JPS5932471B2 - Sesquiterpene compounds and their production method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a compound of the general formula [wherein R represents -CH2OH, -CHO, or one D].

This invention relates to a novel sesquiterpene compound represented by the following formula 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 (
U? It is an important intermediate in the total synthesis of CinramOsmOlide) or CinramOsmOlide.

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
rm) 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 isodorimenine as a starting material, The present invention was completed in the process of total synthesis of cinnamodial or cinnamosmolide.

Compound 11ζ of the present invention is useful as an important intermediate in the next step in the total synthesis of cinnamodial or cinnamosmolide.

In the above step, the starting material 8-hydroxymethyl carbonate (1) is a novel compound synthesized for the first time by the present inventors, for example, isodrimenin (IsOdrimenin), which is isolated as a natural product.
) [J. Chem. SOc. , P. 4685 (1960
) can be obtained by the following steps. In addition,
The above-mentioned isodorimenine has already been completely synthesized by the present inventor as a sesquitel*<peno derivative derived from l-abietic acid, and 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)
-10n0ne) in an extremely short process (see Japanese Patent Publication No. 59-6313). To explain the steps for the total synthesis of cinnamodial or cinnamosmolide, the starting material 8-hydroxymethyl carbonate (1) is first converted into a trichloroethoxycarbonyl compound (
2), and then the non-containing compound (3). 6-hydroxy form (4), 6-acetoxy form (5), alcohol form (6
). Carboxylic acid (7), 6β hydroxylactone (8
) can be successively converted to synthesize cinnamosmolide (9).

Alternatively, the alcohol (6) may be converted into an aldehyde AI. Cinnamodial A4) can be synthesized by successive conversion into ketal AD, diol (alternative) and α-hydroxyaldehyde (auto). 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 is reacted with an oxidizing agent to obtain an enoone compound (3). The obtained engineering non-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. ．． 1
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 body (8) with an acetylating agent, cinnamosmolide 5
(9) can be obtained in high yield.

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

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

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

The obtained diol (substitute) 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 treating the 6-acetoxytrichloroethoxycarbonyl compound (5), which is the starting material of the present invention, with zinc powder in a solvent, the alcohol compound (6) is quantitatively obtained by removing trichloroethoxycarbonylation. As the solvent, alcohols and organic acids such as acetic acid can be used, and especially suitable results are obtained when acetic acid is used. Room temperature is sufficient for the reaction temperature, and a suitable reaction time is about 2 to 5 hours. When the obtained alcohol (6) is quickly reacted with an oxidizing agent, aldehyde (self) can be obtained in high yield.

The oxidant used in this oxidation reaction is John's (JO
nes) reagent is preferably used, and acetone is particularly effectively used as a solvent.The reaction temperature and reaction time are not particularly limited, but the reaction can be carried out at approximately 0 to 0°C and in a short time of about 30 minutes. proceed. By treating the obtained aldehyde (auto) with a dialcohol and an organic acid to further protect it with an acetal, a ketal AO safe to alkali can be obtained. In this case, organic acids such as p-toluenesulfonic acid and Ganfersulfonic acid are used, aromatic hydrocarbons such as benzene and toluene are used as solvents, and as dialcohols, ethylene glycol, 1,3-propanediol etc. can be used, especially in benzene solution, p-toluenesulfonic acid, 1
- It is preferable to use 3-propanediol.

The reaction temperature and reaction time at this time are not particularly limited, but
Each reacts well at about 80 to 150°C and in a short time of about 1 hour.

The present invention will be explained below using reference examples and examples.

