JPS58164564A - Polyprenylnitrile - Google Patents

Abstract

NEW MATERIAL:Polyprenylnitrile of formulaI(formula II is trans-isoprene unit, formula III is cis isoprene unit, n is 11-19). USE:A raw material of drugs or cosmetics: eapecially it is used an a synthetic intermediate of mammarian colichols. PREPARATION:The reaction of polyprenyl halide of formula IV (X is halogen) with an acetoacetic ester of formula V (R is lower alkyl) is carried out in the presence of a base to prepare a polyprenylketocarboxylic ester of formula VI. The product is ketonized and decarboxylated to give a polyprenylacetone of formula VII, further the acetone is subjected to Wittig reaction with a dialkylphosphonoacetonitrile to give the compound of formulaI.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to polyprenyl nitrile. Prenyl nitrile Kll ◎ Polyprenyl nitrile represented by the general formula (1) provided by Takaaki Moto is a substance useful as a raw material for medicines, cosmetics, etc., and is particularly useful as a synthetic intermediate for dolichols. It is useful as

Dolichols were identified in 1960 by R, F, Pennock.
It was first isolated from pig liver by Natu et al.
re (London), 186, 470 (1960)], which was later renamed as a polyprenol-surface mixture having the structure represented by the general formula (A). In formula (A), j representing the number of O cis inopre 7 units is generally distributed from 12 to 181, and j-14, i 5
It has been revealed that homologues of 16 and 16 are living organisms (R, W).

Keenan et al., Biochemi
cal Journal, 165.505 (197
7)] It is known that dolichols are widely distributed not only in Pume liver failure but also in the bodies of mammals, and play an important function in sustaining the life of living organisms. For example, J. B. and Harford et al. conducted in vitro tests using the white medulla of calves and pigs. (Biochemical and Bi
physical ResearchCcmunl
Catian, 76 * 1036 (1977)] 0 The effect of dolichols on promoting the uptake of sugar components into lipids (as in growing organisms) is also noticeable in already mature animals, so it is useful for preventing aging. 0
The function of Dolichol steel in this regard is attracting attention.

9s R, W, Keenan et al. argue that it is important for rapidly growing organisms, such as those in infancy, to ingest dolichol from outside and supplement the dolichol obtained by biosynthesis within the body. (Archives)
of Biochemistry and Biop
hysics.

See '9, 634 (1977)]. Furthermore, when we added dolichol phosphate in the regenerated livers of Akamatsu et al. rats, we found that the amount of dolichol phosphate in the regenerated livers was significantly reduced (even in normal livers), and that the glycoprotein synthesis function in the liver tissue was enhanced. It was found that the function was reduced when dolichol phosphate ester was added externally.9 [Presented at the 54th Annual Meeting of the Japanese Biochemical Society (1981)]0 As mentioned above, dolichol These are substances that control extremely important functions for living organisms, and are useful as pharmaceuticals or their diced forms.
．． You can only get 6t of recall (?, W,
Burgos et Jll, , liochemi
CalJournal, 88, 470 (1963)] 0 It is impossible to completely synthesize dolichols using current organic synthesis technology, as is clear from their complex and unique molecular structures. be. It would be advantageous if dolichols could be obtained by relying on natural products as synthetic intermediates and adding simple synthetic chemical treatments to them;
No such convenient substance has hitherto been found. Conventionally, polyprenols (these are called petula glenol) represented by the general formula (B) [where k = 4 to 6] of the lower rudder have been used as Schiffcampa (Betula verruc).
It is known that the number of cis-made imprene units from these is 14.15 and 1.
#1 It is almost impossible to synthesize dolichols mainly consisting of 6-4 using current organic synthesis technology. MakuX
.

