JPH0454141A - Chain terpene compound - Google Patents

Abstract

NEW MATERIAL:A chain terpene compound of formula I [R<1> is H, 1- alkoxyalkyl, tetrapyranyl, tetrahydrofuranyl, acyl, group of formula II (R<3> to R<5> are 1-10C alkyl, phenyl); R<2> is group of formula III or IV [R<6> is H,CO2R<7>; R<7> is 1-4C alkyl; but when R<1> is H, R<6> is not H, and when R<1> is 1-ethoxyethyl, R<7> is not CH3; R<8> is-CidenticalCH,-CH=CH2)]. EXAMPLE:Ethyl 2-acetyl-5,6-dimethyl-10-(2-tetrahydropyranyl)oxy-4, 8-decadienate. USE:An intermediate enabling to profitably prepare Sarcophytol A having an anti-carcinogenesis-promoting action and an antitumor action. PREPARATION:The hydroxyl group of a compound of formula K is protected and the prepared compound of formula L is subjected to a nucleophilic substitu tion reaction with acetoacetic acid ester alkali metal salt to provide the com pound of formula Ia.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a novel chain terpene compound.

Specifically, the compound of the present invention exhibits anti-carcinogenic promoter activity (C
ancer 5urveys, 2.540 (198
3): Metabolism, VO125 Special Issue Cancer '88.3 (+9
The present invention relates to a novel substituted chain terpene compound which is an intermediate for the production of sarcotuitol A and has antitumor activity (Japanese Patent Publication No. 63-20213).

(Prior art) Sarcotuitol A represented by the following structural formula is
A total of four reaction routes containing one conjugated double bond in the four-membered ring. Cembrene, which has one double bond, is a diterpene alcohol.

Sarcophytol A Until now, no method for synthesizing Sarcophytol A was known, but we previously proposed a synthetic method as shown in reaction route 1 below (Japanese Patent Application No. 1-181710).

(E) (F) Trimethyl (J) Sarcophytol A In the above formula: R9 is C, C, lower alkyl or phenyl group,
X is a halogen atom or 050. A leaving group such as R12 (R1
2 represents a lower alkyl group such as a methyl group or an ethyl group, a substituted alkyl group such as a trifluoromethyl group, a phenyl group, or a substituted phenyl group such as a tolyl group or a mesityl group)
and RIG is a trimethylsilyl group, a 1-ethoxyethyl group, or a hydrogen atom.

(Problems to be Solved by the Invention) The method for synthesizing compound (F), which is an intermediate in the above-mentioned sarcophytol A synthesis route, requires expensive E having the steric configuration necessary for sarcophytol A synthesis.

E-fufurnesal (A) is required, and (B)
Since there is a major problem in that oxidation of the terminal position with selenium dioxide, which is not high in regioselectivity or yield, for J2, we developed an industrially advantageous synthetic method for compound (, F) as an alternative to this method. was desired.

(Means for Solving the Problems) The present inventors aim to provide an industrially advantageous manufacturing method for sarcophytol A by developing a method for synthesizing compound (F) that can solve the above problems. As a result of intensive study on the purpose, it was discovered that the chain terpene compound of the present invention is a useful intermediate in the synthetic route of sarcophytol A that can achieve this purpose, and the present invention was achieved.

That is, the gist of the present invention is the following general formula (I) (wherein R1 is a hydrogen atom, a l-alkoxyalkyl group, a tetrahydropyranyl group, a tetrahydrofuranyl group, an acyl group, or R, -5i- (wherein R 'R'', R' and R' each independently have 1 to 1 carbon atoms
0 alkyl group or phenyl group) or -Co, R' (in the formula, R7 represents an alkyl group having 1 to 4 carbon atoms. However, when R1 represents a hydrogen atom, R6 represents a hydrogen atom , and when Rl represents a 1-ethoxyethyl group, R7 does not represent a methyl group)]] is -C-CH2) exists in

Hereinafter, the present invention will be explained in detail.

The compound according to the present invention is represented by the above general formula (I). In the general formula, R1 is a hydrogen atom, a l-alcokyne alkyl group, a tetrahydrofuryl group, a tetrahydropyranyl group,
It represents an acyl group or a group represented by R'-5i-, and examples of the 1-alcokyne alkyl group include l-ethynethyl group, metkynemethyl group, etc., and examples of the acyl group include acetyl group, benzoyl group, etc. Examples of the group represented by R'-5i- include trimethylsilyl, dimethyltert-butylsilyl, diphenyltert-butylsilyl, and the like. R2 is (R7 is a methyl group,
(represents an alkyl group having 1 to 4 carbon atoms such as an ethyl group), but when R1 represents a hydrogen atom, R6 does not represent a hydrogen atom, and when R1 represents a 1-ethoxyethyl group, R7 represents a MeCEC or -CH=CH2). Specific examples of the compound represented by general formula (1) are shown below.

Specific example of general formula (1) MOM HP -5i(CH3)2c41(*’ c. oph CHzOCHs (=MOM) 15i (CHI) IC4HI’ 5i (CHs) x CJ*’ -COCH3(-AC) QC2H.

-Co, CH.

-CO, CH.

0zCJs -CO, CH.

-Co2CO.

EE HP MOM Si(CH,)2C,H4' H Ac CoPh EE HP CH:CH2 CH=CH.

CH=CH.

-CH-CH2 CH-CH.

