesium bromide-THF solution was used instead of allylmagnesium chloride described in Preparation Example 1. -Butenyl) -2H-pyran-2-one 7.40g was obtained.
(Preparation Example 3)
Method for producing 5- (2-propenyl) -2-oxepanone described in Chemical Formula (33) described in Example 6:
5- (2-propenyl) -2-oxepanone represented by the chemical formula (33) described in Example 6 is a known compound, for example, a method described in Journal of American Chemical Society 1998, 120, 3541-3548 ( It can be obtained by using the compound (6e) in the literature.
(Preparation Example 4)
Method for producing 7-oxo-4-oxepanecarboxylic acid phenylmethyl ester described in chemical formula (38) described in Example 8:
The 7-oxo-4-oxepanecarboxylic acid phenylmethyl ester represented by the chemical formula (38) described in Example 8 uses the method described in Macromolecules, 2000, 33, 4622 (compound (12) in the literature). Can be obtained. More specifically, the target product can be obtained by a four-step reaction.
(Reaction 1)
To 280 ml of a methylene chloride suspension containing 40.0 g (185.6 mmol) of pyridinium chlorochromate was added 25 ml of a methylene chloride solution of 30.0 g (174.2 mmol) of ethyl 4-hydroxycyclohexanecarboxylate, and the mixture was stirred at room temperature for 2 hours. The mixture was stirred and then stirred at 45 ° C. for 5 hours. After completion of the reaction, the reaction solution was decanted and the residue was rinsed with diethyl ether. The reaction solution and rinsed diethyl ether were combined together and purified by silica gel column chromatography, followed by distillation under reduced pressure to obtain 29.5 g of ethyl 4-ketocyclohexanecarboxylate.
(Reaction 2)
2% sulfuric acid was added to 20.0 g (117.5 mmol) of ethyl 4-ketocyclohexanecarboxylate, and the mixture was stirred at 115 ° C. for 4 hours. After completion of the reaction, the mixture was extracted with diethyl ether and dried with magnesium sulfate. After distilling off the solvent, a crude product was obtained. The crude product was distilled under reduced pressure to obtain 13.5 g of ethyl 4-ketocyclohexanecarboxylate.
(Reaction 3)
In an acetone solution containing 12.0 g (84.4 mmol) of 4-ketocyclohexanecarboxylic acid and 4.7 g (33.8 mmol) of potassium carbonate, 17.3 g (101.3 mmol) of benzyl bromide was added at room temperature. Next, this was stirred at 60 ° C. for 3 hours. After completion of the reaction, potassium carbonate was removed by filtration, and acetone was distilled off to obtain a crude product. The crude product was purified by silica gel column chromatography to obtain 16.5 g of 4-ketocyclohexanecarboxylic acid phenylmethyl ester.
(Reaction 4)
A chloroform solution containing metachloroperbenzoic acid was added to a chloroform solution containing 16.5 g (71.0 mmol) of benzyl 4-ketocyclohexanecarboxylate at room temperature. This was stirred at 65 ° C. for 2 hours. After completion of the reaction, the mixture was filtered using celite, and then an aqueous sodium hydrogen carbonate solution was added to separate the layers. After collecting the organic layer, it was dried over sodium sulfate. After distilling off the solvent, purification was performed by silica gel column chromatography, followed by distillation under reduced pressure, whereby 7-oxo-4-oxepanecarboxylic acid phenylmethyl ester represented by the chemical formula (38) as the target product was obtained. 14.7 g was obtained. In order to specify the structure of the obtained compound, NMR analysis was performed under the same conditions as in Preparation Example 1. As a result, 7-oxo-4-oxepanecarboxylic acid phenylmethyl ester represented by the chemical formula (38) as the target product was obtained. It was confirmed that.

(Preparation Example 5)
Method for producing 7-oxo-3-oxepanecarboxylic acid phenylmethyl ester represented by the chemical formula (35) described in Example 7:
7-Oxo-3-oxepanecarboxylic acid phenylmethyl ester represented by the chemical formula (35) described in Example 7 can be produced by using the method described in Preparation Example 4. Specifically, by using 3-ketocyclohexanecarboxylic acid instead of 4-ketocyclohexanecarboxylic acid in (Reaction 3) in Preparation Example 4, (Reaction 3) and (Reaction 4) are similarly performed.
The object can be obtained. The chemical formula which is the target product by carrying out the same method as in Preparation Example 4 except that 12.0 g (84.4 mmol) of 3-ketocyclohexanecarboxylic acid is used instead of 4-ketocyclohexanecarboxylic acid in Preparation Example 4. 6.0 g of 7-oxo-3-oxepanecarboxylic acid phenylmethyl ester represented by (35) was obtained.

(Preparation Example 6)
Production method of tetrahydro-6-oxo-2H-pyran-3-carboxylic acid phenylmethyl ester represented by the chemical formula (41) described in Example 9 Tetrahydro-6-6 represented by the chemical formula (41) described in Example 9 Oxo-2H-pyran-3-carboxylic acid phenylmethyl ester can be produced by using the method described in Preparation Example 4. Specifically, in (Reaction 3) in Preparation Example 4 using 3-ketocyclopentanecarboxylic acid instead of 4-ketocyclohexanecarboxylic acid, (Reaction 3) and (Reaction 4) are performed in the same manner. Can be obtained. The chemical formula which is the target product by carrying out the same method as in Preparation Example 4 except that 10.8 g (84.4 mmol) of 3-ketocyclopentanecarboxylic acid is used instead of 4-ketocyclohexanecarboxylic acid in Preparation Example 4. 4.5 g of tetrahydro-6-oxo-2H-pyran-3-carboxylic acid phenylmethyl ester represented by (35) was obtained.

Specific examples are shown below.
(Example 1)
[Polyester synthesis using tetrahydro-4- (2-propenyl) -2H-pyran-2-one represented by chemical formula (26)]

Tetrahydro-4- (2-propenyl) -2H-pyran-2-one represented by chemical formula (26) 1.40 g (0.01 mmol), 0.01M tin octylate (tin 2-ethylhexanoate) in toluene 4.0 ml of a solution, 4.0 ml of 0.01 M p-tert-butylbenzyl alcohol in toluene was charged into a polymerization ampule, dried under reduced pressure for 1 hour and purged with nitrogen, and then sealed under reduced pressure. It heated to 150 degreeC and ring-opening polymerization was performed. The reaction was terminated after 12 hours and cooled. The obtained polymer was dissolved in chloroform and reprecipitated in 10 times the amount of chloroform required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 0.53 g of polymer. In order to specify the structure of the obtained polymer, NMR analysis was performed under the following conditions.
<Measurement equipment> FT-NMR: Bruker DPX400
Resonance frequency: ¹ H = 400 MHz
<Measurement conditions> Measurement nuclide: ¹ H
Solvent used: TMS / CDCl ₃
Measurement temperature: room temperature As a result, it was confirmed to be a polyhydroxyalkanoate composed of units represented by the following chemical formula (27).

The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 6200, and the weight average molecular weight was Mw = 8100.

(Example 2)
[Polyester synthesis using tetrahydro-4- (2-propenyl) -2H-pyran-2-one and L-lactide]
Tetrahydro-4- (2-propenyl) -2H-pyran-2-one represented by the chemical formula (26) 0.28 g (2.0 mmol), L-lactide 1.44 g (10.0 mmol), 0.01 M octyl 4.8 ml of tin solution of tin oxide (tin ethyl 2-ethylhexanoate) and 4.8 ml of 0.01M p-tert-butylbenzyl alcohol toluene solution were placed in a polymer ampoule and dried under reduced pressure for 1 hour. Then, it was sealed under reduced pressure and heated to 150 ° C. to perform ring-opening polymerization. The reaction was terminated after 12 hours and cooled. The obtained polymer was dissolved in chloroform and reprecipitated in 10 times the amount of chloroform required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 1.19 g of polymer. As a result of conducting NMR analysis under the same conditions as in Example 1 to specify the structure of the obtained polymer, it is a polyhydroxyalkanoate copolymer containing a unit represented by the following chemical formula (28) as a monomer unit. It was confirmed. Moreover, it was confirmed that the ratio of the monomer unit is A unit 7 mol% and B unit 93 mol%.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 21,500, and the weight average molecular weight was Mw = 29900.

(Example 3)
[Polyester synthesis using tetrahydro-4- (2-propenyl) -2H-pyran-2-one and L-lactide]
Tetrahydro-4- (2-propenyl) -2H-pyran-2-one represented by the chemical formula (26) 1.40 g (10.0 mmol), L-lactide 7.21 g (50.0 mmol), 0.1 M octyl Tin solution of tin oxide (tin ethyl 2-ethylhexanoate) 2.4 ml, 0.1 M p-tert-butylbenzyl alcohol toluene solution 2.4 ml was charged into a polymerization ampule, dried under reduced pressure for 1 hour, and purged with nitrogen Then, it was sealed under reduced pressure and heated to 150 ° C. to perform ring-opening polymerization. The reaction was terminated after 12 hours and cooled. The obtained polymer was dissolved in chloroform and reprecipitated in 10 times the amount of chloroform required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 6.21 g of polymer. As a result of conducting NMR analysis under the same conditions as in Example 1 to specify the structure of the obtained polymer, it is a polyhydroxyalkanoate copolymer containing a unit represented by the following chemical formula (29) as a monomer unit. It was confirmed. Moreover, it was confirmed that the ratio of the monomer unit is 8 mol% A unit and 92 mol% B unit.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight Mn was 23200, and the weight average molecular weight Mw was 32200.

Example 4
[Polyester synthesis using tetrahydro-4- (2-propenyl) -2H-pyran-2-one and mandelide (3,6-diphenyl-1,4-dioxane-2,5-dione)]
Tetrahydro-4- (2-propenyl) -2H-pyran-2-one represented by the chemical formula (26) 0.28 g (2.0 mmol), mandelide 2.68 g (10.0 mmol), 0.01 M tin octylate 4.8 ml of a toluene solution of tin 2-ethylhexanoate and 4.8 ml of a 0.01 M solution of p-tert-butylbenzyl alcohol in toluene were placed in a polymerization ampule and dried under reduced pressure for 1 hour, followed by nitrogen substitution. Thereafter, it was sealed under reduced pressure and heated to 150 ° C. to perform ring-opening polymerization. The reaction was terminated after 12 hours and cooled. The obtained polymer was dissolved in chloroform and reprecipitated in 10 times the amount of chloroform required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 1.79 g of polymer.