Hannus et al.
reported that the polyprenyl component was isolated at a yield of 1 unit on a dry weight basis from the sheet of estris), and that the core component was a polyprenyl acetate mixture having 10 to 191 m of isoprene units in the cis configuration. (Ph
ytochemlstry, 13, 2563 (1
(974)], their report does not elucidate the details of the trans and cis configurations in axillary polyprenyl acetate. Additionally, D.F.Zinkel
reported the presence of CEO polyprenols containing 18 g of isoprene units in the extract of the leaves of strobe pine (Bibari pine). I'm here (Ph)'tOchemjltry
*11 +3387 (1972)], this report does not provide a detailed analysis of the trans and cis configurations of wrinkled polyprenol.

Some of the inventors and their collaborators F! First, the extracts extracted from ginkgo biloba and Himalayan cedar using an organic solvent are necessarily hydrolyzed to produce 900 100 ml of extracts! Polyprenols containing 14 to 22 imprene units in exactly the same trans, cis configuration as the mammalian dolichols and/or their acetate homologs can be obtained by treatment with thornfine, fractional dissolution, or other suitable separation methods. obtaining a polyprenyl component consisting of a mixture;
The polyprenyl fraction has α-
that the polyprenyl fraction exhibits a distribution of polyprenyl congeners very similar to the distribution of polyprenyl congeners in mammalian dolichols, only in the absence of terminal saturated inbrene units;
It can be relatively easily separated into polyprenyl homologs (with a uniform number of isopres/units), and therefore both the skeleton polyprenyl fraction and each polyprenyl homologue separated therefrom are highly suitable as intermediates for the synthesis of mammalian dolichols. I found out that

In order to efficiently produce mammalian dolichols using the above-mentioned polyprenyl compounds, we have conducted extensive studies on a method of introducing a saturated isoprene unit into the α-terminus of the polyprenyl chain of the polyprenyl compound. The present invention was constructed by creating a polyprenyl nitrile represented by the general formula (1) which is useful as an intermediate in such a method.

The polyprenyl nitrile of the present invention represented by the general formula (1) [hereinafter referred to as polyprenyl nitrile (1) 0] is a polyprenyl nitrile of the present invention represented by the general formula (wherein, X represents a halogen atom and %n is as defined above. 0) Polyprenyl halide [hereinafter referred to as polyprenyl halide (It)]. ] in the presence of a basic compound to form an acetoacetate represented by the general formula (in the formula, B represents a lower alkyl group) [hereinafter referred to as acetoacetate (11)]
It is written as ] and the general formula (F
1/) Polyprenylketocarboxylic acid ester represented by 〇 (in the formula, R and n are as defined above) [hereinafter referred to as polyprenylketocarboxylic acid ester (to). ] is saponified and decarboxylated to produce polyprenylacetone (hereinafter referred to as polyprenylacetone (V)), which is represented by the general formula (in the formula, n represents the predisposition). 0], and can be produced by a Wittig reaction between this and sial-based rufos-containing noacetonitrile.

As mentioned above, polyprenyl halide (■) can be obtained from the extraction of ginkgo biloba or Himalayan cedar *d- directly or through hydrolysis, and has the general formula (in the formula, n is the same as defined above). This halogenation can be easily obtained by halogenating polyprenylene or a mixture thereof with a halogenating agent such as phosphorus trihalide such as P(js% PBr3, thionyl halide such as SOαs, 5OBr2, etc.). The reaction is usually carried out by dissolving the polyprenol in a suitable solvent such as hexanoate or diethyl ether, and adding about -20% to this in the presence or absence of a base substituted by triethylamine, pyridine, etc. ℃
This is done by adding a halogenating agent at ~+50'C011.

Polyprenyl halide (I) and acetoacetate (a
It is preferable to carry out the reaction with ll) in a solvent.