-CH= CHx -CH-CH2 C=CH C=CH CHCHs("EE) 24 -MOM -c=cH2
5S+(CHJ2C-H9' C=CH26-
H-C=CH26-Ac -C=CH28-C
oPh -C==CH Next, the method for producing the compound of the present invention will be explained.

The compound represented by the general formula (1) is, for example, known document C.
J,Am,Chem,Soc,,99,5525(19
[77)]] It can be produced from 8-hydroxygeranyl acetate [compound (K)] produced by the method below according to the synthetic route shown below.

(K) (In the formula, R1, R7 and R8 are as defined above.) (2) A method for producing an R'-1-alcokyne alkyl group, a tetrahydropyranyl group, a tetrahydrofuranyl group, and a metal article.

For example, 0 to 8-hydroxygeranyl acetate (K)
．． 1 to 10 equivalents of 1 to 1 to haloalkyl ethers such as chloromethyl methyl ether and chloromethyl-2-methoxyethyl ether are mixed with halogenated solvents such as methylene chloride and chloroform, etheric solvents such as styrene ether and tetrahydrofuran, or ethyl acetate. In a solvent such as dimethylformamide or without a solvent, 0.5 to 10 equivalents of a metal hydride such as sodium hydride or potassium hydride, amines such as triethylamine or diisopropylethylamine, or pyridine, etc. as a base of 120 to +100
Alternatively, 0.1-10 equivalents of vinyl ethers such as ethyl vinyl ether and dihydropyran are added to a catalytic amount of mineral acids such as hydrochloric acid and sulfuric acid, p-toluenesulfonic acid, camphorsulfonic acid dichloromethane,
A method of reacting at -20 to +100°C in a halogenated solvent such as chloroform, an ether solvent such as ethyl ethyl tetrahydro-7, or a solvent such as ethyl acetate or dimethylformamide, or without a solvent;
1-1o equivalent of trimethylsilyl chloride, dimethyl tert-butylene chloride, or other halogenated trialkyl chloride is mixed with a halogen solvent such as methylene chloride or chloroform, a hydrocarbon solvent such as hexane or benzene, or an ether solvent such as diethyl ether or tetrahydrofuran. 0.1 to IO equivalent of a nitrogen-containing compound such as triethylamine, dimethylaminopyridine, imidazole, or a metal hydride such as sodium hydride or potassium hydride in a solvent or a solvent such as ethyl acetate, dimethylformamide, or dimethyl sulfokide. -20 to +100° as a base
By a method of reacting with C for 5 minutes to 24 hours, R1 is a 1-alkoxyalkyl group, a tetrahydro7ranyl group, or a tetrahydropyranyl group, R''-5i- (R' to R5 are as described above). Compounds of the formula S (as in In the presence of a valent palladium complex catalyst, a metal hydride such as sodium hydride or a strong base such as n-butyllithium or lithium diisopropylamine is added to an acetoacetate such as ethyl acetoacetate or ethyl acetoacetate with diethyl ether, tetrahydrofuran, or dimethylformamide. A method of reacting an alkali metal salt of acetoacetate, which can be prepared by reacting at -70 to +100°C, in an aprotic polar solvent such as dimethyl sulfoxide at -70 to +100°C for 30 minutes to 48 hours. Accordingly, in the general formula (1), R1 is a l-alkoxyalkyl group, a tetrahydro-7ranyl group, a group represented by (R1-R8 are as described above), R
2 can produce compounds.

A method for producing a compound that is an alkyl group).

For example, (I) produced by the above method (2) [R'=1-alkoxyalkyl group, tetrahydrofuranyl group, or tetrahydropyranyl group, R2-kylammoniums, or by a method of reacting with hydrofluoric acid, etc. be able to.

○ 0.1-10 equivalents of hydrochloric acid, a mineral acid such as WL acid, a strong organic acid such as para-toluenesulfonic acid, or a pyridinium salt of para-toluenesulfonic acid in an alcoholic solvent such as ethanol, water, or a mixed solvent thereof. It can be produced by a method in which a salt of a strong acid such as Also (I
) [R'=-3i-R' (R7 is as described above)] in a protic polar solvent such as methanol, ethanol, and water, an ether solvent such as diethyl ether and tetrahydrofuran, or a mixed solvent thereof, at 0. 1 to 10 equivalents of 7.
A method for producing a compound represented by a tetraal (as described above) such as tetrabutylammonium heptaide.

(R? is as described above)] in the presence of 0.1-10 equivalents of a base such as triethylamine or pyridine, an acyl halide such as acetyl chloride or benzoyl chloride, or an acid anhydride such as acetic anhydride. -20 to +1 using a halogen solvent such as dichloromethane, an ether solvent such as diethyl ether, or a hydrocarbon solvent such as benzene or n-hexane, or without using a solvent and using a base as a solvent.
It can be manufactured by a method of acting at 00°C.

■R dish=Hydrogen atom, l-alfukidialkyl group, tetrahydrofuranyl group, tetrahydropyranyl, metal hydroxide such as potassium hydroxide and O~100°C for lO min~24
A manufacturing method for a time-reacting hydrolysis method.

