JPS5855128B2 - Polyprenyl packaging materials - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a polyprenyl compound, and particularly to a method for selectively producing the trans isomer of a polyprenyl compound represented by the following formula: The above compound CI) is a novel compound that contains coenzyme Q and It is useful as an intermediate in the synthesis of substances active in living organisms such as vitamins, and is also useful as an intermediate in the synthesis of a compound known as gefarnate as a drug for treating ulcers.

The gist of the present invention is that the formula (II) [During the ceremony, R represents a lower alkyl group.

] A compound represented by the formula [■] [wherein R10R1 (R1 is a group used to protect a hydroxyl group such as acyl pyranyl) or a group that forms a carboxyl group, and the others are hydrogen atoms. ), X represents halogen (chlorine, bromine, etc.).

n is the same as above. ] is condensed to form the formula (
IV) [wherein R, R', and n are the same as above] A compound represented by the formula CI) is obtained by hydrolyzing and decarboxylating the obtained reaction product to obtain a compound represented by the formula CI) ζ. The invention consists in a method for producing a characteristic trans-type polyprenyl compound.

That is, the chemical transformation in the method of the present invention can be summarized by the following formula: [wherein R, R', R'', X and n are the same as above]
The condensation reaction between compound (n) and compound (I[[]) can be carried out, for example, using a basic catalyst (alkali metal, alkali This can be carried out by treatment at room temperature to reflux temperature in the presence of a metal hydride, alkali metal amide, alkali metal alkoxide, etc.).

Compound (IV) thus obtained can be hydrolyzed and decarboxylated by a conventional method, with or without separation from the reaction mixture, to obtain compound [■].

Here, hydrolysis is carried out, for example, by treatment with an alcoholic alkali (methanolic alkali hydroxide, ethanolic alkali hydroxide, etc.).

Decarboxylation is easily carried out by treating the hydrolyzate with hydrochloric acid, sulfuric acid, nitric acid, etc.

This decarboxylation is also 2/ of the moiety designated as -COOR in formula CIV).

When R' is -CH and becomes R3 after hydrolysis, -CH2-C0OH or CH(COO
H)2, which is decarboxylated only at high temperatures.

Purification and isolation of compound CI) is carried out using conventional separation means such as chromatography and molecular distillation.

Conventionally, various compounds having polyprenyl chains have been known, and many methods for producing them are also known.

However, since the polyprenyl chains present in biologically active substances have all trans-configurations derived from their double bonds, it is desirable to synthesize polyprenyl compounds with similar coordination, but conventional methods cannot produce polyprenyl chains. In addition to the trans isomer, the resulting reaction product usually contains a high proportion of the cis isomer.

Although there are methods to suppress the presence of cis isomers, such methods generally have poor yields, expensive reagents, and complicated operations, so they are not fully satisfactory industrially. There are some drawbacks that cannot be avoided.

On the other hand, polyprenyl compounds are found in plants (for example, phytol is found in chlorophyll in the form of an ester, and solanesol is found in tobacco leaves).

), so polyprenyl alcohol can also be obtained by extraction from these, but the number of carbon atoms in polyprenyl alcohol differs depending on the type of plant, the systematic relationship between them has not yet been clarified, and the extraction procedure is also complicated. There are many cases.

In addition, the types of naturally occurring polyprenyl compounds are
In terms of the number of carbon atoms, it has no choice but to be subject to restrictions that are comparable to those that are artificially synthesized.

The method of the present invention forms part of a synthetic route for stereospecifically producing polyprenyl compounds having various carbon numbers in good yield through simple chemical reaction operations, such as R=CH3, R ′-〇COCH3, R”=OH,
For the case where X=Br, the relationship between the present invention and its utilization route will be explained as follows: In the above, the method of the present invention relates to the first step and the second step.

Compound (I[), which is the starting material of the first step, has one prenyl chain added by passing through the third to seventh steps below.
It will be understood that a substance corresponding to can be obtained.

Here, as a result of the dehydration reaction in the fifth step, a new double bond is formed, but the group (-CH3) bonded to the tertiary carbon next to the carbon to which OH is bonded is the same. Therefore, no new geometric isomers will occur in this part.

Therefore, the initial starting material, i.e. the compound (III:n
By using a compound having trans coordination as =1), it is possible to easily produce a polyprenyl compound having trans coordination for all double bonds by carrying out the above method. The industrial significance is extremely significant.

Furthermore, in the oxidation reaction with selenium dioxide carried out in the sixth step, the fact that only the methyl group in the trans position is oxidized is disclosed in Japanese Patent Publication No. 1983-1973, published by the applicant and cited in the application.
As described in No. 884, this was confirmed entirely experimentally.