Suitable Kl! Solvents that can be used include diethyl ether,
Examples include ether solvents such as tetrahydrofuran, dioxane, and dimethoxyethane. The amount of solvent used is i
Although not critical, it is 2 to 100 times (by weight), preferably 5 to 80 times (by weight), and more preferably 10 to 50 times (by weight) to polyprenylpalite (seal) K. It is preferable to use a sufficiently dried and good solvent in order for the intended reaction to proceed smoothly. The presence of a basic compound is essential for rounding to carry out this reaction. The basic compounds used include alkali metals such as sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, sodium t-butoxide, potassium t-'butoxide, sodium methoxide, and sodium methoxide. Hydride, hydroxide, metherlytecum, etc. are suitable.
) 1 mole is generally about 0.1 to 504 moles, preferably 0.5 to 3.0 moles, more preferably 0.7 to 1.0 moles.
In a preferred embodiment, the acetoacetate is added to the solution or dispersion of the basic compound, or conversely, the acetoacetate is added to the solution or dispersion of the basic compound. The anion of acetoacetate is first formed by adding the compound all at once or little by little, and then polyprenyl halide (It) is added thereto and reacted.

Acetoacetate (1) and polyprenyl halide (1)
) and the ratio U is not critical, but the ratio is 1/2 to 20/1. Preferably 415-10
/1. More preferably 1/1 to 5/1 WAKFi to form an anion of acetoacetate (1)
, under an inert gas atmosphere such as nitrogen gas or argon -30
It is desirable to carry out the reaction at a temperature of .degree. C. to +100.degree. C., preferably U-10.degree. C. to +80.degree. C., so that the desired anion can be smoothly formed while suppressing p-side reactions. Although the reaction temperature varies depending on the reaction temperature used, a temperature of about 10 minutes to 5 hours at Ii degrees is usually sufficient. Polyprenyl halide (n
) and react. Depending on the reaction conditions used,
Add the entire amount of polyprenyl halide (1) at once)
In some cases, the reaction can be made to proceed smoothly by adding small amounts in portions or dropwise. Addition of polyprenyl halide (It) and +:Ovk
Although the temperature within the reaction system during the trench for completing the reaction is not critical, it is preferably within the range from 10°C to the boiling point of the solvent used. If the reaction temperature 11 degrees is too low, the reaction progresses and it takes too much time to complete the reaction.

On the other hand, if the degree of reaction is too high, undesirable side reactions will proceed.
It is preferable to adopt j. Polyprenyl halide (
The charge is to continue the reaction and stirring of the mixture at the above-mentioned reaction temperature, and the time required for this varies depending on the reaction used, but is usually about 30 minutes. m degrees for a minute 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 (1) by thin-layer I2 mudgraphy.

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. Chromatography is particularly conveniently used. Adsorbents that can be used for chromatography include silica gel, alumina, activated carbon, and cellulose. Among these, silica gel is particularly preferably used. A suitable developing solvent is a mixture of a hydrocarbon solvent such as hexa/pentane, petroleum ether, benzene, etc. and a small amount of a polar solvent such as diethyl ether, chloroform, ethyl acetate, or ethyl alcohol.

It is also possible to omit the ζO isolation step and directly perform the next step of polyprenylacetone (V) 0 synthesis reaction, followed by a purification step.

Polyprenylketocarboxylic acid ester (IV) Fi can be saponified by applying the method conventionally used for the saponification reaction of a111 fatty acid esters. For example, polyprenylketocarboxylic acid ester (IV)
This can be achieved by stirring sodium hydroxide with potassium hydroxide in aqueous methanol, aqueous ethanol or aqueous isopropanol. The amount of sodium hydroxide or potassium hydroxide to be used is about 1.0 to 20.0, preferably about 1.0 to 20.0, based on the amount of polyprenyl ketocarboxylic acid ester (CW).
It is desirable that the amount is 10.07 kg. The above-mentioned hydrous alcohols are suitable as reaction solvents, but hydrocarbons such as hexane, pentane, bene, toluene, etc. It is also preferable to add a small amount of a solvent.In order to make the saponification reaction proceed smoothly, the reaction temperature is from 0°C to the boiling point of the solvent used, preferably 25 to 6°C.
It is most likely to adopt a degree II within the range of 5°C. The time Fi required for the reaction to be completed varies depending on the temperature conditions employed, but is usually within the range of 0.5 to 24 hours.