For example, compound (I) produced by the above methods
[R' = hydrogen atom, 1 to alkoxyalkyl group, tetrahydrofuranyl group, tetrahydropyra group) 1 is an ether solvent such as diethyl ether or tetrahydro7rane,
Protic polar solvents such as methanol, ethanol, water, etc.
Or in a mixed solvent thereof, 0.1-10 equivalents of sodium hydroxide, after complete preparation, IO
The decarboxylation method involves a time reaction, or the decarboxylation method involves a reaction with 0.1 to 10 equivalents of a metal halide such as sodium chloride or sodium iodide in an aprotic polar solvent such as dimethylformamide or dimethyl sulfoxide at 50 to 250°C. It can be produced by a method using a carboalkoxylation reaction.

■H1 = hydrogen atom, l-alkoxyalkyl group, tetrahydro-7ranyl group, tetrahydropyranyl group, R'-5
i- (R' to R5 are as described above), R2-CH.

For example, an ether solvent such as diethyl ether tetrahydrofuran, or n
- in a hydrocarbon solvent such as hexane or benzene, 0.1-
It can be produced by an addition reaction in which 10 equivalents of vinyl anion such as vinyllithium or vinylmagneneum bromide is allowed to react at -50 to 100°C for 30 minutes to 48 hours.

(2) It can be produced by an addition reaction in which R1-hydrogen atom, l-alkoxyalkyl group, tetrahydro-7ranyl group, and tetrahydro-7ranyl cetylide are reacted at -50 to +100°C for 30 minutes to 48 hours.

For example, CH produced by the method of (1) or (2) above.

For example, an ether solvent such as diethyl ether, tetrahydrofuran, or
- in a hydrocarbon solvent such as hexane or benzene, 0.1-
10 equivalent metal acetylide, ethynylmagnesium bromide, etc.

In the presence of 0.1-10 equivalents of a base such as triethylamine or pyridine, 0.1-10 equivalents of an acyl halide such as acetyl chloride or benzoyl chloride or an acid anhydride such as acetic anhydride are dissolved in a halogenated solvent such as dichloromethane or diethyl chloride. It can be produced in an ether solvent such as ether, or a hydrocarbon solvent such as benzene or n-hexane, or by a method in which the reaction is carried out at 20 to +100°C using a base that also serves as a solvent without using a solvent.

By using the compound of the present invention, the key intermediate (F) in the sarcophytol A synthesis route described in the above-mentioned Japanese Patent Application No. 181710 can be obtained using an inexpensive and easily available monoterpenoid as a starting material, for example, by the following method. By the route exemplified in Reaction Route 2, it can be produced more advantageously than conventionally.

Reaction route 2 Synthesis route of sarcotuitol A (A'
) Sarcotuitol A (wherein R1 and

The compound was dissolved in a hydrocarbon solvent such as undecane or xylene, bis[2- A method using a rearrangement reaction in which R1 is reacted in an ether solvent such as (2-methoxyethquin)-ethyl]ether or mineral oil at 100 to 300°C for 30 minutes to 24 hours, or, for example, in general formula (1), R1 is It is represented by a 1-alkoxyalkyl group, and is pyridinium chloro at 0 to 100°C in a solvent such as R2 methylene, chloroform, a hydrocarbon solvent such as n-hexane, benzene, or dimethylformamide. Unsaturated aldehydes (
A') can be prepared, and (A') can be prepared using WittigHorner, e.g. Reagents include ether solvents such as diethyl ether and tetrahydrofuran, n
- W as a base at -100 to +100°C in a hydrocarbon solvent such as hexane or toluene or an aprotic polar solvent such as dimethylformamide or dimethyl sulfoxide.
1 equivalent or less of sodium hydride relative to the Ittig reagent;
Anion generated by reacting metal hydrides such as potassium hydride, organometallic compounds such as n-butyllithium and lithium diisopropylamide, and metal alkoxides such as sodium methoxide and t-butoxypotassium at temperatures of -100 to +100°C. Compound (B'') can be produced by a method of treating (B'') with 0.1-10 equivalents of a metal such as lithium aluminum hydride in an ether solvent such as diethyl ether or tetrahydrofuran. Hydrogen complex compound at -70~+100°C
Alternatively, in a hydrocarbon solvent such as n-hexane or benzene, 0.1 to 10 equivalents of a metal hydride such as diisopropylaluminium hydride is reacted with -70 to +1
Aldehyde (C) can be produced by a method of reacting at 00°C for 5 minutes to 5 hours, and from this aldehyde (C) can be prepared by reacting it in, for example, aqueous methanol, aqueous ethanol, aqueous tetrahydrol, or a mixed solvent thereof. 1-10
Alcohol (D') can be produced by a method of reacting with an equivalent amount of a mineral acid such as hydrochloric acid or sulfuric acid, a strong organic acid such as para-toluenesulfonic acid, or a salt of a strong acid such as pyridinium salt of para-toluenesulfonic acid. (D'') A method of halogenating allyl alcohol without allyl rearrangement, for example, 0.1-1o equivalent of carbon tetrahalide in the presence of 0.1-10 equivalent of triphenylphosphine,
In a solvent such as acetonitrile or dichloromethane, or in the case of chlorination, carbon tetrachloride is used as a solvent, and
0.1-10 equivalents of methanesulfonyl chloride, p
-Sulfonyl halides such as toluenesulfonyl chloride and metal halides such as lithium chloride are combined with pyridine,
-40 to +3 in the presence of bases such as S-collidine and lutidine
Compound (F) of reaction route 2, which is a key intermediate in the synthesis route of sarcotuitol A described in Japanese Patent Application No. 1-181710, can be produced by a method such as allowing the reaction to occur at a temperature of 0°C for 1 to 12 hours. , (F) according to the method described in Japanese Patent Application No. 1-181710.