In addition, compounds (2), (3), (4), (5), aω,
All ADs are new compounds. [Reference example 1 (1) 280~(1.00mm01) to ether 10
ml, add 2 ml of pyridine, and add β, β,
β-trichloroethoxycarbonyl chloride 268μ
1 (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 at step 4, the solvent was distilled off, and the residue was subjected to silica gel column chromatography to obtain 439m9 of crystals of (2) (96% yield) from the hexane-ethyl acetate (3:1) eluate. [(2
) Physical properties of M. p. : 121-122℃ (from ether to plate crystal) Elemental analysis: ER (CHCl3): 1790, 1760a'-
1NMR (100MHz, CDCl3): Reference example 2 (2) 228m9 (0.500mm01) of AcOH
Dissolve in 5ml of CrO325Om9 (2.50mm
01) and stirred 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 gives 192Tn9 as an oil. This was subjected to silica gel column chromatography, and 150~(64% yield) of (3) was obtained from the hexane-ethyl acetate (5:1~3:1) eluate. (3) 1409η(3
．． OOmmo1) was suspended in 60 ml of anhydrous ether, and Z
n(BH4)2 ether solution (34 ~ Zn in 1 ml)
BH4)2) (preparation method is by W.J. Gensler)
．． F. Johnson,. A,D. B. S10an,.
J. Am. Chem. Soc. , foot, 6074 (1
960)) and stirred at room temperature for 5 hours.
After the reaction, it was poured into ice water containing 8 ml of AcOH, extracted with ether, washed with saturated aqueous NaHCO3 solution and saturated brine, dried over anhydrous MgSO4, the solvent was distilled off, and the resulting oil was reconsolidated with ether-hexane. (4) crystal 454η
get. The mother liquor was subjected to silica gel column chromatography, and from the eluate of hexane:ethyl acetate (4:1 to 3:1) (4)
A crystal of 328η is obtained. (Yield 454Tr9+328T
rl9=782m9, 55%) (4) 328wvi7
(0.696 mm01) was dissolved in 2 mι of pyridine, and under ice-cooling, 2 m1 of acetic anhydride and 10 ml of 4-dimethylaminopyridine were added.
Add ~, return to room temperature, and stir for 1 hour.

After the reaction, add H2O, stir at room temperature for 1 hour, decompose excess acetic anhydride, and extract with ether. H2O, 5% HCI aqueous solution,
Saturated NaHCO3 aqueous solution, washed with saturated saline, anhydrous Mg
Dry with SO4 and evaporate the solvent. The obtained oil was recrystallized from ether to give crystals 352~ (yield 98%) of (5).
). [Physical properties of (5)] M. p. : 146-149℃ (ether to needle crystals)
Elemental analysis: Example 1 (5) 352~(0.685mm01) in AcOHl
Dissolve in 5ml, add Zn powder 2.00V, and incubate at room temperature for 2.
Stir for 5 hours.

The precipitate formed after the reaction was dissolved by adding H2O, and the unreacted Z
Separate n. The filtrate was extracted with ether, H2O, saturated N
aHCO3 aqueous solution, washed with saturated saline, anhydrous MgSO.
When the solvent is distilled off, oily product 247 is obtained. This was subjected to silica gel column chromatography, and hexane:
Crystals 195 of (6) were obtained from the eluate of ethyl acetate (1:1).
η (yield 84%) is obtained. [Physical properties of (6)] (6) 676Tr! 9 (2.00 mm 01) in 30 ml of acetone and stirred under ice cooling.
s) Test> Add 1.0ml of the drug dropwise over 30 minutes, immediately add H2O and extract with ether.
The mixture is washed with an aqueous O3 solution and saturated brine, dried over anhydrous MgSO4, the solvent is distilled off, and the resulting oil is recrystallized from ether to obtain crystals of AO) 455jη.

Claims (1)

[Claims] 1. General formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [However, in the formula, R represents -CH_2OH, -CHO, ▲There are mathematical formulas, chemical formulas, tables, etc.▼. ] A sesquiterpene compound represented by 2. The compound according to claim 1, wherein R is -CH_2OH. 3. The compound according to claim 1, wherein R is -CHO. 4. The compound according to claim 1, wherein R is ▲a numerical formula, a chemical formula, a table, etc.▼. 5 Structural formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Structural formula characterized by treating the compound represented by dialcohol and organic acid: ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Sesquiterpene compound manufacturing method. 6 Structural formula: ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Treated with an oxidizing agent to obtain a compound represented by the structural formula: ▲ Numerical formulas, chemical formulas, tables, etc. A method for producing a sesquiterpene compound represented by the structural formula: ▲Mathematical formula, chemical formula, table, etc.▼ characterized by treatment with alcohol and organic acid. 7 Structural formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ Treated with zinc powder to obtain a compound represented by structural formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼, and the compound was oxidized. Structural formula: ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Structural formula characterized by treating the compound with a dialcohol and an organic acid: ▲ Numerical formulas, chemical formulas, tables, etc. A method for producing sesquiterpene compounds represented by ▼.