After carrying out the saponification reaction as described above, the reaction solution is neutralized using a mineral acid such as hydrochloric acid or sulfuric acid, preferably at room temperature or under water-cooled conditions. Under moderately acidic conditions, a decarboxylation reaction automatically occurs to form polyprenylacetone (V). After the decarboxylation reaction is completed, the reaction solution is extracted with hexane, benzene or diethyl ether, thoroughly washed with water, the organic layer is dried, and the solvent is removed.
ll5 products are obtained. In order to purify this product, beam-like mudgraphy is suitably employed. Adsorbents used in chromatography include silica gel, alumina, activated carbon, cellulose, etc.
□ or silica gel is particularly suitable. Developing solvent and L
? Ti hexane, pentane, petroleum ether, benzene,
Preferably, a hydrocarbon solvent such as toluene is mixed with a small amount of a polar solvent such as diethyl ether, diisopropyl ether, chloroform, ethyl acetate, or medel acetate.

Polyprenylnitrile (1) can be produced by reacting polyphosphonoacetonitrile (Witteg reagent) in a sialic acid such as polyprenylace synthesized as described above.

It is a privilege to carry out this Witztech reaction in a solution inert to the reaction, II&. Solvents that can be suitably used include, for example, dimethylformamide, tetrahydro7,
Examples include ran, diethyl ether, and the like. In order for the desired reaction to proceed smoothly, it is preferable that the solvent used be sufficiently dried to an anhydrous state. Furthermore, from the viewpoint of ceramic quality, it is preferable to replace the reaction system with an inert gas such as nitrogen or argon. The amount of molten Go used is preferably 5 to 50 times, particularly 10 to 30 times by weight, the amount of polyprenylacetone used in the reaction.

The ninth step in carrying out the Wittschig reaction is to form a p-phosphoryde by treating the above-mentioned Kuittsch reagent with a basic compound. Examples of basic compounds that can be used here include n-butyl lithium and methyl lithium. Preferred examples include sodium hydride, potassium hydride, sodium methoxide, and sodium ethoxide.

After adding the basic compound selected from these into the above-mentioned solvent, it is heated to -30°C to +80°C, preferably -1θ°C to
While stirring under ILK conditions of +50°C, add the above-mentioned Witschig reagent by dropwise addition, and after the completion of the addition, continue stirring in the above temperature range for about 0.5 to 24 hours to form a phosphorylide. Can be done. At this time, the amount of the basic compound used is approximately 0 relative to the Uitztech reagent.
．． A preferred amount is 5 to 1.57 grams. By adding polyprenylacetone represented by the general formula (V) into this phosphorylide solution and reacting at θ°C to 80°C, preferably 20 to 50°C, ciboriprenyl nitrile (R) can be obtained. The reaction time required to complete the reaction is generally within the range of about 0.5 to 24 hours.The 41! dose of Witstech reagent is polyprenylacetone (V).
0.5 to 10.0 molar equivalent to K, preferably 0.8 to 10.0 molar equivalent
The amount is 8.0 molar equivalents, more preferably 1.0 to &0 molar equivalents. After the Widdehy reaction is completed, the desired crude polyprenyl nitrile can be obtained by pouring the reaction solution into water and extracting the organic layer.

Polyprenyl nitrile (1) C) Purification can be carried out by applying conventionally known separation and purification techniques.

and <K, chromatography is simple and preferable ◇ Adsorbents used in this chromatography include silica gel, aluminium, activated rock, futhrolidyl, cellulose, etc., but silica gel is particularly suitable. As a solvent.