That is, among the compounds represented by compound (G) in Reaction Route 1, the compound in which R10 is a trimethylsilyl group can be prepared using a solvent such as methylene chloride, chloroform, or ethyl acetate from compound (F) produced by the above method. In the presence of a catalytic amount of metal cyanide-18-crown-6-ether complex, equivalent to 10 equivalents of trimethylsilyl nitrile in medium or without solvent at -20 to 50°C for 30 minutes to
It can be produced by reacting for 5 hours, and after dissolving this compound in a solvent such as tetrahydro7ran or methanol, 061
~3N aqueous mineral acid solution such as hydrochloric acid or sulfuric acid at θ℃~room temperature,
R16 is hydrogenated by a method of reacting for 5 minutes to 5 hours, or a method of reacting with a catalytic amount to 10 equivalents of tetraalkylammonium such as tetrabutylammonium fluoride in a solvent such as tetrahydrofuran or dioxane at 20°C to room temperature. A cyanohydrin compound, which is an atom, can be produced. A compound in which R'' is a 1-ethoxyethyl group is prepared by adding 10 equivalents of ethyl vinyl ether in a solvent such as ethyl ether or ethyl acetate to a catalytic amount of a mineral acid such as hydrochloric acid or sulfuric acid,
It can be produced by a method such as allowing the reaction to occur at -20°C to room temperature for 30 minutes to 5 hours in the presence of a strong organic acid such as para-toluenesulfonic acid or a salt of a strong acid such as a pyridinium salt of para-toluenesulfonic acid.

Among the compounds (G) in the above route, compounds in which R10 is a trinotylsilyl group or a J-ethoxyethyl group, ether solvents such as ethyl ether and tetrahydrofuran, aromatic hydrocarbon solvents such as benzene and toluene, etc. Alternatively, in a saturated hydrocarbon solvent such as n-hexane or n-heptane, add an equivalent to 1O equivalent of a base such as lithium diisopropylamide, lithium bis(trimethylsilyl)amide, or sodium hydride at -70 to +100°.
Among compounds (H), a compound in which R" is a trimethyl-7lyl group or a l-ethoxyethyl group can be produced by reacting with C for 5 minutes to 10 hours, and a solvent such as tetrahydrofuran or methanol can be produced. Medium, 0.
A method in which a mineral acid aqueous solution such as 1 to 3N hydrochloric acid or sulfuric acid is allowed to react at 0°C to room temperature for 5 minutes to 5 hours, or in a solvent such as tetrahydrofuran or dioxane at -20°C to room temperature.
A compound in which R1° of compound (H) is a hydrogen atom can be produced by a method in which a catalytic amount to 10 equivalents of tetraalkylammonium such as tetrabutylammonium fluoride is reacted.

For compound (H), from a compound in which RIG is a hydrogen atom, a solution of the organic solvent such as ethyl ether or ethyl acetate is reacted with an aqueous solution of sodium bicarbonate at Q'C to room temperature for 5 minutes to 5 hours. By operation or from a compound in which R'' in compound (H) is a trimethylnryl group, hydrous tetrahydrofuran,
It can be directly converted into a ketone body, compound (J), by a method such as a method of reacting a catalytic amount to an IO equivalent of a tetraalkylammonium fluoride such as tetrabutylammonium fluoride in a solvent such as dioxane. dibutyl hydride at -70 to +50°C in an ether solvent such as ethyl ether or tetrahydrofuran, an aromatic hydrocarbon solvent such as benzene or toluene, or a saturated hydrocarbon solvent such as n-hexane or n-hebutane. Sarcophytol A can be produced by a method of reacting a metal hydride such as aluminum or a metal complex compound such as lithium aluminum hydride in an amount of equivalent to 1 O for 5 minutes to 5 hours.

The above-mentioned synthetic route for sarcophytol A using the compound of the present invention as an intermediate is an industrially superior route for the production of sarcophytol A, and therefore the compound of the present invention is extremely important for that purpose. It is a synthetic intermediate.

(Example) The present invention will be explained in more detail with reference to Examples below.
The present invention is not limited by the following examples unless it exceeds the gist thereof.

Synthesis Example 1 A dichloromethane solution (6i) of 8-acetoquine-2,6-dimethyl-2,6-octadien-1-ol (1,81L8.52mmol) and dihydropyran (1,17mL12-8mmo+) was stirred, and Para-toluenesulfonic acid (40 mg) was added and stirred at room temperature for 30 minutes. Saturated soda water (30 mQ) was added to the reaction solution, and the product was extracted with hexane-ether (5/1.2X30 mQ). After drying the extract over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting residue was purified using phosphoric gel column chromatography to obtain 1-acetoxy-8-(2-tetrahydropyranyl)oxo-3, fucymethyl-2. 6-
Octadiene (2.42 g, 96%) was obtained.

IR (film) cn+-';2'150.2880.
1742.1230.1020' HN M R (CD Cl s , 250 M
Hz) δppm: 1.

45-1.92 (m, 6H, 0CHz-CHi-CH2
-CH2-CH20),'l,66.1.71(2s
,6H.

