JPS58144343A - Polyprenyl acetone - Google Patents

Abstract

NEW MATERIAL:Polyprenyl acetone of formulaI(formula II is trans isoprene unit; formula III represents cis isoprene unit; n is integer of 11-19). USE:A raw material of drugs and cosmetics: especially it is a synthetic intermediate of mammarian dolichols having very important roles on maintaining life of living bodies. PREPARATION:The reaction of a polyprenyl halide of formula IV (X is halogen) with an acetoacetic ester of CH3COCH2COOR (R is lower alkyl) is carried out in the presence of a base such as sodium hydride to give a polyprenylketocarboxylic ester of formula V. Then, the product is subjected to known saponification and decarboxylation to give the compound of formulaI. The mammarian dolichol of formula VI (j is n) can be synthesized from the product.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to polyprenylacetone. More specifically, the present invention is based on the general formula 0 (wherein -CH2-C=C-CH2- represents a single CM position of trans-inoprene, and -CH2- and -CH5- represent a sila type Yipple.

It represents a unit, and n is an integer from 11 to 19. ) is related to a novel polyprenylacetone.

The polyprenylacetone represented by the general formula (1) provided by the present invention is a substance useful as a raw material for medicines, cosmetics, etc., and is particularly useful as a synthetic intermediate for mammalian dolichols.

Dolichols were first isolated from pig liver in 1960 by J. F. Pennock et al.
e (London).

186.470 (1960)], which was later changed to the general formula (A) Unit 1 Table ゎ2, -CHz-6=6-CH2-tit,
A mixture of polyprenol analogues having the structure shown in It was revealed that the value of j is generally distributed from 12 to 18, and three homologs of j=x4.ts and 16 are the main constituents (R, W).

Keenan et al., Biochemica
l Journal, 165, 505□,
□ (Refer to 1977'l).Dolichols are widely distributed not only in the liver of pigs but also in the bodies of mammals, and are known to play extremely important functions in maintaining the life of living organisms.For example, , J.B., Harford et al. have shown that exogenous dolichol promotes the incorporation of sugar components such as mannose into lipids, and as a result, has the effect of increasing the formation of glycoproteins, which are important for sustaining the life of living organisms. (Biochemical and Bi
Physical Research Community
cation, 76, 1036 (1977).The effect of adolichols on promoting the incorporation of sugar components into lipids is more pronounced in already mature animals than in living organisms during the growing stage; The functions of dolichols are attracting attention.

In addition, R, W., and Keenan et al. stated that it is important for rapidly growing organisms, such as those in childhood, to ingest dolichol from outside and supplement the dolichol obtained by biosynthesis within the body. (Archiveso
fBlochemistry and Biophy
sics, 179, 634 (1977)].

Furthermore, we quantified dolichol phosphate ester in the regenerated livers of Akamatsu et al. found that the function was improved by adding dolichol phosphate from the outside [No. 54]
Presented at the Japanese Biochemical Society Convention (1981)].

As mentioned above, dolichols are substances that control extremely important functions for living organisms, and are useful as pharmaceuticals or their intermediates. Finally 0.6
You can only get the doli call of F (F, W, B
Urgos et al.
Journal, 88, 470 (1963)]. It is extremely difficult to completely synthesize dolichols using current organic synthesis techniques, as evidenced by their complex and unique molecular structures. Relying on natural products for synthetic intermediates,
If it were possible to obtain dolichols by simply adding a simple synthetic chemical treatment to them, it would be Cloth Piece 1j, but such a convenient substance has not been found so far. Conventionally, the following general formula (B)
) [however, k = 4 to 6]
It is known that becprenols (these are called vecprenols) can be collected from Betula verrucola; It is almost impossible to synthesize the main dolichols using current organic synthesis technology. K again.