Chloroform, methylene chloride, diethyl ether, diisopropyl ether, methyl acetate,
It is preferable to use a mixture of a small amount of a polar solvent such as ethyl acetate or acetone.

The polyprenyl nitrile (1) of the present invention can be converted into mammalian dolichols, for example, by the synthetic route shown below.

(I) (■) (■) (■) In the above formula, the radical represents a group represented by the formula (in the formula, n is 9 as defined above).

Reaction (■) hydrolyzes polyprenyl nitrile to give polyprenylcarboxylic acid (■).

Reaction (■) is -COt of 1 liter of polyprenyl carbon (■)
Selective hydrogenation of isogrene units having H groups
6, this reaction is carried out in the presence of a hydrogenation catalyst such as, for example, Badgetam type, nickel type, or rhodium thread. The carboxyl group of the a-terminally saturated polyprenyl carbon II (■) obtained in the reaction (■) is removed with aluminum lyticum hydride (reaction), and the a-terminal dolichol # (■) is added. I can get it.

Hereinafter, the present invention will be explained in more detail with reference to Examples and Reference Examples. Note that *IR analysis in Examples and Reference Examples was performed using a liquid film, and NMR analysis was performed using TMS as an internal standard. FD-MAS8 analysis value is 1) (, 11C, 14
N, 110, O which is the value corrected as FIBr #Example 1 Separation of polyprenol
The undried weight) was dried with hot air for 24 hours at 1fJ40°C, and then extracted by immersing it in chloroform 80 at a temperature of about 15°C. Chloroform was distilled off from this extract, and 5 tons of petroleum ether was added to the resulting coagulate to separate the insoluble components. After concentrating the liquid, it was separated using a silica gel column using chloroform as the #1 opening solvent. An oily substance of about 37F was obtained. Approximately 400 slJ of acetone was added to this oil to dissolve the acetone-soluble acid content, the resulting mixture was filtered, the liquid was filtered through 1IIIIII, and the resulting pressure oil was mixed with methanol 4
00m.

2 hours 6 with 40m water and 20F sodium hydroxide
After heating to 5°C, methanol was distilled off, diethyl ether (500 g/) was added to the residue for extraction, the ether layer was washed five times with about 100% water, dried over anhydrous sodium sulfate, and the solvent was distilled off. A 24.2f oil tank was obtained.

This oil was then purified using approximately 114F silica gel.
Separation was performed using a mixture of hexa//isoglobil ether and 90/10 (volume ratio) to obtain 21.8f of oil. This oil is a polyprenol with a purity of 95% or more, and it is used in a semi-preparative liquid chromatography column LiChrosorb RP18-10 (C
1t type) using acetone/methanol-9o/lo
A liquid chromatography analysis was performed using a mixed solvent of (@-violet ratio) as the bath liquid and a water difference refracting needle as a detector, and the area specific gravity of each beater in the obtained chromatogram was determined.Results 1 11 0
．． 32 12 1.13
1 3
&94 14 2&65
15 39.46
1 6 1927
17 19 8 18 1.89
19 0.8
Using this high-performance liquid chromatography, each component was separated from the above oily substance, and the components were identified by the general formula (M) by mass spectrometry, infrared 9&, yield spectrum, 1H-NMR spectrum, and IIc-NMR spectrum. It was confirmed that it is a polyprenol with a structure similar to the following.

Wax field ionization method experimental analysis for each component (yD-MA8S
) results and “H-NMR12) J value was set to 91,
”C-NMROJ[tff2Kt Stop and show L7t.