(CHs)C=CHx2), 2.06(s, 3H, QC
OCHs), 2.002-2-25(,4H,C-CH
-CH, -CH, -), 3.51 (dt, J-11,4
, 4°7Hz, IH, -0CHaHb-CH2-), 3
．． 85.4°10 (2d, J-114Hz, 2H, 0C
H2 (CH), 3.80-3.94 (+n, l H,0
CHaHb-CH2), 4.59 (d, J=7.1Hz
, 2H, -c=cHCHzO), 5.35(t, J-7
, 2Hz, IH, -CH5C-CH-95-41 (t,
J = 6-8 Hz, lH.

CH, C=CH-).

Synthesis example 2 OAc 0Ac8
-acetoxy-2,6-dimethyl-2,6-octadien-1-ol (110 mg, 0.52 mmol), triethylamine (0,25++lL1.83 mmol)
, chloromethyl-methyl ether (0,069 mff,
0.92mmo + ) in acetonitrile solution (2mQ
) was refluxed for 4 hours with stirring. Water (3
mQ') was added and the product was extracted several times with ether (5 mQ). After drying the extract (anhydrous magnesium sulfate) and distilling off the solvent under reduced pressure, the resulting crude product was subjected to silica gel column chromatography to obtain the desired l-acetoxy-8-(methoxymethyl)oxo-3,fusimethyl- 2.6-octadiene (109 mg, 82%) was obtained.

IR (film) cm-'; 3000, 2940, 29
00.1742i 440. +380.1365,1
230.1150.1100,1047.1025゜9
50.918゜'HNMR (CD CI3.250 MH2) δppm
;t.

67.1.71 (s, 6H, 2xCH, C=CH-),
2°06 (s, 3H, ococHs), 2.05-2.
25 (m, 4H, -C=CH-C searim-C=CH-
).

3.38 (s, 3H, CHxO), 193 (s, 2H,
OCC = CH-), 4.59 (d, J = 7-2Hz
, -CdanxOcOcHs), 4.62(s, I H,C
HsOCHiO), 5.30-5.45 (m, 2H, 2
x-C=CHCH2-).

Synthesis Example 3 A dimethylformamide solution (4i) of 8-acetoxy-2,6-dimethyl-2.6-octagenin-1-ol (526m9.2.48mmol) was stirred on a water bath, and imidazole (338mg, 4.96mmo+) and Chlorodimethyltert-butylsilane (410mg,
2.73 mmol) was added, and the reaction solution was diluted to 1.2 mmol at room temperature.
Stir for hours. Water (30 mn) was added to the reaction solution, and the product was extracted with hexane (20 mcx2). After drying the extract (anhydrous magnesium sulfate), the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel chromatography to obtain l-
Acetoquine-8-(dimethyltert-butylsilyl=2.6-octadiene (605mg.75%)
is obtained.

IR (film) cm-'; 2950, 2930, 28
90, 2850.1743. l 460.1380.1
360, 1245.1230, 1105.1065.

1020, 830,770,660-'H NMR (CDCls.250MHz) δp
pm; 0.

06(s, 6H, (CHz)zsi), 0.9 1(s
, 9H, (CH3)3C Sl), l −6 0 ,
1 1 1 (2s, 2×C=CH), 2.
06 (s, 3H, OCOCHs), 2.03-2.22
(+++, 4H, -C=CH-Cdan, -Cdan.

C=CH-), 4. OO(s.2H,SiOCdan,C=
=CH-), 4.5 9(d, J-7.1 Hz,
2H. -C-CH CHxO ), 5.36 (m,
2H,2xC=CHCH2').

Example 1 O2Me Under a nitrogen atmosphere, a tetrahydrofuran solution (6 mQ), triphenylphos 7 (
(105mg, 0.4mg) and tetrakis(triphenylphosphine)palladium (168mg).

0,15 mmol) and stirred at room temperature for 15 minutes.

To this mixture was added sodium hydride (305 mg.12).

7mmol1) and methyl acetoacetate (1.57mmol12.1
A tetrahydrofuran solution (25+nQ) of the sodium salt of methyl acetoacetate prepared from 4.6 mmol) was added, and the reaction mixture was refluxed for 5 hours. Add water (10
After adding mQ) and ether (301110) and stirring well, the organic layer was separated. The aqueous layer was immersed in ether (5 m
Q) and the extract was dried over anhydrous sodium sulfate. The solvent is distilled off under reduced pressure, and the resulting residue is purified by silica gel column chromatography to obtain methyl 2-acetyl-5,9-dimethyl-10-(2tetrahydropyranyl)oxy-4,8-decadienofluoride ( 1.06g.8
3%) was obtained.

IR (film) cm-'; 2950, 2870.1
750, 1722.1440, 1360.1201, 1
150, 1022.

NMR (CDCls.250MHz) δppm; l
, 4 5 ~ 1 , 9 2 (m, 6 H, C (○) Hz
CH2 CH2 CH2 CHO), 1.
63.1-65 (2S, 6H.2XCH, C=CH-)
, 1.94-2.1 5 (m.4H.

- C ” C H C H z C H 2 -
C-CH), 2-22(s,3H
, CHsC-0), 14 6(t, J-7.5Hz, l
H, -CHC○2), 3.5 3(m, LH,
-, CH. -CHaHb-0-), 3.73 (s.3
H.C.O. Hz), 3.83.4.09 (2d, J=
l 1.8Hz. 2H.

-OCH, C=CH-), 3.82-3.94 (m, l
H.

CH2 CHaHb-○-), 4.60 (t, J-3
．． 4Hz, LH, -OCHO-), 5.04 (t, J=
7.3Hz. lH. C=CHCH2), 5
．． 38 (t, J-6.2Hz, IH, -C=CHCHx
)-Tora flow side 2 02Me Under nitrogen atmosphere, 1-acetoxy-8-(methoxymethyl)okino3. Fushimethyl-2,6-octadiene (
600mf! , 2.34 mmol) of tetrahydro7
Triphenylphosphine (
60 mg, 0.23 mmo+) and tetrakis(triphenylphosphine)palladium (I O8 mg, 0.
09 mmol1) was added thereto, and the mixture was stirred at room temperature for 15 minutes. Add sodium hydride (225u, 9.36mmo) to this mixture.
l) and methyl acetoacetate (1.26 mQ, l 1.7
A tetrahydro 7 run solution (25 m(2)) of the sodium salt of methyl acetoacetate prepared from methyl acetoacetate was added, and the reaction mixture was refluxed for 2 hours.
) and ether (50 cod) and stir well,
The organic layer was separated. The aqueous layer was extracted with ether (50 mQ), and the extract was dried over anhydrous sodium sulfate. The solvent is distilled off under reduced pressure, and the resulting residue is purified by silica gel column chromatography to obtain methyl 2-acetyl-5,9.
-dimethyl-1O-(methochinomethyl)oxy-4,8
- Decadier inert (670 mg.

92%) was obtained.

IR (film) c+n-': 2930.1745,1
720.1438, 1355.1208, 1150, 1
100.1040.920゜'HNMR (CDCl2, 250MHz) δppm;
1.

63.1-65 (2s, 6H, CHsC=CHx2).

1.93-2.17 (m, 4H, -C=CH-CH2C
H2C-CH), 2.22 (s, 3H, COCHs).

2.56Q, J=7.4Hz, 2H, -C=CH-CH
, -CH(CO2CH3)-), 3.38(s, 3H,
Cdanyu0CHxO)-3,46(t, J=7.5Hz,
IH.

CH(CO2CH3)), 3.73(S, 3H, C02
CH3) 3.92 (s, 2H, -OCH, C=CH-)
, 4.61 (s, 2H, 0CHzO), 5.04 (t,
J=7.3Hz, IH, C=CHCHz), 5.3
8(t, J-6,7Hz, lH, C=CHCHx'
) Example 3 Ac CO,Me Under nitrogen atmosphere, 1-acetoxy-8-(dimethoxytert-butylsilyl)oxy-3,7dimethyl-2.
6-octadiene (600rng, 1.84mmo+
) in tetrahydrofuran solution (5 mQ), triphenylphosphine (47 mg, 0.18 mmol) and tetrakis(triphenylphosphine)palladium (81
mg, o, o 7 mmol) and stirred at room temperature for 15 minutes. Add sodium hydride (92 mg,
8,0 mmol) and 7ce) acetic acid) methyl (0,99
m11.9.

A solution of sodium salt of methyl acetoacetate prepared from 20 mmol of sodium salt in tetrahydro7ranine (C20 mQ) was added, and the reaction mixture was refluxed overnight. Water (lO+++Q
) and ether (30 ml) were added and after stirring well, the organic layer was separated. Ether the aqueous layer (5 stomachs 4x2)
The extract was dried over anhydrous sodium sulfate.

The solvent is distilled off under reduced pressure, and the resulting residue is purified by silica gel column chromatography to obtain methyl 2-acetyl-10-(dimethyltert-butylsilyl)-oxy-5,9-dimethyl 4,8-decadiene ( 620
mg, 88%) was obtained.

IR (7(lum) cm-'; 2970.2940.29
10.2860.1745.1722.1435. ]3
60.1250.1065,837,775゜'HNM
R (CDC13+ 250 MHz) δppm; 0
.

06, (s, 6H, (CHs)xsi), 0.90(s
, 9H, (CH3)3C5l), l -59,1,63
(2s, 6H, 2xCdan3C=CH), 1-92~2.
15(m, 4H, C=CH-CH, -CH coco-=CH
-), 2-22 (s.

3H, CHCH3), 2.55(L, J-7, 4H2,
2H, -C-CH-C (:H(C02CH3)),
3゜46(t, J=7.4Hz, iH, -CH(CO2
CH,)).

3.73 (s, 3H, -Co2CH3), 3.99 (s
, 2H.

5iOCH2), 5.04(t, J=64Hz, IH,
C=CHCHv), 5.33(t, J=6.8Hz
, I.H.

C=CH-CH,-).

Example 4 O2Me Methyl 2-acetyl-5,9-dimethyl-10-(2-
Tetrahydropyranyl)oxy-4,8-zocadix4-
(370 mg, 1.05 mmol) in dimethyl sulfoxide solution (2 m (1)
n9.3.08 mmol) and water (0.11IIff
) and stirred at 150°C. After 4 hours, the reaction mixture was warmed to room temperature, water (15ml) was added and the product was extracted with ether (20mQ x 2). The extract is dried (anhydrous sodium sulfate), concentrated, and the resulting residue is purified by gel column chromatography to obtain 6,10-dimethyl-11-(2-tetrahydropyranyl)oxy-5,
9-Undecadien-2-one (70%) was obtained.