Hannus et al.
reported that a polyprenyl component was isolated from leaves of D. vestris at a yield of 1- on a dry weight basis, and that this component was a polyprenyl acetate mixture having 10 to 19 imprene units mainly in the cis configuration. (
Phytochemigtry, 13, 2563
(1974)], the details of the trans and cis configurations in #ia polyprenyl acetate have not been elucidated in their report. Furthermore, D, F, Zinc
kel et al. strobe pine (Pinus 5trobus)
It has been reported that C90 polyprenol having 18 inprene units or an average value of 18 inbrey units exists in the extract of leaves of Phytoc.
Hemistry, 11, 3387 (1972)]; this report does not provide a detailed analysis of the trans and cis configurations of the polyprenol.

Some of the present inventors and their co-researchers first hydrolyzed extracts extracted from ginkgo biloba and Himalayan cedar using organic solvents, if necessary, and then performed chromatography, fractional dissolution, or other suitable separation methods. a polyprenyl fraction consisting of a polyprenol and/or a mixture of its acetate homologues having 14 to 22 isoprene units in the trans, cis configuration exactly as mammalian dolichols is obtained, that the fraction exhibits a distribution of polyprenyl congeners very similar to the distribution of polyprenyl congeners in mammalian dolichols, with the only absence of alpha-terminal saturated isoprene units compared to mammalian dolichols; If desired, the polyprenyl fraction can be relatively easily separated into its constituent individual polyprenyl homologues (with a uniform number of inoprene units), and therefore the polyprenyl fraction is also very useful as an intermediate for the synthesis of mammalian dolichols. I found it suitable.

In order to efficiently produce mammalian dolichols using the above-mentioned polyprenyl compounds, the present inventors have intensively investigated a method of introducing a saturated inobrene unit into the α-terminus of the polyprenyl chain of the polyprenyl compound, and have found that such a method The present invention was completed by creating polyprenylacetone represented by the general formula (1), which is useful as an intermediate in the following.

Polyprenylacetone of the present invention represented by general formula (1) [hereinafter referred to as polyprenylacetone CI]. ] is a polyprenylno-ride (hereinafter referred to as polyprenylno-ride (II)) represented by the general formula (wherein X represents a halogen atom and n is as defined above). ] in the presence of a basic compound to form an acetoacetate represented by the general formula (wherein R represents a lower alkyl group) [hereinafter referred to as acetoacetate (I). ] [hereinafter referred to as polyprenylketocarboxylic acid] It can be obtained by saponifying and decarboxylating an ester (denoted as 0)].

As mentioned above, polyprenyl I-ride (II) is a polyprenol represented by the general formula (wherein n is as defined above) that can be obtained directly or through hydrolysis from extracts of Japanese koji or Himalayan cedar, or It can be easily obtained by halogenating the mixture with a chemical agent such as trihalogenide such as PCl5 or PBrs, or thionyllide such as SOα2.5OBrt. This halogenation reaction is usually carried out by dissolving the polyprenol in a suitable solvent such as hexane or diethyl ether, and adding triethylamine,
This is carried out by adding a halogenating agent at a temperature of about -20°C to +5'θ°C in the presence or absence of a base such as pyridine.

The reaction between polyprenylno-ride (II) and acetoacetate (■) is preferably carried out in a solvent.

Suitable solvents include ether solvents such as diethyl ether, tetrahydrofuran, dioxane, and dimethoxyethane. The amount of solvent used is not critical, but is
~100 times (by weight), preferably 5 to 80 times (by weight),
More preferably 10 to 50 times (weight). It is preferable to use a sufficiently dried solvent for the purpose of the reaction to proceed smoothly. In order to carry out this reaction, it is necessary to have a basic compound present. Essential.The basic compounds used include sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, sodium t-
Preferred are alkali metal hydrides, hydroxides, or alkoxides such as butoxide, potassium 1-butoxide, sodium methoxide, and sodium ethoxide, or n-butyllithium, methyllithium, and the like. The basic compound is generally about 0.1 to 5.0 mol, preferably 0.5 to 3.0 mol, more preferably 7 to 1.5 mol per mol of acetoacetate (■). Used in percentages. In a preferred embodiment, acetoacetate ([
[l) or conversely, acetoacetate (ff
By gradually adding the basic compound all at once or little by little to the solution of [), the anion of acetoacetate is first formed, and then polyprenyl halide (n) is added thereto for reaction.