Reference Example 2 Synthesis of polyprenylploid Boprenol 12,4F of the general formula (M), which is US-15, and viridi/1m were added to 200-n-hexane, and the resulting solution was heated to a rich temperature (approx. 20°C) under a nitrogen gas atmosphere. 2.
After adding phosphorus tribromide to the mixture, the mixture was stirred at mold temperature overnight under an atmosphere of gas. Next, this n-hexane solution was put into a minute funnel, washed three times with about 100 ml of water, and
By drying with anhydrous sulfur #I2 magnesium and adding a medium sulfur solution, a moldy yellow liquid 111E112. Of
When conducting NMR analysis on this material, the signal (d, J-4,08) assigned to the -CHxOH group of the raw material polyprenol disappeared and a new -CH5
Signal belonging to BrKjlill (d, J-3,91
) is an opportunity. Further, when this liquid material was analyzed by FD-MASS, it was m/e-1304. These analysis results confirmed that the above product was a polyprenyl blonde having n-15, X-Br in the general formula (II).

By operating the same machine, polyprenyl bromides with in other than 15 were also synthesized.

Example 1 640"f of anhydrous tetrahydro7ran 3°- and 50-sodium hydride was placed in a three-necked flask, and while stirring at mold temperature, 1.57f of acetate ether was added dropwise. Vigorous hydrogen gas After 9 days, the temperature in the 7th flask was gradually increased while replacing it with phoneme gas, and the mixture was stirred for 1 hour under the refluxing condition of the solvent.Then, the reaction system was heated to fil!
After cooling in an oven, the general formula (II) synthesized according to Reference Example 2 was added with 1/k MI-15, Xwa
A solution of 4.30 f of polyprenyl blonde, which is Br, in tetrahydro7 run (10 m) was added dropwise, and the mixture was stirred overnight using MIi soap. After distilling off the solvent from the reaction mixture using a rotary evaporator, the residue was poured into about 20 g of water and extracted with diethyl ether.

Wash sequentially with heavy water, dry with anhydrous magnesium sulfate,
Diethyl ether was distilled off using a rotary evaporator to obtain a yellow liquid. This yellow liquid was heated to 1-3 at 150°C under reduced pressure.
Heating for 0 minutes to remove low-boiling components, the residue was purified by silica gel, Lamb Chromadog 2F [hexane/ethyl acetate=
9872 (volume ratio) was used as IIkl#I liquid]
Purification was performed to obtain a pale yellow liquid 2.48F. The analysis results of this item are shown below. O IR analysis +1740.1715,1660.830 pieces-
1p disorder"H-NMR analysis: J 1.21 (3H,
t, -COsCkhCHs).

C(J< 4.11 (2H, q, -CoIC!!2CH3)
According to the analysis results of FD-MAS8 analysis: m/e = 1354, this slightly yellow liquid has n in the general formula (IV).
-15, n=C2HJl-1'' was confirmed to be ethyl 4ulfoliprenylketocarboxylate.

Next, this ethyl polyprenylketocarboxylate was added to a solution of 0.5f% sodium hydroxide, 20117 ethanol, and 5d water, and stirred for 3 hours under reflux conditions. The residue was poured into about 20 ml of water, acidified to 2 ml by adding chain hydrochloric acid in portions, 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 product was purified by silica gel column chromatography [using hexane/ethyl acetate - 98/2 (volume ratio) as the developing solution] to obtain a pale yellow viscous liquid of 1.98F.
I got it. The analysis results of this item are shown below.
MR analysis t I ppm Cα41.53 (8,9H), 1.62 (8,48H)
.

1.7-4.4 (m, 751(), 5.05(
br, 18H) FD-MA88 analysis richness m/'! -1
According to the analysis results of 282 or more, this slightly yellow liquid has the general formula (
V) was confirmed to be polyprenylacetone with nm15.

