JPS5932470B2 - Sesquiterpene compounds and their production methods - Google Patents

Description

[Detailed description of the invention] The present invention has the structural formula: o゛GO O-C-0CH2CCl3 -, n H3C--CH.

The present invention relates to a novel sesquiterpene compound represented by and a method for producing the same.

The compounds of the present invention are derived from the natural substance cinnamodial (Ci
nnamOdial) [Also known as: Ugandan Odial (
It is an important intermediate in the total synthesis of Cinnamosmolide) or CinnamOsmOlide.

These natural substances are derived from the African plant Barbagia (War).
burgia) or CinnamOsm
It was isolated as an extract component from a), and its structural formula has also been determined. Cinnamodiar is a Night Thief Moth (ArmywO
A powerful antifeedant (Antifeed) against
It is a useful substance that acts as ant) (Chem.C
Omm. (1976)], and cinnamosmolide is known as one of the useful substances that exhibits antifungal activity against skin fungi such as Trichophyton and Microsporum among the above extract components. ing. [L. Can
Onica,. A. Corbella,. P. Gari
bOldi,. G. JOmmi,. J. Kr and Pins
ki,. G. Ferrarian and C. Casagra
ndeTetrahe total 0n15, 3895 (1969
)reference〕.

The present inventors, taking the opportunity of determining the structure of the natural substance, conducted extensive research on the production of the substance by a synthetic method, and as a result, using 8-hydroxymethyl carbonate (1) derived from isodomenine as a starting material, cinnamodi The present invention was completed in the process of total synthesis of R or cinnamosmolide.

The compound of the present invention is useful as an important intermediate in the next step in the total synthesis of cinnamodial or cinnamosmolide.

(However, in the formula, Ac represents COCH3.

) In the above step, the starting material 8-hydroxymethyl carbonate (1) is a new compound synthesized for the first time by the present inventors, for example, IsOdrimenin, which is isolated as a natural product.
n) [J. Chem. SOc. , P. 4685 (196
0)] by the following steps. In addition, the above-mentioned isodorimenine is provided by the inventors of the present application.
Total synthesis has already been achieved as a sesquiterpene derivative derived from l-abietic acid, and it is easily available [Japanese Patent Application No. 5238628 (Japanese Unexamined Patent Publication No. 53-124)
See Publication No. 256)].

In addition, the inventors of the present invention have also succeeded in synthesizing isodorimenine from easily available β-ionone (β-10n0ne) in an extremely short process (Japanese Patent Publication No. 59-63
(See Publication No. 13). To explain the above steps for the total synthesis of cinnamodial or cinnamosmolide, the starting material 8-hydroxymethyl carbonate (1) is first induced into the trichloroethoxycarbonyl compound (2), and then the cinnamodial compound (3), 6-hydroxy form (4), 6-acetoxy form (5), alcohol (6), carboxylic acid (7)
, cinnamosmolide (9) can be synthesized by successive conversion to 6β-hydroxylactone (8). In addition, cinnamodial (self) can be synthesized by sequentially converting the alcohol (6) into an aldehyde (self), a ketal (self), a diol (self) and an α-hydroxyaldehyde (self). can. This will be explained below in accordance with the steps. First, the starting material 8-hydroxymethyl carbonate (1) is reacted with β.β.β-trichloroethoxycarbonyl chloride to obtain trichloroethoxycarbonyl compound (2) in a good yield. The obtained trichloroethoxycarbonyl compound (2) was reacted with an oxidizing agent to obtain the engineered non compound (2).
3) is obtained. The obtained echonone form (3) can be reacted with a reducing reagent in an organic solvent to lead to the 6-hydroxy form (4).

The 6-acetoxy compound (5) can be obtained in high yield by reacting the obtained 6-hydroxy compound (4) with an acetylating agent in a solvent.

The obtained 6-acetoxy compound (5) is treated with zinc in a solvent to remove trichlorethoxycarbonylation, and the alcohol compound (6) is quantitatively obtained.

When the obtained alcohol (6) is sufficiently reacted with an oxidizing agent, carboxylic acid (7) can be obtained almost quantitatively. When the obtained carboxylic acid (7) is treated with an alkali and then treated with an acid, a 6β-hydroxylactone (8) is obtained. By reacting this 6β-hydroxylactone (8) with an acetylating agent, cinnamosmoridene {((
9) can be obtained in high yield.

This completely matches the physical properties of natural cinnamosmolide. Furthermore, when the alcohol (6) is quickly reacted with an oxidizing agent, the aldehyde (self) can be obtained in high yield.

The obtained aldehyde (AO) is further treated with a dialcohol and an organic acid to protect it with an acetal, thereby obtaining an alkali-stable ketal.

By treating the obtained ketal 00 with an alkali, the diol (auto) can be obtained in high yield.

The obtained diol (auto) is reacted with an oxidizing agent under basic or neutral conditions to obtain an α-hydroxyaldehyde (auto). When this α-hydroxyaldehyde (auto) is heated and refluxed with an organic acid, cinnamodial (auto) is obtained.

This completely matches the physical properties of the natural product cinnamodial.

The compound of the present invention can be produced by the following method.

That is, by reacting 8-hydroxymethyl carbonate (1), which is the starting material of the present invention, with β.β.β trichloroethoxycarbonyl chloride, the target trichloroethoxycarbonyl compound (2) can be obtained in a good yield.
In this case, pyridine, triethylamine, etc. can be used as the solvent, but particularly excellent results are obtained when pyridine-ether is used.

In the above reaction, a reaction temperature of room temperature is sufficient, and a suitable reaction time of about 1 to 4 hours.

The present invention will be specifically explained below with reference to Examples, and the target compound (2) is a new compound. Example 1 (1) Dissolve 280W19 (1.00 mm01) in 10 ml of ether, add 2 ml of pyridine, and dissolve β under ice cooling.
・β・β-Trichloroethoxycarbonyl chloride 2
Drop 68μ,e (2.00mm01).

After dropping, return to room temperature, stir for 1 hour, extract with ether, and add H2O.
, 5% HCI aqueous solution, washed with saturated saline, anhydrous MgSO
After drying in step 4, the solvent was distilled off and subjected to silica gel column chromatography.
Crystals 439~ (yield 96%) of 2) are obtained. [Physical properties of (2)]

Claims (1)

[Claims] 1. A sesquiterpene compound represented by the structural formula ▲ Numerical formula, chemical formula, table, etc. available▼. 2 Structural formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ The compound represented by β, β, β-trichloroethoxycarbonyl chloride (ClCOOCH_2CCl_3
) to obtain a compound represented by the structural formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼.