JPS5910672B2 - Sesquiterpene derivatives and their production method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel sesquiterpene derivative and a method for producing the same.

The compound of the present invention is a sesquiterpene derivative represented by the formula: (■)゛, H CH3CH3 , and is a novel compound that has not been described in any literature and has the physical properties described in the Examples below.

The compound () of the present invention is useful as an important intermediate for conversion into various physiologically active substances having similar skeletons.

For example, the compound () of the present invention can be used as a compound of Conferteiforin (Confertiforin), which has already been isolated as a natural product.
ifOlin) (a) [H. H. Appel. etal
;J. Chem. SOc. , 1960, 4685]
(Patent Application No. 53-11035)
9), and also Barbaganal [A
[Chem.
cidial) [Also known as: Cinna
mOdial)] [B], Polygodial (POlyg
Odial) [Also known as: TadeOnal
)] [C] and skin fungi (e.g., TrycOphy
Cinnamolide (CinnamOllde) [D
] [L. Can Onicasetal: Tetrahe
drOnl25, 3895 (1969)].

In addition, the compound 0 () of the present invention is derived from isodorimenine (Iqinshi 1menine), which has already been isolated as a natural product.
) (1) [J. Clem. SOc. , P. 4685(
(1960)], and further can be similarly derived into the above-mentioned useful substances. Next, a synthesis example of barbaganal [A] will be described.

In this step, the starting material 7-oxoisodrimenine (7-oxoisodrimenine) can be obtained easily and in high yield by treating the isodorimenine with an oxidizing agent, especially chromic acid [H. H. Appel, Eta
l;J. Chem. SOc. , 4685 (1960)], and the isodorimenine can be synthesized in a short process from readily available β-ionone (β-10nene) (see Japanese Patent Application No. 110359/1982).

To explain the above process, the starting material 7-oxoisodorimenine is first induced into a ketal form, and then a ketone form, diacetate form, epoxy form, triol form, silyl form, carbonate form, alcohol form, aldehyde form, and ketal form. , a diol form and an aldehyde form, respectively, to synthesize barganal.

To explain this step by step, first, the starting material 7-oxoisodorimenine (2) is treated with a dialcohol and an organic acid and refluxed to obtain the ketal (I) in high yield.

The obtained ketal form C can be reacted with a reducing reagent in a tertiary organic solvent to lead to the ketone form (4) in high yield.

By reacting the obtained ketone body (4) with an acetylating agent in a solvent, the diacetate body (5) can be obtained in high yield.

Epoxy compound Q can be obtained in high yield by treating the obtained diacetate 5) with a peroxide in the presence of an aqueous alkali solution.

The obtained epoxy body (6) is reacted with hydrazine hydrate to introduce a double bond to obtain a triol body (η).

The obtained triol compound (7) is reacted with imidazole and trialkylsilyl chloride to obtain a silyl compound (8) in which the hydroxyl group of the aryl group is protected.

The obtained silyl compound (8) is refluxed with phosgene or carbonylimidazole to obtain a carbonate compound (9YS) in which glycol is protected with carbonate in a high yield.

By treating the obtained carbonate form (9) with an organic acid, the silyl is returned to alcohol, and the alcohol form (9) is converted into an alcohol form.
) can be obtained quantitatively.

When the obtained alcohol is reacted with an oxidizing agent, the aldehyde is obtained in high yield.

By treating the obtained aldehyde (auto) with a dialcohol and an organic acid to further protect it with an acetal, a ketal σz that is stable to alkali can be obtained. By treating the obtained ketal compound with an alkali, diol compound 1 can be obtained in high yield.

The obtained diol is reacted with an oxidizing agent under basic or neutral conditions to obtain an aldehyde. When the aldehyde (auto) obtained in this way is reacted with an organic acid, the above-mentioned barburganal [A] is obtained. Barberganal [A] synthesized in this manner completely matches the physical properties of the natural product Barberganal.

The inventors of the present application previously developed a method for synthesizing sesquiterpene compounds such as conferteiforin and isodorimenine from l-abietic acid [96th Annual Meeting of the Pharmaceutical Society of Japan (19
1976) Lecture Abstracts Volume 197, 97th Annual Meeting (
1977) Collection of lecture abstracts, separate volume, page 197, patent application 1977
-38628 (Japanese Unexamined Patent Publication No. 53-124256),
[Refer to Japanese Patent Application Laid-Open No. 53-34768], as a result of intensive research on the synthesis method of the above sesquiterpene compound, we found that conferteiforin, The present invention was completed by discovering a method for synthesizing sesquiterpene compounds such as isodomenine, obtaining the novel compound () of the present invention in the process, and establishing a method for its production.