  As a result of conducting NMR analysis under the same conditions as in Example 1 to specify the structure of the obtained polymer, it is a polyhydroxyalkanoate copolymer containing a unit represented by the following chemical formula (30) as a monomer unit. It was confirmed. Moreover, it was confirmed that the ratio of the monomer unit is 10 mol% of A unit and 90 mol% of B unit.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 18700, and the weight average molecular weight was Mw = 28800.

(Example 5)
[Polyester synthesis using tetrahydro-4- (3-butenyl) -2H-pyran-2-one and δ-valerolactone represented by chemical formula (31)]

  Tetrahydro-4- (3-butenyl) -2H-pyran-2-one represented by the chemical formula (31) 0.28 g (2.0 mmol), δ-valerolactone 1.00 g (10.0 mmol), 0 4.8 ml of 0.01M tin octylate (tin-ethylhexanoate) in toluene and 4.8 ml of 0.01M p-tert-butylbenzyl alcohol in toluene were placed in a polymerization ampule and dried under reduced pressure for 1 hour. After carrying out nitrogen substitution, it was sealed under reduced pressure and heated to 150 ° C. to perform ring-opening polymerization. The reaction was terminated after 12 hours and cooled. The obtained polymer was dissolved in chloroform and reprecipitated in 10 times the amount of chloroform required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 0.89 g of polymer.

  As a result of conducting NMR analysis under the same conditions as in Example 1 to specify the structure of the obtained polymer, it is a polyhydroxyalkanoate copolymer containing a unit represented by the following chemical formula (32) as a monomer unit. It was confirmed. Moreover, it was confirmed that the ratio of the monomer unit is 14 mol% of A unit and 86 mol% of B unit.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight Mn = 21000 and the weight average molecular weight Mw = 29000.

(Example 6)
[Polyester synthesis using 5- (2-propenyl) -2-oxepanone represented by chemical formula (33) and ε-caprolactone]

  5- (2-propenyl) -2-oxepanone represented by the chemical formula (33) 0.34 g (2.0 mmol), ε-caprolactone 1.14 g (10.0 mmol), 0.01 M tin octylate (2-ethyl) 4.8 ml of tin hexanoate solution in toluene and 4.8 ml of 0.01M p-tert-butylbenzyl alcohol in toluene were charged into the polymerization ampule, dried under reduced pressure for 1 hour, and purged with nitrogen, then under reduced pressure And heated to 150 ° C. to perform ring-opening polymerization. The reaction was terminated after 12 hours and cooled. The obtained polymer was dissolved in chloroform and reprecipitated in 10 times the amount of chloroform required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 0.96 g of polymer.

  As a result of conducting NMR analysis under the same conditions as in Example 1 in order to specify the structure of the obtained polymer, it is a polyhydroxyalkanoate copolymer containing a unit represented by the following chemical formula (34) as a monomer unit. It was confirmed. Moreover, it was confirmed that the ratio of the monomer unit is 13 mol% of A unit and 87 mol% of B unit.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight Mn = 2225 and the weight average molecular weight Mw = 32000.

(Example 7)
[Polyester synthesis using 7-oxo-3-oxepanecarboxylic acid phenylmethyl ester represented by chemical formula (35) and ε-caprolactone]

  7-oxo-3-oxepanecarboxylic acid phenylmethyl ester represented by the chemical formula (35) 0.50 g (2.0 mmol), ε-caprolactone 1.14 g (10.0 mmol), 0.01 M tin octylate (2 -Tin ethylhexanoate) 4.8 ml, 0.01 M p-tert-butylbenzyl alcohol toluene solution 4.8 ml was charged into a polymerization ampule, dried under reduced pressure for 1 hour, and purged with nitrogen. Sealed under reduced pressure and heated to 150 ° C. to perform ring-opening polymerization. The reaction was terminated after 12 hours and cooled. The obtained polymer was dissolved in chloroform and reprecipitated in 10 times the amount of chloroform required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 1.23 g of polymer.

  As a result of performing NMR analysis under the same conditions as in Example 1 in order to specify the structure of the obtained polymer, it is a polyhydroxyalkanoate copolymer containing a unit represented by the following chemical formula (36) as a monomer unit. It was confirmed. Moreover, it was confirmed that the ratio of the monomer unit is 14 mol% of A unit and 86 mol% of B unit.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 12000 and the weight average molecular weight was Mw = 16000.

  1.00 g of the polyhydroxyalkanoate copolymer represented by the chemical formula (36) obtained here was dissolved in 100 ml of a mixed solvent of dioxane-ethanol (75:25), and 0.22 g of 5% palladium / carbon catalyst was added thereto. The reaction system was filled with hydrogen and stirred at room temperature for 1 day. After the reaction, in order to remove the catalyst, the reaction solution was collected by filtration through a 0.25 μm membrane filter. The solution was concentrated, dissolved in chloroform, and reprecipitated in 10 times the amount of methanol. The obtained polymer was collected and dried under reduced pressure to obtain 0.75 g of polymer.

  As a result of conducting NMR analysis under the same conditions as in Example 1 to identify the structure of the obtained polymer, it is a polyhydroxyalkanoate copolymer containing a unit represented by the following chemical formula (37) as a monomer unit. It was confirmed. Moreover, it was confirmed that the ratio of the monomer unit is C unit 14 mol% and D unit 86 mol%.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 10600, and the weight average molecular weight was Mw = 14700.

(Example 8)
[Polyester synthesis using 7-oxo-4-oxepanecarboxylic acid phenylmethyl ester represented by chemical formula (38) and L-lactide]

  7-oxo-4-oxepanecarboxylic acid phenylmethyl ester represented by the chemical formula (38) 2.48 g (10.0 mmol), L-lactide 7.21 g (50.0 mmol), 0.1 M tin octylate (2 -Tin ethylhexanoate) 2.4 ml, 0.1 M p-tert-butylbenzyl alcohol in toluene 2.4 ml was charged into a polymerization ampule, dried under reduced pressure for 1 hour, and purged with nitrogen. Sealed under reduced pressure and heated to 150 ° C. to perform ring-opening polymerization. The reaction was terminated after 12 hours and cooled. The obtained polymer was dissolved in chloroform and reprecipitated in 10 times the amount of chloroform required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 7.08 g of polymer.

  As a result of conducting NMR analysis under the same conditions as in Example 1 to specify the structure of the obtained polymer, it is a polyhydroxyalkanoate copolymer containing a unit represented by the following chemical formula (39) as a monomer unit. It was confirmed. Moreover, it was confirmed that the ratio of the monomer unit is 8 mol% A unit and 92 mol% B unit.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 10300, and the weight average molecular weight was Mw = 14800.

  5.00 g of the polyhydroxyalkanoate copolymer represented by the chemical formula (39) obtained here was dissolved in 500 ml of a mixed solvent of dioxane-ethanol (75:25), and 1.10 g of 5% palladium / carbon catalyst was dissolved therein. The reaction system was filled with hydrogen and stirred at room temperature for 1 day. After the reaction, in order to remove the catalyst, the reaction solution was collected by filtration through a 0.25 μm membrane filter. The solution was concentrated, dissolved in chloroform, and reprecipitated in 10 times the amount of methanol. The polymer obtained was collected and dried under reduced pressure to obtain 3.70 g of polymer.

  As a result of conducting NMR analysis under the same conditions as in Example 1 in order to specify the structure of the obtained polymer, it is a polyhydroxyalkanoate copolymer containing a unit represented by the following chemical formula (40) as a monomer unit. It was confirmed. Moreover, it was confirmed that the ratio of the monomer unit is C unit 8 mol% and D unit 92 mol%.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 9500, and the weight average molecular weight was Mw = 1900.

Example 9
[Polyester Synthesis Using Tetrahydro-6-oxo-2H-pyran-3-carboxylic acid phenylmethyl ester represented by Chemical Formula (41) and Mandelide]

Tetrahydro-6-oxo-2H-pyran-3-carboxylic acid phenylmethyl ester represented by chemical formula (41) 0.47 g (2.0 mmol), mandelide 2.68 g (10.0 mmol), 0.01 M tin octylate 4.8 ml of a toluene solution of tin 2-ethylhexanoate and 4.8 ml of a 0.01 M solution of p-tert-butylbenzyl alcohol in toluene were placed in a polymerization ampule and dried under reduced pressure for 1 hour, followed by nitrogen substitution. Thereafter, it was sealed under reduced pressure and heated to 150 ° C. to perform ring-opening polymerization. The reaction was terminated after 12 hours and cooled. The obtained polymer was dissolved in chloroform and reprecipitated in 10 times the amount of chloroform required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 2.06 g of polymer.
As a result of conducting NMR analysis under the same conditions as in Example 1 to specify the structure of the obtained polymer, it is a polyhydroxyalkanoate copolymer containing a unit represented by the following chemical formula (42) as a monomer unit. It was confirmed. Moreover, it was confirmed that the ratio of the monomer unit is A unit 7 mol% and B unit 93 mol%.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 12000 and the weight average molecular weight was Mw = 16000.

  1.00 g of the polyhydroxyalkanoate copolymer represented by the chemical formula (42) obtained here was dissolved in 100 ml of a mixed solvent of dioxane-ethanol (75:25), and 0.22 g of 5% palladium / carbon catalyst was added thereto. The reaction system was filled with hydrogen and stirred at room temperature for 1 day. After the reaction, in order to remove the catalyst, the reaction solution was collected by filtration through a 0.25 μm membrane filter. The solution was concentrated, dissolved in chloroform, and reprecipitated in 10 times the amount of methanol. The obtained polymer was collected and dried under reduced pressure to obtain 0.73 g of polymer.

  As a result of conducting NMR analysis under the same conditions as in Example 1 to identify the structure of the obtained polymer, it is a polyhydroxyalkanoate copolymer containing a unit represented by the following chemical formula (43) as a monomer unit. It was confirmed. Moreover, it was confirmed that the ratio of the monomer unit is C unit 7 mol% and D unit 93 mol%.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 8700, and the weight average molecular weight was Mw = 1900.