Acetoacetate (In) and polydalenyl halide (
The proportion of acetoacetate (II[)/polyprenyl halide (It) is not critical;
molar ratio of 1/2 to 20/1, preferably 415 to
10/1. More preferably, it is 1/1 to 5/1. When forming the anion of acetoacetate (III), under an inert gas atmosphere such as nitrogen gas or argon.
It is desirable to carry out the reaction at a temperature of 30°C to +100°C, preferably -10°C to +80°C, whereby the desired anion can be smoothly formed while suppressing side reactions. The time required for this anion formation varies depending on the reaction temperature used, but usually about 10 minutes to 5 hours is sufficient.

be. Acetoacetate ester thus prepared (
Polyprenylno-rad (n) is added to the anion solution of [) and reacted. Depending on the reaction conditions used, the reaction may proceed smoothly by adding polyprenyl halide (II) in small portions or in a dropwise manner rather than adding the entire amount at once. The temperature within the reaction system during the addition of polyprenyl halide (1) and afterward until the reaction is completed is not critical, but is preferably within the range of -10°C to the boiling point of the solvent used. . If the reaction temperature is too low, the reaction progresses slowly and it takes too much time to complete one reaction.

On the other hand, if the reaction temperature is too high, undesirable side reactions will proceed. From this point of view, it is preferable to employ a reaction temperature within the range of 0°C to 80°C. Polyprenyl halide (In
In order to complete the reaction after adding , it is necessary to continue stirring the reaction mixture at the above reaction temperature, and the time required for this varies depending on the reaction temperature used, but is usually about 30 minutes to 24 hours. . In order to confirm the progress of the reaction, it is convenient and preferable to monitor the decrease in the raw material polyprenyl halide (It) by thin layer chromatography.

After the reaction, isolation of the polyprenylketocarboxylic acid ester <-W) from the reaction mixture can be easily accomplished by applying isolation methods conventionally used in known synthetic reactions. In particular, chromatography is conveniently used. Adsorbents that can be used in chromatography include silica gel, alumina, activated carbon, and cellulose. Among these, silica gel is particularly preferably used. As a developing solvent, a mixture of a small amount of a polar solvent such as diethyl ether, chloroform, ethyl acetate, or ethyl alcohol with a hydrocarbon solvent such as hexane, pentane, petroleum ether, or benzene is suitable.

It is also possible to omit this isolation step and directly perform the synthesis reaction of polyprenylacetate/(I) in the next step, followed by the purification step. can be saponified by applying the method used for the saponification reaction of higher fatty acid esters. For example, the objective can be achieved by stirring polyprenylketocarboxylic acid ester (■) with sodium hydroxide or potassium hydroxide in aqueous methanol, aqueous ethanol or aqueous inoglobanol. The amount of sodium hydroxide or potassium hydroxide used is about 1.0 to 20.0 molar equivalents, preferably 1.5 to 10.0 molar equivalents, relative to polyprenylketocarboxylic acid ester (IV). desirable.

Hydrous alcohols such as those mentioned above are suitable as the reaction solvent, but polyprenylketocarboxylic acid ester (fV
It is also preferable to add a small amount of a hydrocarbon solvent such as hexane, pentane, benzene, toluene, etc. in order to improve the solubility of '). In order to make the saponification reaction proceed smoothly, 1
The reaction temperature is preferably from 0°C to the boiling point of the solvent used, preferably from 25 to 65°C. The time required to complete the reaction varies depending on the temperature conditions employed at this time, but is usually within a range of about 0.5 to 24 hours.

