JPS596313B2 - Method for producing sesquiterpene derivatives - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention uses a compound represented by the formula: ゛゛, H H3CCH3 as a starting material, which is treated with an oxidizing agent and then heat-treated to form a compound represented by the formula: ゛・, H H3CCH3. The present invention relates to a method for producing sesquiterpene derivatives, which is characterized in that a compound is obtained.

ConfertifOlin, the target compound obtained by the present invention, has been isolated as a natural product [H. H. Appel. J. D. CON
nOlly,. K. H. Overt Onand (Inp
art)R. M. BOndJ. Chem. SOc. ,1
See 96014685. ] Although it does not have any significant physiological activity by itself, it is thought to be useful as an important intermediate in the conversion to various physiologically active substances with similar skeletons.
As described below, there are various types of Torimus sesquiterpene compounds with unique structures, and compounds that can be easily derived from the above-mentioned Conferteiforin include, for example, the night robber moth (Africana).
A potent antifeedant (Ant) against rnvwOrm)
Barbaganal (War
burganal) [A], Agandencidial (also known as CinnamOdial) [B], Polygodial (POlygOdial) [also known as Tade Onal (
TadeOnal)] [C], [1. Kub0. yue
-Weilee,. M. Pettei,. F. Pilk
iewiczandK. NalaLnishi,. Ch
em. COmm. , 1976, 1013] and skin fungi (e.g., TrycOpnytOn, .MicrO
Cinnamolide (CinnamOllde) [D], [L. CanO
nicalA. Corbella,. P. GaribO
ldi,,G. TommiandJ. Krepinsk
i AndG. Ferrari,. C. Casagra
nde. ．． TetrahedrOnl? Dan, 3895 (
1969)].

The inventors of the present application previously discovered that conferteiforin and isodorimenine (SOdrimcnin) were synthesized from l-abietic acid.
), we developed a method for synthesizing sesquiterpene compounds such as (
96th Annual Meeting of the Pharmaceutical Society of Japan (1976) Lecture Abstracts Volume 197, 97th Annual Meeting of the Pharmaceutical Society of Japan (1977) Lecture Abstracts Volume 197, Specification of Japanese Patent Application No. 52-38628, JP-A (Refer to Publication No. 53-34768), and as a result of intensive research on a method for separately synthesizing the above sesquiterbene compound, we found that easily available β-ionone (β-10nene) (1)
The present invention was completed based on the knowledge that sesquiterpene compounds such as conferteiforin and isodorimenine can be synthesized in extremely short steps.

First, the furan compound (auto) which is the starting material of the present invention is a new substance synthesized for the first time by the inventors of the present application, and can be obtained, for example, from the above-mentioned β-ionone (1) in the following manner.

That is, β-ionone (1) was catalytically reduced by a known method using a solvent such as Raney and Nickel to obtain dihydro β-ionone (2) [J. KandeletalAn
n. Chem. , 11.73 (1939), Comp
t. rend. , 205, 994 (1937), and when this is reacted with CH(0CH3)3 in the presence of an acid such as HCl4, compounds with increased C1-units, tetramethoxy compound (3), aldehyde compound (4), ketone body(
5) is obtained.

(5) is (3) with pyridine-HBr-H2O or (
4) can also be obtained by treating with pyridine-HBr. The obtained ketone body (5) is treated with an α-haloacid ester, for example, Cl
Darze (Darze) using CH2COOCH3
ns) An epoxy compound (6) that undergoes condensation is obtained. When this is heat-treated, carboxyfuran compound (7) (R=CH
3) is obtained. The obtained carboxyfuran compound (7) is produced by a combination of a Friedel-Crafts reaction using a Lewis acid catalyst such as SnCl4/AlCl3 and a hydrolysis step, to form a furanocarboxylic acid AI with A/B trans-coordination.
(R=H) can be obtained. When this is then heat-treated in the presence of quinoline-Cu, decarboxylation easily proceeds to yield the furan compound (self) that is the starting material of the present invention. According to the present invention, the furan body (self) is used as a starting material, and this is used as an oxidizing agent, such as Pb (0C0CH
, ) 4 is stirred in a solvent such as benzene or acetic acid to obtain a diacetate.

The reaction temperature and reaction time at this time were 0 to 30℃, 1
~5 hours is appropriate. Next, the obtained diacetate compound (
When heat-treating the mixture, a mixture (approximately 3:1) of conferteiforin (self) and isodorimenine (self) is obtained,
By repeating this recrystallization using n-hexane or the like, pure (e)-conferteiforin can be obtained.

The heating temperature and heating time at this time are 180-220℃, 30℃
Appropriate time is 1 minute to 1 hour. Please note that (2) is a new substance.

The present invention will be explained in detail below using examples.

Example: 0.860 t of furan compound (al) was dissolved in 20 ml of dry benzene, Pb(0C0CH3)4 (after recrystallization from acetic acid)
Dry with 2O5, MW=443.39) 1.72
Add 8t (1 m.m01) and stir at room temperature for 3 hours.

After the reaction was completed, the contents were subjected to column chromatography using silica gel 50V to obtain a single oily substance (1.190f (90%)) from the eluate of n-hexane:ethyl acetate = 5:1.
get. If left alone, some of this will crystallize. Example The diacetate compound A36 obtained in Example 1. After heating O3l in an oil bath at 200°C for 40 minutes, it crystallizes when cooled (a 4:1 mixture of 13 and (self)). When this is recrystallized from n-hexane, colorless prism crystals (Q3 and a◆ mixture) to obtain 2.767f.

1.295 t of mother liquor was subjected to column chromatography using 30 t of silica gel, and 0.971 t of crystals (mixture of (13 and (self)) were obtained from the eluate of n-hexane:ethyl acetate = 2:1.
(3.738t (89%) in total) was obtained. By repeating recrystallization from n-hexane, pure confertifluorin 03 can be obtained. [Physical properties of l] As 234, it was consistent with nfuerteiforin.

Claims (1)

[Claims] 1 Formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ A compound represented by the following is used as a starting material, which is treated with lead tetraacetate and then heat-treated to form the formula: ▲Mathematical formula, chemical formula, etc. , Tables, etc. ▼ A method for producing sesquiterpene derivatives, which is characterized by obtaining a compound represented by .