(Example 10)
Oxidation reaction of polyhydroxyalkanoate comprising unit represented by chemical formula (27) synthesized in Example 1

  0.50 g of a polyhydroxyalkanoate composed of the unit represented by the chemical formula (27) obtained in Example 1 was added to an eggplant flask, and dissolved by adding 30 ml of acetone. This was placed in an ice bath, 5 ml of acetic acid and 2.83 g of 18-crown-6-ether were added and stirred. Next, 2.25 g of potassium permanganate was slowly added in an ice bath, stirred for 2 hours in an ice bath, and further stirred for 18 hours at room temperature. After completion of the reaction, 60 ml of ethyl acetate was added and 45 ml of water was further added. Sodium bisulfite was then added until the peracid was removed. Thereafter, the liquid property was adjusted to pH = 1 with 1.0 N hydrochloric acid. The organic layer was extracted and washed 3 times with 1.0N hydrochloric acid. After recovering the organic layer, the solvent was distilled off to recover the crude polymer. Next, it was washed with 50 ml of water and 50 ml of methanol, and further washed with 50 ml of water three times, and then the polymer was recovered. Next, it was dissolved in 3 ml of THF, and reprecipitated in 50 times the amount of THF required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 0.42 g of polymer.

  As a result of conducting NMR analysis under the same conditions as in Example 1 to specify the structure of the obtained polymer, it was confirmed that the monomer unit was a polyhydroxyalkanoate containing a unit represented by the following chemical formula (44). It was done.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 4700, and the weight average molecular weight was Mw = 6200.

(Example 11)
Oxidation reaction of polyhydroxyalkanoate comprising unit represented by chemical formula (28) synthesized in Example 2

  0.50 g of a polyhydroxyalkanoate copolymer (A: 7 mol%, B: 93 mol%) composed of the unit represented by the chemical formula (28) obtained in Example 2 was added to an eggplant flask, and 30 ml of acetone was added. Dissolved. This was placed in an ice bath, 5 ml of acetic acid and 0.36 g of 18-crown-6-ether were added and stirred. Next, 0.28 g of potassium permanganate was slowly added in an ice bath, stirred for 2 hours in an ice bath, and further stirred at room temperature for 18 hours. After completion of the reaction, 60 ml of ethyl acetate was added and 45 ml of water was further added. Sodium bisulfite was then added until the peracid was removed. Thereafter, the liquid property was adjusted to pH = 1 with 1.0 N hydrochloric acid. The organic layer was extracted and washed 3 times with 1.0N hydrochloric acid. After recovering the organic layer, the solvent was distilled off to recover the crude polymer. Next, it was washed with 50 ml of water and 50 ml of methanol, and further washed with 50 ml of water three times, and then the polymer was recovered. Next, it was dissolved in 3 ml of THF, then dissolved in THF, and reprecipitated in 50 times the amount of THF required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 0.43 g of polymer.

  As a result of conducting NMR analysis under the same conditions as in Example 1 to identify the structure of the obtained polymer, it was confirmed that the monomer unit was a polyhydroxyalkanoate containing a unit represented by the following chemical formula (45). It was done.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 17400, and the weight average molecular weight was Mw = 23800.

  Furthermore, in order to calculate the unit of the obtained polyhydroxyalkanoate, it calculated by methyl-esterifying the carboxyl group in the side chain terminal of polyhydroxyalkanoate using trimethylsilyldiazomethane.

  30 mg of the target polyhydroxyalkanoate was added to a 100 ml eggplant flask, and dissolved by adding 2.1 ml of chloroform and 0.7 ml of methanol. To this was added 0.5 ml of a 2 mol / L trimethylsilyldiazomethane-hexane solution, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the solvent was distilled off and the polymer was recovered. The polymer was recovered after washing with 50 ml of methanol. 30 mg of polyhydroxyalkanoate was obtained by drying under reduced pressure.

  NMR analysis was performed using the same method as in Example 1. As a result, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (45) was a copolymer of 7 mol% for the C unit and 93 mol% for the D unit.

(Example 12)
Oxidation reaction of polyhydroxyalkanoate composed of unit represented by chemical formula (29) synthesized in Example 3

  5.00 g of a polyhydroxyalkanoate copolymer (A: 8 mol%, B: 92 mol%) comprising the unit represented by the chemical formula (29) obtained in Example 3 was added to an eggplant flask, and 300 ml of acetone was added. Dissolved. This was placed in an ice bath, 50 ml of acetic acid and 4.09 g of 18-crown-6-ether were added and stirred. Next, 3.26 g of potassium permanganate was slowly added in an ice bath, stirred for 2 hours in an ice bath, and further stirred for 18 hours at room temperature. After completion of the reaction, 600 ml of ethyl acetate was added, and 450 ml of water was further added. Sodium bisulfite was then added until the peracid was removed. Thereafter, the liquid property was adjusted to pH = 1 with 1.0 N hydrochloric acid. The organic layer was extracted and washed 3 times with 1.0N hydrochloric acid. After recovering the organic layer, the solvent was distilled off to recover the crude polymer. Next, after washing with 500 ml of water and 500 ml of methanol, and further washing with 500 ml of water three times, the polymer was recovered. Next, it was dissolved in 30 ml of THF and reprecipitated in 50 times the amount of THF required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 4.38 g of polymer.

  As a result of conducting NMR analysis under the same conditions as in Example 1 to specify the structure of the obtained polymer, it was confirmed that the monomer unit was a polyhydroxyalkanoate containing a unit represented by the following chemical formula (46). It was done.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 19800, and the weight average molecular weight was Mw = 27900.

  Furthermore, in order to calculate the unit of the obtained polyhydroxyalkanoate, it calculated by methyl-esterifying the carboxyl group in the side chain terminal of polyhydroxyalkanoate using trimethylsilyldiazomethane.

  30 mg of the target polyhydroxyalkanoate was added to a 100 ml eggplant flask, and dissolved by adding 2.1 ml of chloroform and 0.7 ml of methanol. To this was added 0.5 ml of a 2 mol / L trimethylsilyldiazomethane-hexane solution, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the solvent was distilled off and the polymer was recovered. The polymer was recovered after washing with 50 ml of methanol. 30 mg of polyhydroxyalkanoate was obtained by drying under reduced pressure.

  NMR analysis was performed using the same method as in Example 1. As a result, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (46) was a copolymer of 8 mol% for the C unit and 92 mol% for the D unit.

(Example 13)
Oxidation reaction of polyhydroxyalkanoate comprising unit represented by chemical formula (30) synthesized in Example 4

  0.50 g of a polyhydroxyalkanoate copolymer (A: 10 mol%, B: 90 mol%) composed of the unit represented by the chemical formula (30) obtained in Example 4 was added to an eggplant flask, and 30 ml of acetone was added. Dissolved. This was placed in an ice bath, 5 ml of acetic acid and 0.29 g of 18-crown-6-ether were added and stirred. Next, 0.23 g of potassium permanganate was slowly added in an ice bath, stirred for 2 hours in an ice bath, and further stirred for 18 hours at room temperature. After completion of the reaction, 60 ml of ethyl acetate was added and 45 ml of water was further added. Sodium bisulfite was then added until the peracid was removed. Thereafter, the liquid property was adjusted to pH = 1 with 1.0 N hydrochloric acid. The organic layer was extracted and washed 3 times with 1.0N hydrochloric acid. After recovering the organic layer, the solvent was distilled off to recover the crude polymer. Next, it was washed with 50 ml of water and 50 ml of methanol, and further washed with 50 ml of water three times, and then the polymer was recovered. Next, it was dissolved in 3 ml of THF, and reprecipitated in 50 times the amount of THF required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 0.41 g of polymer.

  As a result of conducting NMR analysis under the same conditions as in Example 1 to specify the structure of the obtained polymer, it was confirmed that the monomer unit was a polyhydroxyalkanoate containing a unit represented by the following chemical formula (47). It was done.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 15500, and the weight average molecular weight was Mw = 20300.

  Furthermore, in order to calculate the unit of the obtained polyhydroxyalkanoate, it calculated by methyl-esterifying the carboxyl group in the side chain terminal of polyhydroxyalkanoate using trimethylsilyldiazomethane.

  30 mg of the target polyhydroxyalkanoate was added to a 100 ml eggplant flask, and dissolved by adding 2.1 ml of chloroform and 0.7 ml of methanol. To this was added 0.5 ml of a 2 mol / L trimethylsilyldiazomethane-hexane solution, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the solvent was distilled off and the polymer was recovered. The polymer was recovered after washing with 50 ml of methanol. By drying under reduced pressure, 28 mg of polyhydroxyalkanoate was obtained.

  NMR analysis was performed using the same method as in Example 1. As a result, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (47) was a copolymer of 10 mol% for the C unit and 90 mol% for the D unit.

(Example 14)
Oxidation reaction of polyhydroxyalkanoate comprising unit represented by chemical formula (32) synthesized in Example 5

  0.50 g of a polyhydroxyalkanoate copolymer (A: 14 mol%, B: 86 mol%) composed of the unit represented by the chemical formula (32) obtained in Example 5 was added to an eggplant flask, and 30 ml of acetone was added. Dissolved. This was placed in an ice bath, 5 ml of acetic acid and 0.52 g of 18-crown-6-ether were added and stirred. Next, 0.42 g of potassium permanganate was slowly added in an ice bath, stirred for 2 hours in an ice bath, and further stirred for 18 hours at room temperature. After completion of the reaction, 60 ml of ethyl acetate was added and 45 ml of water was further added. Sodium bisulfite was then added until the peracid was removed. Thereafter, the liquid property was adjusted to pH = 1 with 1.0 N hydrochloric acid. The organic layer was extracted and washed 3 times with 1.0N hydrochloric acid. After recovering the organic layer, the solvent was distilled off to recover the crude polymer. Next, it was washed with 50 ml of water and 50 ml of methanol, and further washed with 50 ml of water three times, and then the polymer was recovered. Next, it was dissolved in 3 ml of THF, and reprecipitated in 50 times the amount of THF required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 0.43 g of polymer.

  As a result of conducting NMR analysis under the same conditions as in Example 1 to identify the structure of the obtained polymer, it was confirmed that the monomer unit was a polyhydroxyalkanoate containing a unit represented by the following chemical formula (48). It was done.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 17900 and the weight average molecular weight was Mw = 24500.

  Furthermore, in order to calculate the unit of the obtained polyhydroxyalkanoate, it calculated by methyl-esterifying the carboxyl group in the side chain terminal of polyhydroxyalkanoate using trimethylsilyldiazomethane.