After carrying out the saponification reaction as described above, preferably t
If the reaction solution is neutralized using a mineral acid such as hydrochloric acid or sulfuric acid under room temperature conditions or ice-cooled conditions, and then the reaction solution is made into acidic conditions of about 1 to 3 degrees, a decarboxylation reaction will occur automatically. 5 Polyprenylacetone (1), a compound of the present invention, is formed. After the decarboxylation reaction is completed, the reaction solution is extracted with hexane, benzene, diethyl ether, etc., washed thoroughly with water, the organic layer is dried, and the solvent is distilled off to obtain a crude product of the target compound polyprenylacetone (1). can get. In order to purify this product, a chromatography method is preferably employed. Adsorbents used in the chromatography method include silica gel, alumina, activated carbon, and cellulose, with silica gel being particularly preferred. As the developing solvent, a mixture of a small amount of a polar solvent such as diethyl ether, diimpropyl ether, chloroform, ethyl acetate, methyl acetate, etc. with a hydrocarbon solvent such as hexane, pentane, petroleum ether, benzene, or toluene is suitable.

Polyprenylacetate synthesized by the above method) 7
(1) is a new compound that has not been described in any literature, and is particularly useful as a raw material for the synthesis of mammalian dolichols. Mammalian dolichols can be synthesized from this compound, for example, by the synthetic route shown below.

(1”) (■) (■) (■) However, in the above formula, the radical represents a group represented by the formula (in the formula, n is as defined above), and R' represents a lower alkyl group. In (2), polyprenylacetone (1) t-1 is subjected to a WitLig reaction using any reagent to obtain polyprenylcarboxylic acid ester (Vi), followed by hydrolysis of the polyprenylcarbon modified ester CVI), The isoprene unit portion at the α-terminus is selectively hydrogenated (reaction ■) in the presence of a palladium, nickel or rhodium-based catalyst, and the polyprenylcarboxylic acid (■) having a saturated isoprene unit at the resulting α-terminal 4 portion is For example, alcohol (■
), that is, mammalian dolichols can be synthesized.

Hereinafter, the present invention will be explained in more detail with reference to Examples and Reference Examples. In addition, IR analysis in Examples and Reference Examples was measured using a liquid film, and NMR analysis was measured using TMS as an internal standard. FD-MASS analysis value rjIH, 12C, 16
(), Mα, corrected LfC value r6 as 79f3r
Ru.

Reference example 1 Separation of polypresol Ginkgo biloba s, 10 kami (
After drying with hot air at about 40°C for 24 hours, the sample was extracted by immersing it in chloroform 8041 at room temperature (about 15°C). Petroleum ether 5I was added to the concentrate obtained by distilling off chloroform from this extract to separate insoluble components, and the F solution was separated using a silica gel column using reduced diameter chloroform as a developing solvent to form an oil of about 37F. I got something.

Approximately 400 wtl of acetate was added to this oil to dissolve the acetone-soluble components, the resulting mixture was mixed, the F solution was concentrated, and the resulting oil was dissolved in methanol (4QQau).

Wed 4Qyn! After heating at 65°C for 2 hours with 20f of sodium hydroxide, methanol was distilled off, and the residue was extracted with diethyl ether (5ootg). Drying over sodium and evaporation of the solvent gave 24.29 as an oil.

Next, this oily substance was separated using a mixture of n-hexane/isopropyl ether=90/10 (volume ratio) using about 1 mm of silica gel to obtain a 21.8F oily substance. This oil is a polyprenol with a purity of more than 95%,
About this product: Merck semi-preparative high performance liquid chromatography column LiChrosorb RP18-10 (C1”
type) using acetone/methanol =, 90/10 (
High performance liquid chromatography analysis was performed using a mixed solvent (volume ratio) as the eluent and a differential refractometer as the detector.
The results of determining the area ratio of each peak in the obtained Chromadog2m were as follows.

1 11 0.32
12 1.13 13
5.94 14
25.65 15 39.4
6 16 19.27
17 5.98 18
1.89 19 0.
8 Using this high-performance liquid chromatography, separate each component from the above oily substance, perform mass spectrometry, infrared absorption spectrum, IH-NMR spectrum and I3C-NM.
It was confirmed by R Subekator that these components were polyprenol having a structure represented by general formula (V).