The compound () of the present invention is produced by the following method.

First, the furan compound (Xl), which is the starting material of the present invention, is a new compound synthesized by the inventor of the present invention, and can be obtained, for example, from β-ionone (1) by the following process.

That is, β-ionone (1) was catalytically reduced by a known method using a catalyst such as Raney Nickel to obtain dihythro β-yonone 02) [J. KandeletalA
nn,. Chem. , 11, 73 (1939), COm
pt. rend. , 205, 994 (1937), and when this is reacted with CH(0CH3)3 in the presence of an acid such as HClO4, compounds with increased C1-units, tetramethoxy compound (), aldehyde compound (), ketone compound ( V) is obtained.

(V) is () with pyridine-HBr-H2O or (
) can also be obtained by treating with pyridine-HBr. The obtained ketone body (V) is treated with an α-haloacid ester, for example, ClC
Darzen (Darzen) using H2COOCH,
s) When condensation is performed, an epoxy compound () is obtained.

When this is heat-treated, carboxyfuran* () (R=
CH3) is obtained. Obtained carboxyfuran compound ()
is to obtain a furanocarboxylic acid (X) (R=H) with A/B trans-coordination by a combination of Friedel-Crafts reaction using a Lewis acid catalyst such as SnCl4, AICl3, etc. and a hydrolysis step. I can do it. This was then carried out in the presence of quinoline-Cu. When heat-treated in the mouth, decarboxylation easily progresses, and the starting material of the present invention, the furan compound (
XI) can be obtained. According to the present invention, the furan compound (XI) is used as a starting material, and an oxidizing agent such as P
When b(0C0CH3)4 is stirred in a solvent such as benzene or acetic acid, the target compound of the present invention, diacetate (), is obtained.

The reaction temperature and reaction time at this time were 0 to 30°C, respectively.
1 to 5 hours is appropriate. The present invention will be explained in detail below by way of examples.

Example Furan compound (XI) 0.860f was dissolved in 20 g of dry benzene, Pb(0C0CH3)4 (recrystallized from acetic acid and dried with P2O, MW = 443.39
) 1.728f7 (1m.m01) and stir at room temperature.
Stir for an hour.

After the reaction was completed, the contents were subjected to column chromatography using 50y of silica gel, and 1.190t of a single oily substance was obtained from the eluate of n-hexane:ethyl acetate = 5:1.
(90%). If left alone, some of this will crystallize. [Physical properties of ()] GC-MS: M+=336C1, m/e as H2805336: 276=M+-CH, COOH=336IR
(CCl4): νNlaxl76Ol222ONMR(
60MH2, CDCl3): δ0.93S6H(4-G
emMe2) 1.18S3H (10-Me) 2.10S6H (11- 14-0C0CH3): [4
! ``1 SlHlH] (11-14-H) Reference Example 6.03 t of the diacetate compound () obtained in Example was heated in an oil bath,
After heating at 00°C for 40 minutes, it crystallizes when cooled.

(A mixture of (a) and (1) in a ratio of 4:1) When this is recrystallized from n-hexane, colorless prism crystals ((a) and (1>f
) Mixture) 2.767f7 is obtained. Mother liquor 1.295r was subjected to column chromatography using silica gel 30r, and n-
Crystals ((a
) and (1) mixture) 0.971f (total 3.738f
7 (89%)). By repeating recrystallization from n-hexane, the crystals are pure (±)-conferteifolin (
a) is obtained. [Physical properties of (a)] GC-MS: M+=234C15H220,=234 for each S3H(4-GemMe2) 1.17S3H(10-Me) 4.66-4.76m. 2H (7-H2) Furthermore, IR.
．． NMR. GC-MS was consistent with the natural product (+)-conferteiforin.

[Physical properties of (1)] GC-MS: M+=2 as Cl5H22O2=234
34, GC-MS was consistent with the natural product (+)-isodorimenine.

Claims (1)

[Claims] 1. A compound represented by formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼. 2 Formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ Formula characterized by treating the compound represented by lead tetraacetate: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ A method for producing the compound represented by.