  30 mg of the target polyhydroxyalkanoate was added to a 100 ml eggplant flask, and dissolved by adding 2.1 ml of chloroform and 0.7 ml of methanol. To this was added 0.5 ml of a 2 mol / L trimethylsilyldiazomethane-hexane solution, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the solvent was distilled off and the polymer was recovered. The polymer was recovered after washing with 50 ml of methanol. 29 mg of polyhydroxyalkanoate was obtained by drying under reduced pressure.

  NMR analysis was performed using the same method as in Example 1. As a result, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (48) was a copolymer of 13 mol% for the C unit and 87 mol% for the D unit.

(Example 15)
Oxidation reaction of polyhydroxyalkanoate composed of unit represented by chemical formula (34) synthesized in Example 6

  0.50 g of a polyhydroxyalkanoate copolymer (A: 13 mol%, B: 87 mol%) comprising the unit represented by the chemical formula (34) obtained in Example 6 was added to an eggplant flask, and 30 ml of acetone was added. Dissolved. This was placed in an ice bath, 5 ml of acetic acid and 0.43 g of 18-crown-6-ether were added and stirred. Next, 0.34 g of potassium permanganate was slowly added in an ice bath, stirred for 2 hours in an ice bath, and further stirred for 18 hours at room temperature. After completion of the reaction, 60 ml of ethyl acetate was added and 45 ml of water was further added. Sodium bisulfite was then added until the peracid was removed. Thereafter, the liquid property was adjusted to pH = 1 with 1.0 N hydrochloric acid. The organic layer was extracted and washed 3 times with 1.0N hydrochloric acid. After recovering the organic layer, the solvent was distilled off to recover the crude polymer. Next, it was washed with 50 ml of water and 50 ml of methanol, and further washed with 50 ml of water three times, and then the polymer was recovered. Next, it was dissolved in 3 ml of THF, and reprecipitated in 50 times the amount of THF required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 0.44 g of polymer.

  As a result of conducting NMR analysis under the same conditions as in Example 1 to specify the structure of the obtained polymer, it was confirmed that the monomer unit was a polyhydroxyalkanoate containing a unit represented by the following chemical formula (49). It was done.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 18900, and the weight average molecular weight was Mw = 27600.

  Furthermore, in order to calculate the unit of the obtained polyhydroxyalkanoate, it calculated by methyl-esterifying the carboxyl group in the side chain terminal of polyhydroxyalkanoate using trimethylsilyldiazomethane.

  30 mg of the target polyhydroxyalkanoate was added to a 100 ml eggplant flask, and dissolved by adding 2.1 ml of chloroform and 0.7 ml of methanol. To this was added 0.5 ml of a 2 mol / L trimethylsilyldiazomethane-hexane solution, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the solvent was distilled off and the polymer was recovered. The polymer was recovered after washing with 50 ml of methanol. By drying under reduced pressure, 28 mg of polyhydroxyalkanoate was obtained.

  NMR analysis was performed using the same method as in Example 1. As a result, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (49) was a copolymer of 12 mol% for the C unit and 88 mol% for the D unit.

(Example 16)
Condensation reaction of polyhydroxyalkanoate comprising unit represented by chemical formula (46) synthesized in Example 12 and 2-aminobenzenesulfonic acid

  In a nitrogen atmosphere, 0.40 g of a polyhydroxyalkanoate copolymer (C: 8 mol%, D: 92 mol%) comprising the unit represented by the chemical formula (46) obtained in Example 12 and 2-aminobenzenesulfonic acid 0.35 g was placed in a 100 ml three-necked flask, 15.0 ml of pyridine was added and stirred, 1.06 ml of triphenyl phosphite was added, and the mixture was heated at 120 ° C. for 6 hours. After completion of the reaction, it was recovered by reprecipitation in 150 ml of ethanol. The obtained polymer was washed with 1N hydrochloric acid for 1 day, then washed by stirring in water for 1 day, and dried under reduced pressure to obtain 0.34 g of polymer.

The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature), Fourier transform-infrared absorption Analysis was performed by (FT-IR) spectrum (Nicolet AVATAR360FT-IR). As a result of IR measurement, the peak at 1695 cm ⁻¹ derived from the carboxylic acid decreased, and a new peak derived from the amide group was observed at 1658 cm ⁻¹ . ^From the result of ¹ H-NMR, since the peak derived from the aromatic ring having a 2-aminobenzenesulfonic acid structure is shifted, the obtained polymer has a unit represented by the following chemical formula (50) as a monomer unit. It was confirmed to be a polyhydroxyalkanoate containing.

  Further, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (50) was a copolymer of 8 mol% for the E unit and 92 mol% for the F unit.

The average molecular weight of the obtained polymer was gel permeation chromatography (GPC; Tosoh HLC-8120, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene. (Conversion). As a result, the number average molecular weight M _n = 16700 and the weight average molecular weight M _w = 24700.

(Example 17)
Condensation reaction of polyhydroxyalkanoate comprising unit represented by chemical formula (46) synthesized in Example 12 and 4-aminobenzenesulfonic acid

  0.40 g of 4-hydroxybenzenesulfonic acid, a polyhydroxyalkanoate copolymer (C: 8 mol%, D: 92 mol%) composed of the unit represented by the chemical formula (46) obtained in Example 12 under a nitrogen atmosphere 0.35 g was placed in a 100 ml three-necked flask, 15.0 ml of pyridine was added and stirred, 1.06 ml of triphenyl phosphite was added, and the mixture was heated at 120 ° C. for 6 hours. After completion of the reaction, it was recovered by reprecipitation in 150 ml of ethanol. The obtained polymer was washed with 1N hydrochloric acid for 1 day, then washed by stirring in water for 1 day, and dried under reduced pressure to obtain 0.32 g of polymer.

The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature), Fourier transform-infrared absorption Analysis was performed by (FT-IR) spectrum (Nicolet AVATAR360FT-IR). As a result of IR measurement, the peak at 1695 cm ⁻¹ derived from the carboxylic acid decreased, and a new peak derived from the amide group was observed at 1658 cm ⁻¹ .
^From the result of ¹ H-NMR, since the peak derived from the aromatic ring having a 4-aminobenzenesulfonic acid structure is shifted, the obtained polymer has a unit represented by the following chemical formula (51) as a monomer unit. It was confirmed to be a polyhydroxyalkanoate containing.

  Further, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (51) was a copolymer of 8 mol% for the E unit and 92 mol% for the F unit.

The average molecular weight of the obtained polymer was gel permeation chromatography (GPC; Tosoh HLC-8120, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene. (Conversion). As a result, the number average molecular weight M _n = 16100 and the weight average molecular weight M _w = 24300.

(Example 18)
Condensation reaction of polyhydroxyalkanoate comprising unit represented by chemical formula (46) synthesized in Example 12 and p-toluidine-2-sulfonic acid

  Under a nitrogen atmosphere, 0.40 g of a polyhydroxyalkanoate copolymer (C: 8 mol%, D: 92 mol%) comprising the unit represented by the chemical formula (46) obtained in Example 12 was added to p-toluidine-2- 0.38 g of sulfonic acid was placed in a 100 ml three-necked flask, 15.0 ml of pyridine was added and stirred, 1.06 ml of triphenyl phosphite was added, and the mixture was heated at 120 ° C. for 6 hours. After completion of the reaction, it was recovered by reprecipitation in 150 ml of ethanol. The obtained polymer was washed with 1N hydrochloric acid for 1 day, then washed by stirring in water for 1 day, and dried under reduced pressure to obtain 0.35 g of polymer.

The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature), Fourier transform-infrared absorption Analysis was performed by (FT-IR) spectrum (Nicolet AVATAR360FT-IR). As a result of IR measurement, the peak at 1695 cm ⁻¹ derived from the carboxylic acid decreased, and a new peak derived from the amide group was observed at 1658 cm ⁻¹ .
^From the result of ¹ H-NMR, since the peak derived from the aromatic ring having a p-toluidine-2-sulfonic acid structure is shifted, the obtained polymer is represented by the following chemical formula (52) as a monomer unit. It was confirmed to be a polyhydroxyalkanoate containing unit.

  Further, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (52) was a copolymer of 8 mol% for the E unit and 92 mol% for the F unit.

The average molecular weight of the obtained polymer was gel permeation chromatography (GPC; Tosoh HLC-8120, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene. (Conversion). As a result, the number average molecular weight M _n = 15700 and the weight average molecular weight M _w = 24600.

(Example 19)
Condensation reaction of polyhydroxyalkanoate composed of the unit represented by chemical formula (46) synthesized in Example 12 and 2-aminobenzenesulfonic acid phenyl ester

  In a nitrogen atmosphere, 0.40 g of a polyhydroxyalkanoate copolymer (C: 8 mol%, D: 92 mol%) comprising the unit represented by the chemical formula (46) obtained in Example 12 and 2-aminobenzenesulfonic acid 0.51 g of phenyl ester was put in a 100 ml three-necked flask, 15.0 ml of pyridine was added and stirred, 1.06 ml of triphenyl phosphite was added, and the mixture was heated at 120 ° C. for 6 hours. After completion of the reaction, it was recovered by reprecipitation in 150 ml of ethanol. The obtained polymer was washed with 1N hydrochloric acid for 1 day, then washed by stirring in water for 1 day, and dried under reduced pressure to obtain 0.38 g of polymer.

The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature), Fourier transform-infrared absorption Analysis was performed by (FT-IR) spectrum (Nicolet AVATAR360FT-IR). As a result of IR measurement, the peak at 1695 cm ⁻¹ derived from the carboxylic acid decreased, and a new peak derived from the amide group was observed at 1658 cm ⁻¹ .

^From the result of ¹ H-NMR, since the peak derived from the aromatic ring of 2-aminobenzenesulfonic acid phenyl ester structure is shifted, the obtained polymer is represented by the following chemical formula (53) as a monomer unit. It was confirmed to be a polyhydroxyalkanoate containing unit.

Further, it was confirmed that the units of the polyhydroxyalkanoate represented by the chemical formula (53) were 8 mol% of the E unit and 92 mol% of the F unit.

The average molecular weight of the obtained polymer was gel permeation chromatography (GPC; Tosoh HLC-8120, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene. (Conversion). As a result, the number average molecular weight M _n = 17100 and the weight average molecular weight M _w = 24600.