Field ionization mass spectrometry (FD-MASS) for each component
) results and IH-NMR δ values are shown in Table IK, "('
-NMR δ values are summarized in Table 2. Polyprenol 12.4F of general formula (■) with 0n = 15 and pyridine 11 were added to 200 IIE/n-hexane, and the resulting solution was added to room temperature ( 2.Of phosphorus tribromide was added dropwise under a nitrogen gas atmosphere at approximately 20"C). After the addition was completed, the solution was stirred overnight at the mold temperature under a nitrogen gas atmosphere.Then, this n-hexane solution was placed in a separatory funnel. , 3@ with about 5011Ll of water
After washing, drying with anhydrous magnesium sulfate and distilling off n-hexane, a particularly pale yellow liquid was obtained12. I got Of.

When NMR analysis was performed on this product, it was found that the signal (d, δ, = 4.08) attributed to the -C2GE (group) of the raw material polyprenol disappeared and a new -CH2Br
Kl) An IM signal (d, δ=-3,91) appeared. In '1, the octopus liquid was analyzed by FD-MASS and found to be m/e=1304. These analysis results confirmed that the above product was a polyprenyl bromide with the general formula (I[)VC, where H=15 and A==Br.

Through similar operations, polyprenyl chlorides with n other than 15 and polyprenyl bromide mixtures with n arbitrarily distributed between 11 and 19 were also synthesized.

Reference Example 3 Synthesis of polyprenyl chloride Polyprenol 12.4F of the general formula (IV) where n = 15 and 1.0 ml of pyridine were added to 200 w1 (On-hexane), and the resulting solution was placed in a room under a nitrogen gas atmosphere. Add 1.5 F of thionyl chloride dropwise at the source, and after the completion of the drop, add 2 more at room temperature.
Stir for hours. This reaction mixture was then post-treated in the same manner as in Reference Example 2 to obtain pale yellow liquid 11.2F. When this product was subjected to IR analysis, it was found that the absorption caused by the OH groups of the raw material polyprenol had disappeared.

In addition, when NMR analysis was performed, the signal assigned to -Ctan20H of the raw material polyprenol disappeared, and a new signal assigned to -Ctan2C1 (d, δ = 3.95
) appeared. In addition, by FD-, MASS analysis, m
/e2 gave 1260 ft. From the above, the above product has the general formula (l
[) It was confirmed that it was polyprenyl chloride.

Polyprenyl chlorides having pn other than 15 and polyprenyl chloride mixtures having pn arbitrarily distributed between 11 and 190 were also synthesized by similar operations.

Example 1 A three-necked flask was charged with 3°d of anhydrous tetrahydrofuran and 640"P of sodium 50 thihydride, and 1.57 t of ethyl acetoacetate was added dropwise to the flask while stirring at room temperature. The intense hydrogen gas evolution gradually subsided. Afterwards, the temperature was gradually raised while purging the inside of the flask with nitrogen gas, and stirring was continued for 1 hour under refluxing conditions of the solvent.Then, the reaction system was cooled to room temperature, and the general formula synthesized according to Reference Example 2 (
Tetrahuman a7 of polyprenyl bromide 4.30f with n = l 5 and X = Br in It')
C1(1/) solution was added dropwise and stirred at room temperature overnight. After the solvent was distilled off from the reaction mixture using a rotary evaporator, the residue was poured into about 20 g of water and extracted with diethyl ether. The mixture was then washed, dried over anhydrous magnesium sulfate, and diethyl ether was distilled off using a rotary evaporator to obtain a yellow liquid.

This yellow liquid was heated to 1 mHftc for 30 minutes at 150°C.
The low-boiling components were distilled off by heating for a minute, and the residue was subjected to silica gel column chromatography [hexane/ethyl acetate = 98.
/2 (volume ratio) with the developing solution] to obtain a pale yellow liquid 2.48F. The analysis results of this product are shown below.

IR analysis: 1740, 1715, 1660.830m
-”IH-NMR analysis: δg=, , 1-21 (3H
*tsco2cn2Cdan3).

