JPS5932469B2 - Sesquiterpene compounds and their production method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel sesquiterpene compound represented by the structural formula: -H3CCH30C0CH3 and a method for producing the same.

The compounds of the present invention are derived from the natural substance cinnamosmolide (C
It is an important intermediate in the total synthesis of innamosmolide.

Cinnamosmolide is a natural substance isolated as an extract component from the African plant Cinnamosma (Cinnamosnla), and its structural formula has also been determined.

Extracts of these plants exhibit antifungal activity against skin fungi, such as Trichophyton and Microsporum, and cinnamosmolide is one of their active ingredients.
L. CanOnica. A. Corbella. P. G
aribOldilG. JOmmi. J. Kr and Pin
ski. G. Ferrarian and C. Casagra
ndeTetrahedrOnZ''-, 3895r★(
1969)].

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

The compound of the present invention is useful as an important intermediate in the next step in the total synthesis of cinnamosmolide. Droxymethyl carbonate (l) is a new compound synthesized for the first time by the present inventors,
For example, as a natural product, isolated isodorimenin (
Is Odrimenin) [J. Chem. SOc. ,
P. 4685 (1960)] by the following process.

In addition, the above-mentioned isodorimenine is l-
Total synthesis has already been achieved as a sesquitel★1 pen derivative derived from abietic acid, and it is easily available.

[Patent Application No. 52-38628 (Japanese Patent Application No. 12425/1982)
See Publication No. 6)]. In addition, easily available β-ionone (β-ionone)
The inventors of the present application have also succeeded in synthesizing isodorimenine from (IOnOne) in an extremely short process (see Japanese Patent Publication No. 59-6313). To explain the steps involved in the total synthesis of cinnamosmolide, the starting material 8-hydroxymethyl carbonate (1) is first induced into the trichloroethoxycarbonyl compound (2), and then the enoone compound (3), 6 -Hydroxy rain 4), 6-acetoxy form 5), alcohol rain 6), carboxylic acid (7)
, 6β-hydroxylactone (8) can be successively converted to synthesize the desired cinnamosmorite' (9).

This will be explained below in accordance with the steps.

First, 8-hydroxymethyl carbonate (1) as a starting material is reacted with β·β·β-trichloroethoxycarbonyl chloride to obtain trichloroethoxycarbonyl compound (2) in a good yield.

The obtained trichloroethoxycarbonyl compound (2) is reacted with an oxidizing agent to obtain a non-containing compound (3). 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) is obtained almost quantitatively. When the obtained carboxylic acid (7) is treated with an alkali and then with an acid, a 6β-hydroxylactone (8) is obtained. Next, cinnamosmolide (9) can be obtained by reacting the obtained 6β-hydroxylactone (8) with an acetylating agent.

This completely matches the physical properties of the natural product cinnamosmolide. The compound of the present invention can be produced by the following method.

That is, by sufficiently reacting the alcohol compound 6) of the starting material of the present invention with an oxidizing agent, the carboxylic acid (7) is
Obtained almost quantitatively. As an oxidizing agent, John's (
JOnes) reagent is optimal, and acetone is particularly effectively used as a solvent. Although the reaction temperature and reaction time are not particularly limited, the reaction proceeds sufficiently at room temperature and about 1 to 2 hours, respectively. The present invention will be specifically explained below using reference examples and examples.

In addition, compounds (2), (3), (4), (5), (6)
, (7) are all new compounds.

Reference example 1 (1) 280 watts (1.00mm01) to ether 10
ml, add 2 ml of pyridine, and add β, β,
β-trichloroethoxycarbonyl chloride 268μ
1 (2.00 mm 01).

After dropping, return to room temperature, stir for 1 hour, extract with ether, and add H2O.
, 5% aqueous HCl solution, washed with saturated saline, anhydrous MgSO
After drying in step 4, the solvent was distilled off and subjected to silica gel column chromatography to obtain crystals 439~ (yield 96%) of (2) from the fraction eluted with hexane-ethyl acetate (3:1). (2)
Dissolve 228W (0.500mm01) in 5ml of AcOH, add CrO325OW (2.50mm01),
Stir at room temperature for 24 hours.

After the reaction, H2O was added and extracted with ether, H2O, saturated Na
Washing with an aqueous HCO3 solution and saturated brine, drying with anhydrous MgSO4, and distilling off the solvent yielded an oily product of 192η.
This was subjected to silica gel column chromatography, and from the hexane-ethyl acetate (5:1 to 3:1) eluate, (3)
0 w (yield 64%) was obtained. (3) 1.409rf9(
3.00 mm01) was suspended in 60 ml of anhydrous ether,
Zn(BH4)2 ether solution (34 w of Zn in 1 ml)
(BH4)2) (Preparation method is by W.J. Gensle
r,. F. JOhnsOn. A. D. B. SlOan,
．． J. Am. Chem. SOc. , ”ヱ,6074(
1960)) and stirred at room temperature for 5 hours. After the reaction, the mixture was poured into ice water containing 8 ml of AcOH, extracted with ether, washed with saturated NaI [CO3 aqueous solution and saturated brine, dried over anhydrous MgSO4, the solvent was distilled off, and the obtained oil was reconsolidated with ether-hexane. and (4) crystal 45
Get 4▼.

The mother liquor was subjected to silica gel column chromatography, and crystals 3 of (4) were obtained from the eluate of hexane:ethyl acetate (4:1 to 3:1).
28η is obtained. (Yield 454T19+328W-782
Wa, 55%) (4) 328m9 (0.696mmol
) in 2 ml of pyridine, 2 ml of acetic anhydride under ice-cooling,
Add 10 watts of 4-dimethylaminopyridine, return to room temperature, and stir for 1 hour. After the reaction, H20 was added, stirred at room temperature for 1 hour, excess acetic anhydride was decomposed, and extracted with ether.
% HCl aqueous solution, saturated NaHCO3 aqueous solution, and saturated brine, dried over anhydrous MgSO4, and the solvent was distilled off. When the obtained oil is recrystallized from ether, crystal 35 of (5) is obtained.
2η (yield 98%) is obtained. (5) 352 wa (0.6
85mm01) in 5ml of AcOHl, and add Zn powder 2
．． Add 00t and stir at room temperature for 2.5 hours.

Claims (1)

[Claims] 1. A sesquiterpene compound represented by the following structural formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼. 2 Structural formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ Processing of the compound represented by oxidizing agent Structural formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ Production of sesquiterpene compounds represented by Law.