(Example 20)
Condensation reaction between a polyhydroxyalkanoate composed of the unit represented by the chemical formula (46) synthesized in Example 12 and 2-amino-1-naphthalenesulfonic acid

  Under a nitrogen atmosphere, 0.40 g of a polyhydroxyalkanoate copolymer (C: 8 mol%, D: 92 mol%) composed of the unit represented by the chemical formula (46) obtained in Example 12 was obtained, and 2-amino-1- After putting 0.45 g of naphthalenesulfonic acid into a 100 ml three-necked flask and adding 15.0 ml of pyridine and stirring, 1.06 ml of triphenyl phosphite was added and heated at 120 ° C. for 6 hours. After completion of the reaction, it was recovered by reprecipitation in 150 ml of ethanol. The obtained polymer was washed with 1N hydrochloric acid for 1 day, then washed by stirring in water for 1 day, and dried under reduced pressure to obtain 0.34 g of polymer.

The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature), Fourier transform-infrared absorption Analysis was performed by (FT-IR) spectrum (Nicolet AVATAR360FT-IR). As a result of IR measurement, the peak at 1695 cm ⁻¹ derived from the carboxylic acid decreased, and a new peak derived from the amide group was observed at 1658 cm ⁻¹ .

^From the result of ¹ H-NMR, since the peak derived from the aromatic ring having the 2-amino-1-naphthalenesulfonic acid structure is shifted, the obtained polymer is represented by the following chemical formula (54) as a monomer unit. It was confirmed that this was a polyhydroxyalkanoate containing unit.

  In addition, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (54) was a copolymer of 8 mol% for the E unit and 92 mol% for the F unit.

The average molecular weight of the obtained polymer was gel permeation chromatography (GPC; Tosoh HLC-8120, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene. (Conversion). As a result, the number average molecular weight M _n = 16900 and the weight average molecular weight M _w = 25700.

(Example 21)
Condensation reaction of polyhydroxyalkanoate composed of the unit represented by chemical formula (46) synthesized in Example 12 and 2-amino-2-methylpropanesulfonic acid

  Under a nitrogen atmosphere, 0.40 g of a polyhydroxyalkanoate copolymer (C: 8 mol%, D: 92 mol%) composed of the unit represented by the chemical formula (46) obtained in Example 12 was obtained. 0.31 g of methylpropanesulfonic acid was placed in a 100 ml three-necked flask, 15.0 ml of pyridine was added and stirred, 1.06 ml of triphenyl phosphite was added, and the mixture was heated at 120 ° C. for 6 hours. After completion of the reaction, it was recovered by reprecipitation in 150 ml of ethanol. The obtained polymer was washed with 1N hydrochloric acid for 1 day, then washed by stirring in water for 1 day, and dried under reduced pressure to obtain 0.31 g of polymer.

The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature), Fourier transform-infrared absorption Analysis was performed by (FT-IR) spectrum (Nicolet AVATAR360FT-IR). As a result of IR measurement, the peak at 1695 cm ⁻¹ derived from carboxylic acid decreased, and a new peak derived from the amide group was observed at 1668 cm ⁻¹ .

^From the result of ¹ H-NMR, since the peak derived from methylene having a 2-amino-2-methylpropanesulfonic acid structure is shifted, the obtained polymer is represented by the following chemical formula (55) as a monomer unit. It was confirmed that this was a polyhydroxyalkanoate containing unit.

  Further, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (55) was a copolymer of 8 mol% for the E unit and 92 mol% for the F unit.

The average molecular weight of the obtained polymer was gel permeation chromatography (GPC; Tosoh HLC-8120, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene. (Conversion). As a result, the number average molecular weight M _n = 17300 and the weight average molecular weight M _w = 24600.

(Example 22)
Condensation reaction of polyhydroxyalkanoate composed of the unit represented by chemical formula (47) synthesized in Example 13 and 3-aminobenzenesulfonic acid

  0.40 g of a polyhydroxyalkanoate copolymer (C: 10 mol%, D: 90 mol%) composed of the unit represented by the chemical formula (47) obtained in Example 13 in a nitrogen atmosphere, 3-aminobenzenesulfonic acid 0.25 g was placed in a 100 ml three-necked flask, 15.0 ml of pyridine was added and stirred, 0.76 ml of triphenyl phosphite was added, and the mixture was heated at 120 ° C. for 6 hours. After completion of the reaction, it was recovered by reprecipitation in 150 ml of ethanol. The obtained polymer was washed with 1N hydrochloric acid for 1 day, then washed by stirring in water for 1 day, and dried under reduced pressure to obtain 0.33 g of polymer.

The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature), Fourier transform-infrared absorption Analysis was performed by (FT-IR) spectrum (Nicolet AVATAR360FT-IR). As a result of IR measurement, the peak at 1695 cm ⁻¹ derived from the carboxylic acid decreased, and a new peak derived from the amide group was observed at 1658 cm ⁻¹ .

^From the result of ¹ H-NMR, since the peak derived from the aromatic ring of the 3-aminobenzenesulfonic acid structure is shifted, the obtained polymer has a unit represented by the following chemical formula (56) as a monomer unit. It was confirmed to be a polyhydroxyalkanoate containing.

In addition, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (56) was a copolymer of 10 mol% for the E unit and 90 mol% for the F unit.

The average molecular weight of the obtained polymer was gel permeation chromatography (GPC; Tosoh HLC-8120, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene. (Conversion). As a result, the number average molecular weight M _n = 13100 and the weight average molecular weight M _w = 17700.

(Example 23)
Condensation reaction of polyhydroxyalkanoate comprising unit represented by chemical formula (48) synthesized in Example 14 and 4-methoxyaniline-2-sulfonic acid

  Under a nitrogen atmosphere, 0.40 g of a polyhydroxyalkanoate copolymer (C: 13 mol%, D: 87 mol%) comprising the unit represented by the chemical formula (48) obtained in Example 14 and 4-methoxyaniline-2 -A sulfonic acid 0.48g was put into a 100 ml three necked flask, 15.0 ml of pyridine was added and stirred, then 1.24 ml of triphenyl phosphite was added, and it heated at 120 degreeC for 6 hours. After completion of the reaction, it was recovered by reprecipitation in 150 ml of ethanol. The obtained polymer was washed with 1N hydrochloric acid for 1 day, then washed by stirring in water for 1 day, and dried under reduced pressure to obtain 0.37 g of polymer.

The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature), Fourier transform-infrared absorption Analysis was performed by (FT-IR) spectrum (Nicolet AVATAR360FT-IR). As a result of IR measurement, the peak at 1695 cm ⁻¹ derived from the carboxylic acid decreased, and a new peak derived from the amide group was observed at 1658 cm ⁻¹ .

^From the result of ¹ H-NMR, since the peak derived from the aromatic ring having a 4-methoxyaniline-2-sulfonic acid structure is shifted, the obtained polymer is represented by the following chemical formula (57) as a monomer unit. It was confirmed that this was a polyhydroxyalkanoate containing unit.

  Further, it was confirmed that the unit of polyhydroxyalkanoate represented by the chemical formula (57) was a copolymer of 13 mol% for the E unit and 87 mol% for the F unit.

The average molecular weight of the obtained polymer was determined by gel permeation chromatography (GPC; Tosoh, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene conversion). evaluated. As a result, the number average molecular weight M _n = 14800 and the weight average molecular weight M _w = 20600.

(Example 24)
Condensation reaction of polyhydroxyalkanoate composed of the unit represented by the chemical formula (49) synthesized in Example 15 and taurine

  Under a nitrogen atmosphere, 0.40 g of a polyhydroxyalkanoate copolymer (C: 12 mol%, D: 88 mol%) composed of the unit represented by the chemical formula (49) obtained in Example 15 and 100 ml of taurine 0.25 g After putting in a three-necked flask and adding 15.0 ml of pyridine and stirring, 1.03 ml of triphenyl phosphite was added and heated at 120 ° C. for 6 hours. After completion of the reaction, it was recovered by reprecipitation in 150 ml of ethanol. The obtained polymer was washed with 1N hydrochloric acid for 1 day, then washed by stirring in water for 1 day, and dried under reduced pressure to obtain 0.31 g of polymer.

The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature), Fourier transform-infrared absorption Analysis was performed by (FT-IR) spectrum (Nicolet AVATAR360FT-IR). As a result of IR measurement, the peak at 1695 cm ⁻¹ derived from carboxylic acid decreased, and a new peak derived from the amide group was observed at 1668 cm ⁻¹ .

^From the result of ¹ H-NMR, since the peak derived from methylene having a taurine structure is shifted, the obtained polymer is a polyhydroxyalkanoate containing a unit represented by the following chemical formula (58) as a monomer unit. It was confirmed that there was.

  Further, it was confirmed that the units of the polyhydroxyalkanoate represented by the chemical formula (58) were 12 mol% of the E unit and 88 mol% of the F unit.

The average molecular weight of the obtained polymer was gel permeation chromatography (GPC; Tosoh HLC-8120, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene. (Conversion). As a result, the number average molecular weight M _n = 15500 and the weight average molecular weight M _w = 22200.

(Example 25)
Condensation reaction of polyhydroxyalkanoate composed of the unit represented by the chemical formula (37) synthesized in Example 7 and 2-aminobenzenesulfonic acid

  In a nitrogen atmosphere, 0.40 g of a polyhydroxyalkanoate copolymer (C: 14 mol%, D: 86 mol%) comprising the unit represented by the chemical formula (37) obtained in Example 7 and 2-aminobenzenesulfonic acid 0.40 g was placed in a 100 ml three-necked flask, 15.0 ml of pyridine was added and stirred, 1.21 ml of triphenyl phosphite was added, and the mixture was heated at 120 ° C. for 6 hours. After completion of the reaction, it was recovered by reprecipitation in 150 ml of ethanol. The obtained polymer was washed with 1N hydrochloric acid for 1 day, then washed by stirring in water for 1 day, and dried under reduced pressure to obtain 0.36 g of polymer.

The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature), Fourier transform-infrared absorption Analysis was performed by (FT-IR) spectrum (Nicolet AVATAR360FT-IR). As a result of IR measurement, the peak at 1695 cm ⁻¹ derived from the carboxylic acid decreased, and a new peak derived from the amide group was observed at 1658 cm ⁻¹ .