3.21 (IJ t*””’Anus 33 zHs”4.11
(2H, q, -CO2Cdan2CHs) FD-MAS
S analysis: According to the analysis result of m/e = 1354 or more, this slightly yellow liquid substance has the general formula (IV) K = 15
, was confirmed to be ethyl polyprenylketocarboxylate in which R=C2H8.

This polyprenyl ketocarboxylic acid ether was then added to a solution of 0.5 ys of sodium hydroxide, 2 Qtxl of ethanol, and 51 liters of water, and after stirring for 3 hours under reflux, most of the ethanol was distilled off using a rotary evaporator. left,
The residue was poured into about 20 m of ice, concentrated hydrochloric acid was added little by little to make it acidic to about 2, and then extracted with hexane. The hexane layer was thoroughly washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off to obtain a yellow viscous liquid. This material was subjected to silica gel column chromatography [
Hexane/ethyl acetate = 98/2 (volume ratio) was used as a developing solution] to obtain a slightly yellow viscous liquid with a volume of 1.98
I got f. The analysis results of this product are shown below.
, 1.62 (s, 48H).

Cα4 1.7-2.4 (m, 75H), 5.05 (br,
18H) FD-MA158 analysis 2m/e=xzsz From the analysis results above, it was confirmed that this slightly yellow liquid was polyprenylacetone in which n=15 in general formula (1). ...General formula (II) is obtained by similar operation.
From each polyprenyl bromide in which n is a value other than 15 between 11 and 190, each polyprenyl in which n is 11°12.13, 14, 16, 17.18 and 19 in the corresponding general formula (1) Synthesized acetone. Their yields were approximately the same as those obtained when polyprenylacetone with n=15 was synthesized. Further, the characteristic absorption of their infrared absorption spectrum and the characteristic signal of their IHNMR spectrum coincided with those of the above polyprenylacetone with n=15 at that position.

Example 2 Methyl acetoacetate instead of ethyl acetoacetate 1.40$
' was reacted with polyprenyl bromide and purified in the same manner as in Example 1, resulting in a pale yellow liquid 2.2.
I got 62. NMR analysis, IR analysis and F
D-MASS analysis gave the following results,
In this case, n=15 in the general formula (to). R=CHs
It was confirmed that it was methyl polyprenylketocarboxylate.

IR analysis: 1740, 1720, 1660.830m
"IH-NMR analysis: δpprn Cα4 3.78 (3H, a, -CO snow CHs) FD-MA88
Analysis: m/e=ta+.

This methyl polyprenylketocarboxylate was saponified, decarboxylated and purified according to the method of Example 1 to obtain a slightly yellow liquid having a concentration of 1.87F. The IR, IH-NMR and FD-MA8S analysis results of this product were the same as those obtained for the polyprenylacetone of Example 1. (Voluntary initiative) May 1980, Commissioner of the Japan Patent Office Haruki Shimada1, Indication of the case 1982 Patent Application No. 265002, Name of the invention Polyprenylacetone (108) Rira Co., Ltd. Representative Tsuguo Shioka Hayashi4, Agent telephone Tokyo 03 (277) 3182 6 Contents of correction (1) ``(approximately 15℃
) and insert ``1 henma'' between ``chloroform'' and ``chloroform''.

(2) rA-BrJ in the 5th line from the bottom of page 24 of the specification
Change it to X = Br J.

(3) Change “Mu=C1” in the 5th line from the bottom of page 25 of the specification to “
Changed to ``X 冨σ''.

(4) On page 29 of the specification letter @ line B, after "Agreed.""Furthermore, the results of the FD-MA88 analysis of these polyprenylacetones were as follows.

1 1 101
012 10781
5 11461
4 12141
6 13501
7 14181
8 14861
9 1554
join.

(5) “It was the same as that” on page 30, line 9 of the specification.

'', the following Example 3 is added.

"Example 3 In the general formula (7) obtained in the same manner as Reference Example 1, n
is distributed from 11 to 19 and whose composition is substantially the same as that described in Reference Example 1, is reacted with tooled phosphorus according to the method of Reference Example 2 to obtain a polyprenyl bromide mixture, 509 was reacted with ethyl acetoacetate in the same manner as in Example 1 to produce ethyl polyprenylketocarboxylate.
After saponification and decarboxylation in the same manner as above, a slightly yellow viscous liquid-2 was obtained by separating and purifying the product.