IR (Film) Gill'; 2950, 2880.
1720.1442, 1358.1120, 1078.
1024.905,870,815°'HNMR (CDC11,250MHz) δppm; 1
45-190(m, 6H, -OCH, -CH, -C) (
.

-CH, -CH (○)), 1.62, 1.65 (2s,
6H.

(CH3)C=CHCH2CH2(CH3)C=CH-
), 1.96-2.20 (m, 4H, -C=CH-CH
2-CH, -C=CH-), 2.14(s, 3H, C0
CH+), 2-26 (q, J-7, 1Hz, 2H, C=
CH-CH2-CH,C0-), 2.46(t, J =
7.1Hz, 2H, -CH2COCH,), 145-3
．． 55 (m, lH, 0CHa, Hb CHI CH
2CH2CH (○)), 3.84, 4.10 (2d, J
-11,5Hz.

OCH, C=CH-), 3.80-3.95 (m, I
H.

0CHaHb-CH, -CH2-CH2-), 4.60
(t.

J = 3.6 Hz, lH,CH(0)), 5.
08(t, J -71Hz, -C=CH-C)(2-
CH2-C=CH-)6.9(t, J =6.9Hz,
lH, -C=CH-CH2-CH2-C=CH-).

Example 5 O2Me Methyl 2-acetyl-5,9-dimethyl-10 (methquin methyl)oxo-4,8-decadiene (428 m
Sodium chloride (160 mg, 2°74 m
mol) and water (0.1 m+1) were added and stirred at 150°C. After 5 hours, the reaction mixture was warmed to room temperature and water (1
0+++Q) and the product was dissolved in ether (20mcx2
) was extracted. The extract is dried (anhydrous sodium sulfate), concentrated, and the resulting residue is purified by phosphoric gel column chromatography to obtain 6,10-dimethyl-11-(methoxymethyl)oxo-5,9-undecadien-2-one ( 358 mg, 67%) was obtained.

IR (film) cm-'; 2940, 1720, 14
40.1358, 1150, 1100, 1050, 92
0゜'HNMR (CDCIx, 250MHz) δppm; 1
62.1.66 (2s, 6H, 2XCH3C=CH).

1-94-2-32 (m, 6H, C=CHCH2CH2
C-CHCH2), 2.14 (S, 3H, C0CHx)
, 2-46 (tj-7, 3Hz, 2H, cH.

COCHs), 3-38 (s, 3H, CH2O
), 3.92 (s.

2H,0CH2C=CH), 4.61(S,2H,0C
HxC), 5. (18(t, J=6.1)(z, IH,
C-CHCH2), 5.40 (t, J=6.7Hz, I
H.

C-CHCH2-).

Example 6 CO□Me Hexamethylphosphoric triamide solution of methyl 2-acetyl-10-(dimethyl-butylunryl)oxy-5,9-dimethyl 4,8-decadiene monomer (96 mg, 0.25 mmol) Sodium iodide (45 u, 0.30 mmol) and water (0, OlmcL) were added to (0°5 vnQ) and stirred at 150°C.

After 2 hours, the reaction mixture was warmed to room temperature, water (2 mg) was added, and the product was extracted with ether (5 mff x 2). The extract is dried (anhydrous sodium sulfate), concentrated, and the resulting residue is purified by silica gel column chromatography to obtain 6, IO-dimethyl-11-(dimemethyl-tert-butylsilyl)oxy-undecadien-2-one C.
57rn9.70%) was obtained.

IR (film) cm-'; 2970, 2950.29
10.2g70,1725,1465.1,360.1
255.1155, 1110, 1070.837, 77
5.662゜'HNMR (CDCl2.250MH2) δppm;
0.

06(s, 6H, (CHx)zsi), 0.91(s,
9H, (CHs)scsi), 1.59, 1.62 (2
s, 6H, 2X-C-CHCH2), 1.92-2.3
2 (m, 6H.

), 2.14 (S, 3H, C0CH5), 2.46 (t
, J=8.7Hz, 2H, C flat C0CH5), 4.00
(S, 2H5iOCH,), 5.08, 5.35 (2m
, 2H, -C-CHCH2'2).

Examples 7 and 8 Methyl 2-acetyl-5,9 dimethyl- as a raw material
Examples 4 to 6 except that 10-acetoquine-4,8-decadienobutyl or methyl 2-acetyl-5,9-dimethyl-1O-(benzoyl)oxy 4,8-decadienobutyl were used. 6. By the same method. IO-dimethyl-11-
Acetoxy 5.9-undecadien-2-one and 6
．． lO dimethyl-1i (benzoyl)oxy-5,9-
Undecadien-2-one was synthesized.

Example 9 6.10-dimethyl-11-(2-tetrahydropyranyl)oxy-5,9-undecadien-2one (362
mg, 1.23 mmol) of methanol (5+IIQ
) and water (1 mQ) was added para-toluenesulfonic acid (20+ng) and stirred overnight at room temperature.

Add saturated aqueous sodium hydrogen carbonate solution (20 mff),
The product was extracted with ethyl acetate (20+n4X2). After drying the extract (anhydrous magnesium sulfate), the solvent was distilled off under reduced pressure, and the resulting residue was subjected to silica gel column chromatography to give 2,6-dimethyl-2,6-dozocadiene=1O-on-1-ol (234 mg , 90%)
was gotten.