^From the result of ¹ H-NMR, since the peak derived from the aromatic ring having a 2-aminobenzenesulfonic acid structure is shifted, the obtained polymer has a unit represented by the following chemical formula (59) as a monomer unit. It was confirmed to be a polyhydroxyalkanoate containing.

  Further, it was confirmed that the units of the polyhydroxyalkanoate represented by the chemical formula (59) were 14 mol% of the E unit and 86 mol% of the F unit.

The average molecular weight of the obtained polymer was gel permeation chromatography (GPC; Tosoh HLC-8120, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene. (Conversion). As a result, the number average molecular weight M _n = 9400 and the weight average molecular weight M _w = 13400.

(Example 26)
Condensation reaction of polyhydroxyalkanoate composed of the unit represented by chemical formula (40) synthesized in Example 8 and 2-amino-2-methylpropanesulfonic acid

  0.40 g of polyhydroxyalkanoate copolymer (C: 8 mol%, D: 92 mol%) composed of the unit represented by the chemical formula (40) obtained in Example 8 under a nitrogen atmosphere, 2-amino-2-methyl Propanesulfonic acid 0.31 g was placed in a 100 ml three-necked flask, 15.0 ml of pyridine was added and stirred, then 1.06 ml of triphenyl phosphite was added, and the mixture was heated at 120 ° C. for 6 hours. After completion of the reaction, it was recovered by reprecipitation in 150 ml of ethanol. The obtained polymer was washed with 1N hydrochloric acid for 1 day, then washed by stirring in water for 1 day, and dried under reduced pressure to obtain 0.33 g of polymer.

The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature), Fourier transform-infrared absorption Analysis was performed by (FT-IR) spectrum (Nicolet AVATAR360FT-IR). As a result of IR measurement, the peak at 1695 cm ⁻¹ derived from carboxylic acid decreased, and a new peak derived from the amide group was observed at 1668 cm ⁻¹ .

^From the result of ¹ H-NMR, since the peak derived from methylene having a 2-amino-2-methylpropanesulfonic acid structure is shifted, the obtained polymer is represented by the following chemical formula (60) as a monomer unit. It was confirmed that this was a polyhydroxyalkanoate containing unit.

  Further, it was confirmed that the units of the polyhydroxyalkanoate represented by the chemical formula (60) were 8 mol% of the E unit and 92 mol% of the F unit.

The average molecular weight of the obtained polymer was gel permeation chromatography (GPC; Tosoh HLC-8120, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene. (Conversion). As a result, the number average molecular weight M _n = 8100 and the weight average molecular weight M _w = 12400.

(Example 27)
Condensation reaction of polyhydroxyalkanoate comprising unit represented by chemical formula (40) synthesized in Example 8 and 4-aminobenzenesulfonic acid phenyl ester

  In a nitrogen atmosphere, 0.40 g of 4-hydroxybenzenesulfonic acid, a polyhydroxyalkanoate copolymer (C: 8 mol%, D: 92 mol%) comprising the unit represented by the chemical formula (40) obtained in Example 8 0.51 g of phenyl ester was put in a 100 ml three-necked flask, 15.0 ml of pyridine was added and stirred, 1.06 ml of triphenyl phosphite was added, and the mixture was heated at 120 ° C. for 6 hours. After completion of the reaction, it was recovered by reprecipitation in 150 ml of ethanol. The obtained polymer was washed with 1N hydrochloric acid for 1 day, then washed by stirring in water for 1 day, and dried under reduced pressure to obtain 0.35 g of polymer.

The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature), Fourier transform-infrared absorption Analysis was performed by (FT-IR) spectrum (Nicolet AVATAR360FT-IR). As a result of IR measurement, the peak at 1695 cm ⁻¹ derived from the carboxylic acid decreased, and a new peak derived from the amide group was observed at 1658 cm ⁻¹ .

^From the result of ¹ H-NMR, since the peak derived from the aromatic ring of the 4-aminobenzenesulfonic acid phenyl ester structure is shifted, the obtained polymer is represented by the following chemical formula (61) as a monomer unit. It was confirmed to be a polyhydroxyalkanoate containing unit.

  Further, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (61) was a copolymer of 8 mol% for the E unit and 92 mol% for the F unit.

The average molecular weight of the obtained polymer was gel permeation chromatography (GPC; Tosoh HLC-8120, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene. (Conversion). As a result, the number average molecular weight M _n = 7800 and the weight average molecular weight M _w = 14300.

(Example 28)
Condensation reaction of polyhydroxyalkanoate composed of the unit represented by chemical formula (40) synthesized in Example 8 and 1-naphthylamine-8-sulfonic acid

  In a nitrogen atmosphere, 0.40 g of a polymer synthesized with a polyhydroxyalkanoate copolymer (C: 8 mol%, D: 92 mol%) composed of the unit represented by the chemical formula (40) obtained in Example 8 was used. Naphthylamine-8-sulfonic acid (0.45 g) was placed in a 100 ml three-necked flask, 15.0 ml of pyridine was added and stirred, 1.06 ml of triphenyl phosphite was added, and the mixture was heated at 120 ° C. for 6 hours. After completion of the reaction, it was recovered by reprecipitation in 150 ml of ethanol. The obtained polymer was washed with 1N hydrochloric acid for 1 day, then washed by stirring in water for 1 day, and dried under reduced pressure to obtain 0.33 g of polymer.

The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature), Fourier transform-infrared absorption Analysis was performed by (FT-IR) spectrum (Nicolet AVATAR360FT-IR). As a result of IR measurement, the peak at 1695 cm ⁻¹ derived from the carboxylic acid decreased, and a new peak derived from the amide group was observed at 1658 cm ⁻¹ .

^From the result of ¹ H-NMR, since the peak derived from the aromatic ring having a 1-naphthylamine-8-sulfonic acid structure is shifted, the obtained polymer is represented by the following chemical formula (62) as a monomer unit. It was confirmed to be a polyhydroxyalkanoate containing unit.

  Further, it was confirmed that the units of the polyhydroxyalkanoate represented by the chemical formula (62) were 8 mol% of the E unit and 92 mol% of the F unit.

The average molecular weight of the obtained polymer was gel permeation chromatography (GPC; Tosoh HLC-8120, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene. (Conversion). As a result, the number average molecular weight M _n = 8200 and the weight average molecular weight M _w = 12400.

(Example 29)
Condensation reaction of polyhydroxyalkanoate composed of the unit represented by the chemical formula (43) synthesized in Example 9 and 4-methoxyaniline-2-sulfonic acid

  In a nitrogen atmosphere, 0.40 g of a polyhydroxyalkanoate copolymer (C: 7 mol%, D: 93 mol%) composed of the unit represented by the chemical formula (43) obtained in Example 9 and 4-methoxyaniline-2 -Put 0.21 g of sulfonic acid in a 100 ml three-necked flask, add 15.0 ml of pyridine and stir, then add 0.54 ml of triphenyl phosphite and heat at 120 ° C for 6 hours. After completion of the reaction, it was recovered by reprecipitation in 150 ml of ethanol. The obtained polymer was washed with 1N hydrochloric acid for 1 day, then washed by stirring in water for 1 day, and dried under reduced pressure to obtain 0.32 g of polymer.

The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature), Fourier transform-infrared absorption Analysis was performed by (FT-IR) spectrum (Nicolet AVATAR360FT-IR). As a result of IR measurement, the peak at 1695 cm ⁻¹ derived from the carboxylic acid decreased, and a new peak derived from the amide group was observed at 1658 cm ⁻¹ .

^From the result of ¹ H-NMR, since the peak derived from the aromatic ring having a 4-methoxyaniline-2-sulfonic acid structure is shifted, the obtained polymer is represented by the following chemical formula (63) as a monomer unit. It was confirmed that this was a polyhydroxyalkanoate containing unit.

  Further, it was confirmed that the unit of polyhydroxyalkanoate represented by the chemical formula (63) was a copolymer of 7 mol% for the E unit and 93 mol% for the F unit.

The average molecular weight of the obtained polymer was gel permeation chromatography (GPC; Tosoh HLC-8120, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene. (Conversion). As a result, the number average molecular weight M _n = 6900 and the weight average molecular weight M _w = 10100.

(Example 30)
Esterification reaction of polyhydroxyalkanoate composed of unit represented by chemical formula (50) synthesized in Example 16

  0.30 g of a polyhydroxyalkanoate copolymer (E: 8 mol%, F: 92 mol%) composed of the unit represented by the chemical formula (50) obtained in Example 16 was added to an eggplant flask, and 21.0 ml of chloroform, 7.0 ml of methanol was added to dissolve, and the solution was cooled to 0 ° C. To this, 1.31 ml of a 2 mol / L trimethylsilyldiazomethane-hexane solution (manufactured by Aldrich) was added and stirred for 4 hours. After completion of the reaction, the solvent was removed by an evaporator, and then the polymer was recovered.

  Further, 21.0 ml of chloroform and 7.0 ml of methanol were added to redissolve the polymer, and the solvent was distilled off by an evaporator. This operation was repeated three times.

The polymer collected here was dried under reduced pressure to obtain 0.30 g of polymer. The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature). ^From the result of ¹ H-NMR, since a peak derived from methyl sulfonate is observed at 3 to 4 ppm, the obtained polymer is a polyhydroxyalkanoate containing a unit represented by the following chemical formula (64) as a monomer unit. It was confirmed that.

  Further, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (64) was a copolymer of 8 mol% for the G unit and 92 mol% for the H unit. In addition, the acid value titration using the potentiometric titrator AT510 (manufactured by Kyoto Electronics Co., Ltd.) revealed that the sulfonic acid was methyl sulfonate because no peak derived from sulfonic acid was observed. .

The average molecular weight of the obtained polymer was gel permeation chromatography (GPC; Tosoh HLC-8120, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene. (Conversion). As a result, the number average molecular weight M _n = 15900 and the weight average molecular weight M _w = 24200.

(Example 31)
Esterification reaction of polyhydroxyalkanoate composed of unit represented by chemical formula (58) synthesized in Example 24

  0.30 g of a polyhydroxyalkanoate copolymer (E: 12 mol%, F: 88 mol%) consisting of the unit represented by the chemical formula (58) obtained in Example 24 was added to an eggplant flask, and 21.0 ml of chloroform, 7.0 ml of methanol was added to dissolve, and the solution was cooled to 0 ° C. To this, 1.34 ml of a 2 mol / L trimethylsilyldiazomethane-hexane solution (manufactured by Aldrich) was added and stirred for 4 hours. After completion of the reaction, the solvent was removed by an evaporator, and then the polymer was recovered.