The IR, E-NMR analysis results of this product were found to be substantially the same as those obtained for the polyprenylacetone of Example 1 in terms of characteristic absorption and position of characteristic signals.

” Procedural amendment (spontaneous) 1981 (Ko 18th) Mr. Kazuo Wakasugi, Commissioner of the Japan Patent Office1, Indication of the case 1982 Patent Application No. 263002, Name of the invention polyprenylacetate/3, Person making the amendment Case and Relationship between patent applicant: 1621 Sakazu, Kurashiki City (10B') RiRa Co., Ltd. Ueno et al. 4, agent 5, subject of amendment 6, detailed description of the invention in the statement of contents of the amendment End (May 11, 1982)
The following Reference Example 4 is added to the end of Example 3 (which was added to page 30 of the specification) by the written amendment submitted on the day of the application.

"Reference Example 4 Anhydrous tetrahydrone run 40- and 5
Add 220"f of 0% sodium hydride, stir at room temperature, and add diethylphosphonoacetate ether [(CtHs+O
) Goose J'CHtCO嘗C*Hs) 1. Of 10W
A solution of Ll dissolved in anhydrous tetrahydro7rane was added dropwise. After completion of the addition, stirring was continued for an additional hour at room temperature.
A solution of 1.92f of polyprenylacetone, which is n-15 in the general formula (1) synthesized in Example 1, dissolved in 1Qsu of anhydrous tetrahydrone was added dropwise at room temperature, and after completion of the addition, the solution was added dropwise to *ii for 30 minutes, 50~ The mixture was further stirred at 60°C for 3 hours. Then, after cooling to room temperature and adding about 1 d of water, the solvent was distilled off using a rotary evaporator, and the residue had a volume of about 50 wLl.
of water was added and extracted with hexane. The hexane layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the hexane was distilled off to obtain a yellow liquid. This liquid was purified by silica gel column chromatography (hexane/ethyl acetate = 9872 volume ratio was used as the developing solution).
．． A colorless liquid of 62F was obtained. According to the analysis results below, in the above formula (■), n = i s s R'-
It was confirmed to be ethyl polyprenylcarboxylate, which is C*Hs.

IR analysis: 1715, 1640, 1440, 1385,
1210°1135.830,790eM' pm IH-NMR analysis: δ 1.20 (t, 3H
), 1.53 (8,9H).

Cα4 1.62 (S, 48H), 1.7-2.4 (
m, 75H).

4.06 (Q*2H), 5.06 (br, 18H), &
56 (br, IH) FD-MASS analysis: m/e=13
52 Then the above polyprenylcarboxylic acid ethyl 1.62
f was added to a solution of 0.3 f of sodium hydroxide, 3 wg of water, and 20 M of ethanol, and after stirring under reflux conditions for 5 hours, most of the ethanol was distilled off using a rotary evaporator.
101 LLl of water was added, the pH was adjusted to about 5 with diluted hydrochloric acid, and the mixture was extracted with hexane. The hexane layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off to obtain a yellow liquid. This product was purified by silica gel column chromatography [hexane/ethyl acetate-90/10 (volume ratio) was used as a developing solution] to obtain a colorless liquid of 1.42F. According to the following analytical results, this product has n''
It was confirmed that it was a polyprenylcarboxylic acid with a formula of 15.

IR analysis t 3600-290G (weak).

2800-2400 (w axis k).

1690.1660, 1630t1440, 1375.
830 m-1 pm IH-NMR analysis (δ) I Cα4 1.53 (8,9H), 1i62 (S, 4814).

1.7-2.4 (m, 75H), 5.06 (
br, 18H).

5.56 (br, ] IHs~11.5 (br
, IH).

Next, this polyprenylcarbo7rM1.421 was selectively hydrogenated by the method shown below to obtain 0μ.