Then add 40-40% of anhydrous tetrahydrofuran to the three-layer
and 50-sodium hydride 220 cape, rich ■
1. Add diethylphosphonoacetonitrile without stirring. O
A solution of 10-f dissolved in anhydrous tetrahydrofuran was added dropwise. After the addition was completed, stirring was continued for another 1 hour at II1 temperature, and then a solution of polyprenylacetone 1.92F, which is n-15 in general formula (V), in anhydrous tetrahydro 7 run 1011 dKfII was added dropwise at l[temperature]. After the addition was completed, the mixture was stirred at lukewarm temperature for 30 minutes and then further stirred at 50-60°C for 3 hours. Next, the reaction solution was cooled to a mold temperature of 100 liters, and after adding about 1 wL of water, tetrahydrofuran in the reaction solution was distilled off using a rotary evaporator. About 5011 L of water was added to the residue, and the mixture was extracted with hexane. The hexane layer was washed with tan brine, dried over anhydrous magnesium sulfate, and the hexane was distilled off to obtain a yellow liquid. This liquid was subjected to silica gel column chromatography [hexane/ethyl acetate-9
8/2 (volume ratio) was used as a developing solution] to obtain a colorless liquid of 1.72F. This product was confirmed to be polyprenyl nitrile with n=15 in the general formula (1) according to the following analysis results.

IR analysis! 2220.1660 (weak), 162
5.1440゜1375.830 scratch m 19m "H-NMR analysis δ 1.53 (1,9H), 1
．． 62(8,48H)Cα4 1.7-2.5(m, 75H), &05(br, 19H
) FD-MA8S analysis tm/e-1305 By the same operation, 15 where n is between 11 and 19 in general formula (II)
A polyprenyl nitrile represented by the general formula (1) having a corresponding value of n was synthesized from a polyprenyl nitrile having a value other than the above. Their yields were approximately the same as those obtained when n-15 polyprenyl nitrile was synthesized. Also, those! The characteristic absorption in the R spectrum and the characteristic signal in the NMR spectrum substantially corresponded at that position to that of the above polyprenyl nitrile with n;15. Furthermore, the results of FD-MAS8 analysis are as follows: Raw material polyprenyl bromide (It) Onom m/e of produced polyprenyl nitrile *1
1 103312
110113
116914
123716 137g1
7 144118
150919
1577 Example 2 Witzig test Hata diethylphosphonoacetonitrile (1,
or) in place of dimethylphosphonoacetonitrile 0.
The same operation as in Example 1 was performed using 84F to obtain 1.7O
A colorless liquid of f was obtained. IR portion of this #,”)I-
The results of NMR analysis and F'D-MASS analysis completely coincided with those of the polyprenyl nitrile which is n-15 in the general formula (1) obtained in Experiment 1.

Procedural amendment (spontaneous) 1. Indication of the case Patent application No. 47458 of 1982 2. Name of the invention l librenyl nitrile (108) Rira Co., Ltd. Shijun decoy role Tsuguo Okabayashi 4, agent Aoeyama, Sakazu, Kurashiki City 2045-1 Rira Shi Co., Ltd. Tel: Tokyo 03 (277) 3182 5. Subject of amendment & Contents of amendment (1) "Chloroform" in line 42 from the bottom of page 21 of the specification. Insert Jt between rIJ and .

(2) The following Example 5 is added after "matched." on the bottom line of page 55 of the specification.

[Example 5 In the general formula (b) obtained in the same manner as in Reference Example 1, n
A polyprenyl bromide mixture is prepared by reacting a polyprenol mixture with a distribution of from 11 to 19 and an O composition substantially equal to that described in Reference Example 1 with phosphorus tribromide according to the method of Reference Example 2. and that 4.30 f
By carrying out exactly the same operation as in Example 1, except that in the general formula (6) of Example 1, polyprenyl bromide 4.5Of where n=15 was used, a colorless viscous final product was obtained. 1.67 f of liquid was obtained.

The IR,'H-NMR analysis results of this product were substantially the same as those obtained for the polyprenyl nitrile of Example 1 in terms of characteristic absorption and position of characteristic signals.

”

Claims (1)

[Claims] general formula (5 Ya, Shi, Akira ((H3-□, 73 Nada I, Pu, 2 Ru represents an integer from till to 19. ) Polyprenyl nitrile represented by 0