  Further, 21.0 ml of chloroform and 7.0 ml of methanol were added to redissolve the polymer, and the solvent was distilled off by an evaporator. This operation was repeated three times.

The polymer collected here was dried under reduced pressure to obtain 0.31 g of polymer. The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature). ^From the result of ¹ H-NMR, since a peak derived from methyl sulfonate is seen at 3 to 4 ppm, the obtained polymer is a polyhydroxyalkanoate containing a unit represented by the following chemical formula (65) as a monomer unit. It was confirmed that.

  Further, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (65) was a copolymer of 12 mol% for G unit and 88 mol% for H unit.

  In addition, the acid value titration using the potentiometric titrator AT510 (manufactured by Kyoto Electronics Co., Ltd.) revealed that the sulfonic acid was methyl sulfonate because no peak derived from sulfonic acid was observed. .

The average molecular weight of the obtained polymer was gel permeation chromatography (GPC; Tosoh HLC-8120, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene. (Conversion). As a result, the number average molecular weight M _n = 14700 and the weight average molecular weight M _w = 21800.

(Example 32)
Esterification reaction of polyhydroxyalkanoate composed of unit represented by chemical formula (62) synthesized in Example 28

  0.30 g of a polyhydroxyalkanoate copolymer (E: 8 mol%, F: 92 mol%) consisting of the unit represented by the chemical formula (62) obtained in Example 28 was added to an eggplant flask, and 21.0 ml of chloroform, 7.0 ml of methanol was added to dissolve, and the solution was cooled to 0 ° C. To this, 1.34 ml of a 2 mol / L trimethylsilyldiazomethane-hexane solution (manufactured by Aldrich) was added and stirred for 4 hours. After completion of the reaction, the solvent was removed by an evaporator, and then the polymer was recovered.

  Further, 21.0 ml of chloroform and 7.0 ml of methanol were added to redissolve the polymer, and the solvent was distilled off by an evaporator. This operation was repeated three times.

The polymer collected here was dried under reduced pressure to obtain 0.30 g of polymer.
The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature). ^From the result of ¹ H-NMR, since a peak derived from methyl sulfonate is seen at 3 to 4 ppm, the obtained polymer is a polyhydroxyalkanoate containing a unit represented by the following chemical formula (66) as a monomer unit. It was confirmed that.

  Further, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (66) was a copolymer of 8 mol% for the G unit and 92 mol% for the H unit.

In addition, the acid value titration using the potentiometric titrator AT510 (manufactured by Kyoto Electronics Co., Ltd.) revealed that the sulfonic acid was methyl sulfonate because no peak derived from sulfonic acid was observed. . The average molecular weight of the obtained polymer was gel permeation chromatography (GPC; Tosoh HLC-8120, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene. (Conversion). As a result, the number average molecular weight M _n = 7500 and the weight average molecular weight M _w = 11400.

(Example 33)
[Polyester Synthesis Using 5-Ethenyl-2-oxepanone represented by Chemical Formula (67) and ε-caprolactone]

  5-Ethenyl-2-oxepanone represented by the chemical formula (67) 0.31 g (2.0 mmol), ε-caprolactone 1.14 g (10.0 mmol), 0.01 M tin octylate (tin 2-ethylhexanoate) 4.8 ml of toluene solution and 4.8 ml of 0.01M p-tert-butylbenzyl alcohol toluene solution were placed in a polymerization ampule, dried under reduced pressure for 1 hour and purged with nitrogen, and then sealed under reduced pressure. And heated to 150 ° C. to perform ring-opening polymerization. The reaction was terminated after 12 hours and cooled. The obtained polymer was dissolved in chloroform and reprecipitated in 10 times the amount of chloroform required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 0.86 g of polymer.

  As a result of performing NMR analysis under the same conditions as in Example 1 in order to specify the structure of the obtained polymer, it is a polyhydroxyalkanoate copolymer containing a unit represented by the following chemical formula (68) as a monomer unit. It was confirmed. Moreover, it was confirmed that the ratio of the monomer unit is 12 mol% of A unit and 88 mol% of B unit.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 17500, and the weight average molecular weight was Mw = 25400.

(Example 34)
Oxidation reaction of polyhydroxyalkanoate composed of unit represented by chemical formula (68) synthesized in Example 33

  0.50 g of a polyhydroxyalkanoate copolymer (A: 12 mol%, B: 88 mol%) comprising the unit represented by the chemical formula (68) obtained in Example 33 was added to an eggplant flask, and 30 ml of acetone was added. Dissolved. This was placed in an ice bath, 5 ml of acetic acid and 0.40 g of 18-crown-6-ether were added and stirred. Next, 0.32 g of potassium permanganate was slowly added in an ice bath, stirred for 2 hours in an ice bath, and further stirred for 18 hours at room temperature. After completion of the reaction, 60 ml of ethyl acetate was added and 45 ml of water was further added. Sodium bisulfite was then added until the peracid was removed. Thereafter, the liquid property was adjusted to pH = 1 with 1.0 N hydrochloric acid. The organic layer was extracted and washed 3 times with 1.0N hydrochloric acid. After recovering the organic layer, the solvent was distilled off to recover the crude polymer. Next, it was washed with 50 ml of water and 50 ml of methanol, and further washed with 50 ml of water three times, and then the polymer was recovered. Next, it was dissolved in 3 ml of THF, then dissolved in THF, and reprecipitated in 50 times the amount of THF required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 0.42 g of polymer.

  As a result of conducting NMR analysis under the same conditions as in Example 1 to identify the structure of the obtained polymer, it was confirmed that the monomer unit was a polyhydroxyalkanoate containing a unit represented by the following chemical formula (69). It was done.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight Mn was 14300, and the weight average molecular weight Mw was 21500.

  Furthermore, in order to calculate the unit of the obtained polyhydroxyalkanoate, it calculated by methyl-esterifying the carboxyl group in the side chain terminal of polyhydroxyalkanoate using trimethylsilyldiazomethane.

  30 mg of the target polyhydroxyalkanoate was added to a 100 ml eggplant flask, and dissolved by adding 2.1 ml of chloroform and 0.7 ml of methanol. To this was added 0.5 ml of a 2 mol / L trimethylsilyldiazomethane-hexane solution, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the solvent was distilled off and the polymer was recovered. The polymer was recovered after washing with 50 ml of methanol. 29 mg of polyhydroxyalkanoate was obtained by drying under reduced pressure.

  NMR analysis was performed using the same method as in Example 1. As a result, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (69) was a copolymer of 11 mol% for the C unit and 89 mol% for the D unit.

(Example 35)
[Polyester synthesis using tetrahydro-4- (2-propenyl) -2H-pyran-2-one and phenyl lactide (3,6-bis (phenylmethyl) -1,4-dioxane-2,5-dione)]
0.28 g (2.0 mmol) of tetrahydro-4- (2-propenyl) -2H-pyran-2-one represented by the chemical formula (26), 2.96 g (10.0 mmol) of phenyl lactide, 0.01 M octylic acid Tin (2-ethylhexanoic acid) toluene solution 4.8 ml, 0.01M p-tert-butylbenzyl alcohol toluene solution 4.8 ml was charged into a polymerization ampule, dried under reduced pressure for 1 hour, and purged with nitrogen After that, it was sealed under reduced pressure and heated to 180 ° C. to perform ring-opening polymerization. The reaction was terminated after 12 hours and cooled. The obtained polymer was dissolved in chloroform and reprecipitated in 10 times the amount of chloroform required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 2.07 g of polymer. As a result of conducting NMR analysis under the same conditions as in Example 1 to specify the structure of the obtained polymer, it is a polyhydroxyalkanoate copolymer containing a unit represented by the following chemical formula (70) as a monomer unit. It was confirmed. Moreover, it was confirmed that the ratio of the monomer unit is A unit 11 mol% and B unit 89 mol%.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 20500, and the weight average molecular weight was Mw = 26600.

(Example 36)
Oxidation reaction of polyhydroxyalkanoate composed of unit represented by chemical formula (70) synthesized in Example 35

  0.50 g of a polyhydroxyalkanoate copolymer (A: 11 mol%, B: 89 mol%) comprising the unit represented by the chemical formula (70) obtained in Example 35 was added to an eggplant flask, and 30 ml of acetone was added. Dissolved. This was placed in an ice bath, 5 ml of acetic acid and 0.42 g of 18-crown-6-ether were added and stirred. Next, 0.30 g of potassium permanganate was slowly added in an ice bath, stirred for 2 hours in an ice bath, and further stirred for 18 hours at room temperature. After completion of the reaction, 60 ml of ethyl acetate was added and 45 ml of water was further added. Sodium bisulfite was then added until the peracid was removed. Thereafter, the liquid property was adjusted to pH = 1 with 1.0 N hydrochloric acid. The organic layer was extracted and washed 3 times with 1.0N hydrochloric acid. After recovering the organic layer, the solvent was distilled off to recover the crude polymer. Next, it was washed with 50 ml of water and 50 ml of methanol, and further washed with 50 ml of water three times, and then the polymer was recovered. Next, it was dissolved in 3 ml of THF, then dissolved in THF, and reprecipitated in 50 times the amount of THF required for dissolution. The precipitate was collected and dried under reduced pressure to obtain 0.42 g of polymer.

  As a result of conducting NMR analysis under the same conditions as in Example 1 to identify the structure of the obtained polymer, it was confirmed that the monomer unit is a polyhydroxyalkanoate containing a unit represented by the following chemical formula (71). It was done.

  The average molecular weight of the obtained polyhydroxyalkanoate was evaluated by gel permeation chromatography (GPC: Tosoh HLC-8220, column: Tosoh TSK-GEL Super HM-H, solvent: chloroform, polystyrene conversion). . As a result, the number average molecular weight was Mn = 16800, and the weight average molecular weight was Mw = 22300.

  Furthermore, in order to calculate the unit of the obtained polyhydroxyalkanoate, it calculated by methyl-esterifying the carboxyl group in the side chain terminal of polyhydroxyalkanoate using trimethylsilyldiazomethane.