μ′-dichlorobis(1,5-cyclooctadiene)rhodium(1) 0.7119 and neomenthyldiphenylphosphine 7,3”P were placed in a pressure bottle and degassed while stirring with a magnetic stirrer. The atmosphere was purged with argon, 5 wl of distilled absolute ethanol was added, and the resulting yellow solution was stirred for 30 minutes under a hydrogen pressure of 3 atm.

Separately, a solution of 1.42F polyprenylcarboxylic acid and 17"lt of sodium methoxide dissolved in 4d of absolute ethanol was stirred under an argon atmosphere.The catalyst solution and polyprenylcarboxylic acid solution prepared in this way were The autoclave was previously degassed and replaced with argon, and the autoclave was transferred through an exhaust pipe, and a hydrogen pressure of 2.5 atm was applied to carry out a hydrogenation reaction at the mold temperature for 24 hours.The solution after the reaction was collected using a rotary evaporator. Diluted hydrochloric acid was added to the residue, extracted with hexane, dried over magnesium sulfate, and the solvent was distilled off to obtain a yellow liquid-free substance 1.402. This was subjected to silica gel column chromatography [hexane/ Using ethyl acetate = 90:10 (volume ratio) as a developing solution], a colorless viscous liquid 1.25F was obtained.
It was confirmed that it was a dihydropolyprenylcarboxylic acid with a formula of 15.

IR analysis: 3600-2900 (Weak).

2800-2400 (weak).

1705.1660,1440,1375,830-
11H-NMR analysis (Jgg":>: 1.53 (8,9H), 1.62 (S, 48H).

1.7-2-5 (m, 76H), 5.06 (
br, 18H).

~I Q, 0 (br, IH) [δ5 present in the raw material unsaturated polyprenylcarboxylic acid
．． 56(br,])I) disappears] FD-MASS analysis:
Anhydrous tetrahydro 7 in m/e-x32s three-necked flask
After putting 10 d of run and 100 q of lithium aluminum hydride and cooling to 0°C under nitrogen atmosphere, 1.20 f of the above dihydropolyprenylcarboxylic acid was added to 5 q of anhydrous tetrahydrofuran.
The +wjK solution was added dropwise while stirring.

After the addition was completed, the mixture was stirred at 0°C for 1 hour and then at room temperature for an additional 5 hours.
#r It was poured into aqueous hydrochloric acid little by little and stirred thoroughly. Hexane was added to separate the layers, and the aqueous layer was further extracted twice with hexane. The organic layers were combined, washed with water, washed with heavy water, washed with saturated saline, dried over anhydrous magnesium chloride, and the solvent was distilled off to obtain 1.12f of a colorless liquid.

This product was purified by silica gel column chromatography [using hexane/ethyl acetate = 9010 (volume ratio) as a developing solution] to obtain 1.04F of a colorless liquid. According to the following analytical results, this product has n in the above formula (■).
It was confirmed that Jin is a dolicall with =15.

In analysis: 3320, 2920.2850, 1440
．． 1376°1060.8303-1 1H-NMR analysis (δ and rays): 0.91 (d+3H
) +1.60 (S, 9H), 1.68 (S, 4'8H)
.

i, 10-1.80 (m, 5H), 2.0ff (
b, 7oH).

3.66 (m, 2H) 15.10 (b, 18H)”
C-NMR (pprrv' intensity): 16.006/6
40°17.679/353, 19.5571548
, 23.430/6330°2a3081567.2
5.6771542, 26.43615166°26.
6991548, 26.825/492, 29.316
1528°32.021/456,32.245151
500,37.548,1582゜39.757/68
3,40.0291541.61.2411551.

124.214/445, 124.282/463, 1
24.4481505°124.993/499. ]2
5.07] 15242, 131.210/213°13
4.937/290,135.005A49,135.
229/3567° 135.365/430°

Claims (1)

[Claims] The general formula % represents a unit, -CH2-C-b-C)iz- represents a cis isoprene unit, and n is 11 to 1? represents an integer. ) Polyprenylacetone.