That is, when the compound produced in the fifth step is oxidized with selenium dioxide, one of the terminal methyls is first oxidized to alcohol,
As the reaction progresses further, it is oxidized to an aldehyde.

When this aldehyde was subjected to NMR analysis, it was found that δ9.
Since an aldehyde proton was observed at 31 (see column 5, line 14 of the above-mentioned publication), it was revealed that the methyl group at the trans position with respect to the long chain was oxidized (the aldehyde proton at the cis position was around δ10.11). It is expected that it will appear in

Regarding the cis-trans discrimination method using NMR spectra, please refer to the Journal of Organic
Chemistry33 9.3382 (1968)
reference).

Additionally, other researchers have confirmed that in the oxidation reaction of such compounds with selenium dioxide, the methyl group at the trans position is preferentially oxidized (
Journal of the America
nChemical 5ociety 93 A,
19.4835 (1971)).

In the compound CI) obtained by the method of the present invention, n=2
So, if R'' is -CH2-C00HO, leave it as is, -
CH(COOH)2 is converted to CH2-C0OH and becomes the raw material for an ulcer treatment drug called gefarnate.
See Index 9th Edition, 564 (1976) and Patent Application Publication No. 1983-5619].

The compound obtained by the dehydration reaction in the fifth step depends on the number of n, but there are many known ones, and this is used to obtain coenzyme Q by condensing it with 2,3-dimethoxy-5-methylhydroquinone. be done.

Next, the present invention will be specifically explained with reference to Examples.

Example 1 trans trans-3.7.11-trimethyl-2.
6 - Preparation of toticane-10-one-1-ol 1.92 of sodium hydride was suspended in 40 ml of ether, 5.21 of ethyl isobutyryl acetate was added under water cooling, and then trans-trans-1-bromo-8-acetoxy 8 g of -2,6-dimethyl-26-octadiene are added dropwise.

The reaction is carried out under reflux for 3 hours.

The ether layer is separated from the reaction mixture, washed with water, dried, and then the ether is distilled off to obtain an oily substance 9.91.

63 g of potassium hydroxide and 120 f of ethanol are added to this, and the mixture is refluxed for about 1 hour.

After adding the reaction mixture to ice water and acidifying with 10% sulfuric acid,
Extract with ether.

After washing the ether extract in the order of saturated brine, sodium bicarbonate solution, and water, the ether was distilled off to leave a residue 7.
Get 21.

This is dissolved in benzene and purified through a silica gel chromatography layer to obtain trans trans-3,7,11-trimethyl-2,6-dodecadiene 10-one-1-ol 6.2P.

N, M, R, (carbon tetrachloride) δ1.05 (d), 1.59 (s), 2.0 (s), 2
．． 1-2.7 (m), 3, 52 (s), 3.95 (d)
, 4.8-5.4 (m).

Example 2 trans trans-4・8・12-trimethyl-3・
Preparation of 7-dolidecadien-11-one-1,1-dicarboxylic acid 511 sodium metal was added to 760 ml of ethanol to prepare sodium alkoxide, and 481 ethyl isobutyryl acetate was added dropwise under water cooling.

After stirring for 30 minutes, diethyl trans,trans-4,8-dimethyl-3,7-nonadiene-9-from-1-dicarboxylate 751 is added dropwise and stirred for 8 hours.

After refluxing for an additional hour, the reaction mixture is poured into ice water and extracted with ether.

The ether extract was washed with water, the solvent was distilled off, and then distilled to give 8
Remove 90g of the fraction at 0°C/mmHg, add 46g of potassium hydroxide and 874ml of ethanol to the residue,
Reflux for 3 hours.

After adding the reaction mixture to ice water and acidifying with 10% sulfuric acid,
Extract with ether.

The ether extract was stirred with 10% carbonic acid solution), the aqueous layer was made acidic with acetic acid, and then extracted with ether again.

The ether extract was washed with water and dried to obtain 51 g of trans-trans-4,8,12-trimethyl-3,7-drylic acid-11-one-1-1 dicarboxylic acid.

1, R, 1710CrIl' (C=O), 2780~
2500CrIL' (COOH), 1670cIIl
(C=C).

Claims (1)

[Claims] A compound represented by formula 1 is condensed with a trans-form compound represented by the formula, and the resulting reaction product is hydrolyzed, treated with an acid, and decarboxylated to form a trans-form compound represented by the formula. A process for producing a trans-type polyprenyl compound, which is characterized by obtaining a compound [wherein R is a lower alkyl group, R' is 10R1 (R1 is a group used to protect a hydroxyl group) or a group that is decomposed to produce a carboxyl group. and the others are hydrogen atoms), "When R' is OR1, hydroxyl group, R'
represents a number. ].