  30 mg of the target polyhydroxyalkanoate was added to a 100 ml eggplant flask, and dissolved by adding 2.1 ml of chloroform and 0.7 ml of methanol. To this was added 0.5 ml of a 2 mol / L trimethylsilyldiazomethane-hexane solution, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the solvent was distilled off and the polymer was recovered. The polymer was recovered after washing with 50 ml of methanol. 29 mg of polyhydroxyalkanoate was obtained by drying under reduced pressure.

  NMR analysis was performed using the same method as in Example 1. As a result, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (71) was a copolymer of 11 mol% for the C unit and 89 mol% for the D unit.

(Example 37)
Condensation reaction of polyhydroxyalkanoate composed of the unit represented by chemical formula (71) synthesized in Example 36 and 2-aminobenzenesulfonic acid

  In a nitrogen atmosphere, 0.40 g of a polyhydroxyalkanoate copolymer (C: 11 mol%, D: 89 mol%) comprising the unit represented by the chemical formula (71) obtained in Example 36, 2-aminobenzenesulfonic acid 0.26 g was placed in a 100 ml three-necked flask, 15.0 ml of pyridine was added and stirred, 0.77 ml of triphenyl phosphite was added, and the mixture was heated at 120 ° C. for 6 hours. After completion of the reaction, it was recovered by reprecipitation in 150 ml of ethanol. The obtained polymer was washed with 1N hydrochloric acid for 1 day, then washed by stirring in water for 1 day, and dried under reduced pressure to obtain 0.34 g of polymer.

The structure of the obtained polymer was determined by ¹ H-NMR (FT-NMR: Bruker DPX400; resonance frequency: 400 MHz; measurement nuclide: ¹ H; solvent used: heavy DMSO; measurement temperature: room temperature), Fourier transform-infrared absorption Analysis was performed by (FT-IR) spectrum (Nicolet AVATAR360FT-IR). As a result of IR measurement, the peak at 1695 cm ⁻¹ derived from the carboxylic acid decreased, and a new peak derived from the amide group was observed at 1658 cm ⁻¹ . ^From the result of ¹ H-NMR, since the peak derived from the aromatic ring having a 2-aminobenzenesulfonic acid structure is shifted, the obtained polymer has a unit represented by the following chemical formula (72) as a monomer unit. It was confirmed to be a polyhydroxyalkanoate containing.

  Further, it was confirmed that the unit of the polyhydroxyalkanoate represented by the chemical formula (72) was a copolymer of 11 mol% for the E unit and 89 mol% for the F unit.

The average molecular weight of the obtained polymer was gel permeation chromatography (GPC; Tosoh HLC-8120, column; Polymer Laboratories PLgel 5μ MIXED-C, solvent; DMF / LiBr 0.1% (w / v), polystyrene. (Conversion). As a result, the number average molecular weight M _n = 16000 and the weight average molecular weight M _w = 22700.

  According to the present invention, the side chain has a novel polyhydroxyalkanoate containing a vinyl group which is a reactive group in the molecule, a novel polyhydroxyalkanoate containing a carboxyl group in the molecule, and an amide group and a sulfonic acid group. A novel polyhydroxyalkanoate containing a unit in the molecule and a method for producing the same are provided. As a result, a novel polyhydroxyalkanoate having a vinyl group or a carboxyl group can be introduced into a functional material because a functional functional group can be introduced using the reactive group. Furthermore, polyhydroxyalkanoates that contain a carboxyl group or a unit having an amide group and a sulfonic acid group in the molecule are excellent in melt processability and are also excellent in biocompatibility due to their hydrophilicity. It can be expected to be used as a soft member for use.

Claims (4)

A polyhydroxyalkanoate comprising one or more units represented by the chemical formula (1) in a molecule.

(Wherein, R .R ₁ representing a -A ₁ -SO ₂ R ₁ represents OH, a halogen atom, ONa, .R _1a and A ₁ is OK or OR _1a each independently represents a substituted or unsubstituted A group having an aliphatic hydrocarbon structure, a substituted or unsubstituted aromatic ring structure, or a substituted or unsubstituted heterocyclic structure, wherein l is an integer selected from 1 to 4; Is an integer selected from 1 to 4, and m is an integer selected from 0 to 8. When a plurality of units are present, R, R ₁ , R _1a , A ₁ , l, m and n Represents the above meaning independently for each unit.) 2. The polyhydroxyalkano according to claim 1, wherein the unit represented by the chemical formula (1) includes at least one unit represented by the chemical formula (2), the chemical formula (3), the chemical formula (4A), or (4B) in the molecule. Eight.

Wherein R ₂ is OH, a halogen atom, ONa, OK or OR _2a . R _2a is a linear or branched alkyl group having 1 to 8 carbon atoms, or a substituted or unsubstituted phenyl group. A ₂ represents a linear or branched alkylene group having 1 to 8 carbon atoms, l is an integer selected from 1 to 4, and n is an integer selected from 1 to 4. M is an integer selected from 0 to 8. When a plurality of units are present, A ₂ , R ₂ , R _2a , l, m and n are as defined above independently for each unit. Represents.)

(In the formula, R _3a , R _3b , R _3c , R _3d and R _3e are each independently SO ₂ R _3f (R _3f is OH, a halogen atom, ONa, OK or OR _3f1 (R _3f1 is A linear or branched alkyl group having 1 to 8 carbon atoms, or a substituted or unsubstituted phenyl group.)), Hydrogen atom, halogen atom, alkyl group having 1 to 20 carbon atoms, 1 to 20 carbon atoms Alkoxy group, OH group, NH ₂ group, NO ₂ group, COOR _3g (R _3g represents any one of H atom, Na atom and K atom), acetamide group, OPh group, NHPh group, CF ₃ group, Represents a C ₂ F ₅ group or a C ₃ F ₇ group (Ph represents a phenyl group), at least one of these groups is SO ₂ R _3f , and l is an integer selected from 1 to 4 N is an integer selected from 1 to 4, and m is selected from 0 to 8 Is a number. When multiple units _{exist, R 3a, R 3b, R} 3c, R 3d, R 3e, R 3f, R 3f1, R 3g, l, m and n are, independently for each unit Represents the above meaning.)

Wherein R _4a , R _4b , R _4c , R _4d , R _4e , R _4f and R _4g are each independently SO ₂ R _4o (R _4o is OH, halogen atom, ONa, OK or OR _4o1 (R _4o1 is a linear or branched alkyl group having 1 to 8 carbon atoms, a substituted or unsubstituted phenyl group)), a hydrogen atom, a halogen atom, an alkyl group having 1 to 20 carbon atoms , C 1-20 alkoxy group, OH group, NH ₂ group, NO ₂ group, COOR _4p (R _4p represents any one of H atom, Na atom and K atom), acetamide group, OPh group, NHPh group , CF ₃ group, C ₂ F ₅ group or C ₃ F ₇ group (Ph represents a phenyl group), at least one of these groups is SO ₂ R _4o , and l is 1 to 4 N is an integer selected from 1 to 4, m is an integer selected from 1 to 4, and m is selected from 0 to 8. The integers. When multiple units _{exist, R 4a, R 4b, R} 4c, R 4d, R 4e, R 4f, R 4g, R 4o, R 4o1, R 4p, l, m and n are The above meaning is expressed independently for each unit.)

(Wherein R _4h , R _4i , R _4j , R _4k , R _4l , R _4m and R _4n are each independently SO ₂ R _4o (R _4o is OH, halogen atom, ONa, OK or OR _4o1. (R _4o1 is a linear or branched alkyl group having 1 to 8 carbon atoms, a substituted or unsubstituted phenyl group)), a hydrogen atom, a halogen atom, an alkyl group having 1 to 20 carbon atoms , C 1-20 alkoxy group, OH group, NH ₂ group, NO ₂ group, COOR _4p (R _4p represents any one of H atom, Na atom and K atom), acetamide group, OPh group, NHPh group , CF ₃ group, C ₂ F ₅ group or C ₃ F ₇ group (Ph represents a phenyl group), at least one of these groups is SO ₂ R _4o , and l is 1 to 4 N is an integer selected from 1 to 4, m is an integer selected from 1 to 4, and m is selected from 0 to 8. The integers. When multiple units _{exist, R 4h, R 4i, R} 4j, R 4k, R 4l, R 4m, R 4n, R 4o, R 4o1, R 4p, l, m and n are The above meaning is expressed independently for each unit.) The polyhydroxyalkanoate according to claim 1 or 2 , further comprising a unit represented by the chemical formula (7) in the molecule.

(R ₇ is a linear or branched alkylene group having 1 to 11 carbon atoms, an alkyleneoxyalkylene group (each alkylene group is independently an alkylene group having 1 to 2 carbon atoms) or aryl. (It may be an alkylidene group having 1 to 5 carbon atoms.) When a plurality of units are present, R ₇ represents the above meaning independently for each unit. Including a unit represented by the chemical formula (1), comprising a step of subjecting a polyhydroxyalkanoate comprising a unit represented by the chemical formula (11) to at least one amine compound represented by the chemical formula (13) to a condensation reaction. Process for producing polyhydroxyalkanoate.

(In the formula, R ₁₁ is hydrogen or a group forming a salt. L is an integer selected from 1 to 4, n is an integer selected from 1 to 4, and m is 0 to 0. (It is an integer selected from 8. When there are a plurality of units, l, m, n and R ₁₁ represent the above meanings independently for each unit.)

Wherein R ₁₃ is OH, a halogen atom, ONa, OK or OR _13a . R _13a and A ₃ are each independently a substituted or unsubstituted aliphatic hydrocarbon structure, substituted or unsubstituted aromatic In the case where a plurality of units are present, R ₁₃ , R _13a and A ₃ each independently have the above meaning for each unit. To express.)

(Wherein, .R ₁ R is representative of a -A ₁ -SO ₂ R ₁ is OH, halogen atom, ONa, OK, or is OR _1a .R _1a and A ₁ each independently represents a substituted or unsubstituted aliphatic Represents a group having an aromatic hydrocarbon structure, a substituted or unsubstituted aromatic ring structure, or a substituted or unsubstituted heterocyclic structure, wherein l is an integer selected from 1 to 4, and n is from 1 to 4 M is an integer selected from 0 to 8. When there are a plurality of units, R, R ₁ , R _1a , A ₁ , l, m and n are for each unit. Independently represents the above meaning.)