JPS6135193B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides decahydro-
3a・6・6・9a-tetramethyl-(3aα・5aβ・
9aα・9bβ)-(±)-naphtho[2・1-b]furan-2(1H)one (common name, d・1-norambrenolide, hereinafter abbreviated as compound ())
Concerning the manufacturing method.

The above compound () has already been isolated and identified from cigars [H. Kaneko, Agr. Biol. Chem.,
35, 1461 (1971)], and is a compound known to impart a pleasant leafy aroma to tobacco as a tobacco flavor improver, and to exhibit the effect of suppressing irritation [US Pat. No. 2,905,576]. Compound () has 4 asymmetric carbon atoms and may exist in 8 types of stereoisomers, but the compounds shown in Compound () that exist naturally and are known to have an effect on improving tobacco flavor and taste. As shown in the figure, only the moieties forming each condensed ring exhibit a trans configuration.

Conventionally, the method for synthesizing compound () is to use sclareol as a starting material and oxidize it with chromic acid [L. Ruzicka, et.al, Helv.Chim.Acta,
14, 570 (1931)] is known as an industrial production method, but this method has the following problems: (1) Sclareol is expensive.

(2) Since sclareol is a natural product, the supply of raw materials is unstable.

(3) Since harmful chromic acid is used as a reaction reagent, there are environmental health problems.

There are drawbacks such as.

As a method to overcome the above-mentioned drawbacks, the present inventors have previously found that 4-methyl-6-
We have just filed a patent application for a method of synthesizing (2,6,6-trimethylcyclohexel)-hexenoic acid by acid-catalyzed cyclization [Japanese Patent Application Laid-Open No. 145869/1983].
In this synthetic method, the final cyclization reaction has a good yield and excellent stereoselectivity, but (1) in the previous step, 4-methyl-6-
(2,6,6-trimethylcyclohexenyl)-
The Wittig reaction used in the synthesis of hexenoic acid is a rather difficult process industrially.

(2) This reaction also has new drawbacks, such as the production of a large amount of triphenylphosphine oxide, an organic phosphorus compound, as a byproduct.

As a result of extensive research aimed at overcoming the drawbacks of the above two methods and developing a method for economically and industrially efficient production of the lactone represented by compound (), we found that Structural formula () easily derived from the synthesized alcohol shown in structural formula (), i.e., 3,7,11-trimethyldodeca-2,6,10-trienol [hereinafter abbreviated as compound ()], etc. Using the carboxylic acid shown in 4,8,12-trimethyltrideca-3,7,11-trienoic acid (hereinafter abbreviated as compound ()) as a starting material, compound () can be easily produced in good yield. We have discovered that it can be synthesized, and have accomplished the present invention.

That is, the gist of the present invention is to cyclize compound () using an acid catalyst to produce compound ().

The present invention will now be described in detail below. Compound (), which is the starting material of the present invention, is a known substance [G. Lucius, Chem. Ber., 93, 2663 (1960)], and can be easily derived from compound () etc. by a general method. That is, the compound () is made into a bromide by the action of phosphorus tribromide, then it is made into a cyanide by the action of sodium cyanide, and this is further dissolved in a 10% potassium hydroxide-methanol aqueous solution and refluxed to add water. By decomposition, the starting material compound () can be obtained in good yield.

First, compound () is dissolved in an organic solvent that does not solidify at low temperature, preferably dichloromethane, and then 0.1 to 100 equivalents, preferably 1
~10 equivalents of mineral acid or Lewis acid, preferably boron trifluoride ethyl ether, are added under cooling at 0°C to -78°C, preferably -20°C, for 1 to 120 minutes.
After preferably stirring for 20 to 60 minutes, the mixture is poured onto ice and extracted with an organic solvent, preferably ethyl ether, to obtain compound () in a yield of 30 to 50% based on the starting material, compound (). be able to. Compound () in the reaction product can be easily purified by operations such as chromatography, vacuum distillation, and crystallization.

The advantage of the present invention compared to conventional methods is that the starting compound () can be derived in a simpler process than an industrially inexpensive compound (), that is, the starting material can be obtained economically and stably. There is a certain point. In particular, the reaction process does not involve complicated operations such as the Wittig reaction and does not generate large amounts of organic phosphorus by-products, and is also excellent in terms of environmental hygiene.

Although the yield of the cyclization reaction is slightly lower than that of the conventional method, it is considered to have sufficient advantages as a whole, considering the ease of obtaining the above-mentioned starting materials. Since the cyclization reaction is also carried out under extremely mild conditions, the entire process is a synthetic method with extremely industrially advantageous characteristics.

Example 1 500 mg (2 mmol) of compound () was dissolved in 5 ml of dichloromethane and cooled to -18 to -20°C with ice salt. Add boron trifluoride ethyl ether to this solution.
After 576 mg (4 mmol) was added dropwise and reacted with stirring for 60 minutes, the reaction solution was poured onto ice and extracted with 100 ml of ether. The extracted ether layer was washed once with 5% aqueous sodium bicarbonate solution and three times with water, dried over magnesium sulfate, and then concentrated under reduced pressure to obtain 445 mg of product. After the product was purified by silica gel chromatography using a 9:1 mixed solvent of n-hexane and ethyl acetate,
Compound () was crystallized using n-hexane.
247 mg (yield 49%) was obtained.

The physicochemical data of the obtained compound () are as follows, and were completely consistent with the standard sample of compound ().

Mass spectrometry spectrum (70eV) m/e250 (M ⁺ ), 235, 207, 206, 137, 125,
124, 123, 109, 95, 82, 81, 69, 67, 55,
43, 41 Infrared absorption spectrum (cm ^-1 ) 1774, 1432, 1400, 1392, 1238, 1135, 1126,
1028, 959, 920 Nuclear magnetic resonance spectrum 0.84 (S, 3H), 0.88 (S, 3H), 0.91 (S,
3H), 1.33 (S, 3H), Example 2 5.0 g (20 mmol) of compound () was dissolved in 300 ml of acetonitrile and cooled to -18 to -20°C with ice salt. To this solution, 5.2 g (20 mmol) of stannic chloride was added dropwise and reacted with stirring for 20 minutes. The reaction solution was poured onto ice and extracted with 200 ml of ether. The extracted ether layer was washed once with a 5% aqueous sodium bicarbonate solution and three times with water, dried over magnesium sulfate, and then concentrated under reduced pressure to obtain 2.8 g of product. This product was purified by silica gel chromatography using a 9:1 mixed solvent of n-hexane and ethyl acetate, and then crystallized using n-hexane to obtain 1.65 g of compound () (yield 33%).
Obtained.

The physicochemical data of the obtained compound () were exactly the same as in Example 1, and completely matched with the standard sample of compound ().

Claims (1)

[Claims] 1 4,8,12-trimethyltrideca-3,7.
Decahydro-3a, 6, characterized by cyclizing 11-trienoic acid using an acid catalyst
6.9a-tetramethyl-(3aα・5aβ・9aα・9b
β)-(±)-naphtho[2.1-b]furan-2
Method for producing (1H)-one.