IR (film) cm-'; 3430.2930.28
60.1715.1440.1360.1160.10
80゜' HN MR (CD CI s 1 D 20, 2
50 MHz) δppm; 1-62.1.66 (2
s, 6H, 2xCH3C=CH), 19g-2,34(
m, 6H, -C=CH-CH, -CH2-C=CH-C
H2-), 2.13 (s, 3H, C0CHi), 2,4
7(t, J=7.2Hz, 2H.

CH2C0CHs), 198 (S, 2H, CH20H)
.

5.06 (t, J=7.1Hz, lH, -C=CH-C
1(2), 5-33Q, J=6.9Hz, lH, C=C
1(-CH2-).

Example 10 H Under argon atmosphere, ketone body [6,10-dimethyl-1
1-(2-tetrahydropyranyl)oxy5.9-undecadien-2-one 1 (90 mg, Q.

A solution of 31 mmol) in tetrahydrofuran (5 shrimp) was stirred on a water bath, and lithium acetylide ethylenediamine complex (180 mg 1.95 mmol) was added thereto.
The temperature was raised to room temperature and stirred for 3 hours. A saturated aqueous ammonium chloride solution (2 mQ) was added to the reaction mixture, and the mixture was extracted with ether. After drying the extract over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting crude product was purified using silica gel column chromatography to give 3°7.11 trimethyl-12-(2-
Tetrahydropyranyl)okino 6.10-F decadien-1-yn-3-ol (75 mg, 75%) was obtained.

IR (film) cm-'; 3440.3320,29
50,2880,2200. +440.1450,13
82.1360.1260. +200.1180°11
15.1075.1020,905,865.8O'HNMR (CDCIx, 250MHz) δppm:
1.

50 (s, 3H, CH, C(OH)), 1.45-1.
90 (m, 8H, 0CH2CH: CH2CH2CH
(0), -CHzC(OH), 165(s, 6H, 2X
CHsC=CH), 2. OO~2.40 (m, 7H, C
-CHCH2CH2C=CHCH2-1○H), 2.4
6 (s, l H, -C=C-H), 3.45-3°57
(m, IH, -0CHaHb-CHx), 3.84
゜410 (2d, J = 11.5Hz, 2H, 0CH
tC=CH), 3.80-:C94(m, IH, -0C
HaHbCH2), 4.60 (t, J=3.4Hz, I
H,0CHO−), 5.19(t, J=6.7Hz, I
H, -C-CHCH2), 5.41 (t, J = 6.7
Hz, IH.

-C=CH-CH2-).

Example 11 CH Under argon atmosphere, ketone body [6,10-dimethyl=1
A tetrahydro 7 run solution (2 mQ) of 1-(methkinmethyl)oxy-5,9-undecadien-2-one] (67 mf1.0.26 mmol) was stirred on a water bath, and lithium acetylide ethylenediamine complex (30 m
g, 0.33 mmol), the temperature was raised to room temperature,
Stirred for 3 hours. A saturated aqueous ammonium chloride solution (2 volumes) was added to the reaction mixture, and the mixture was extracted with ether.

After drying the extract over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting crude product was purified using silica gel column chromatography to yield 3.7.11-1-dimethyl-12-(methoxymethyl)oxy-6. ,10-dodecadiene-1-
In-3-ol (61 mg, 83%) was obtained.

I R (7 ilm) cm-'; 3450, 3300, 2
940.1445, 1370, 1148.1045.9
18゜'HNMR (CDCl2, 250MH2) δppIIl
:l.

05(s, 3H, CHsC(0)), 1.55-1-8
4 (m.

9H,2XCdiC=CH-,OH), 2. OO～2゜4
0 (m, 6 H, C= CHCHx CH-C=
CHCHx ), 2.46 (s, IH, C=CH)
, 3°78 (S, 3H, CH30), 3-92 (5,2
H, QCH2C-CH), 4.61 (S, 2H,0CH
20), 5°19 (t, J ”6.2Hz, IH, C-
CHCHHz-).

5.41(t, J-6,2Hz, C-CHCHx
).

Example 12 CH Under argon atmosphere, ketone body [6,10-dimethyl-1
1-(dimethyl-tert-butylsilyl)oxy-
5,9-undecadien-1-one] (71 mg, 0
. A saturated aqueous ammonium chloride solution (2 ml) was added to the reaction mixture, and the mixture was extracted with ether. After drying the extract over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting crude product was purified using silica gel column chromatography. 3.7. ll-1-dimethyl-12-(dimethyl-tert-butylsilyl)oxy-6,10-dodecadien-1-yn-3-ol (51 mg, 67%) was obtained! ;.

IR (film) cm-'; 3450, 3320, 29
60.2940.2910.2860.1460.13
60.1250.1110,1065.835,775
゜' HN MR (CD Cl s, 250 MH
z) δppm; o.

06 (s, 6 H, (C1l)zsi), 0.91 (
s, 9H, (CH3)3Si), 1.50(s, 3H
, -CHz-C(OHXCH3)-C=CH), 1.5
9.1.66 (2s, 6H, 2x CHsC-CH),
l −68 to 1.76 (m, 2H.

CH2C(OH)), 1.94-2.36 (m, 7H.

C= CHCHx CH2C= CHCH20H),
2.46 (s, l H, -C=CH), 4.00 (s.

2H,0CH2-C=CH-), 5.19(L,J ~
7゜lHz, IH, C=CHCH2), 5.36 ([,
J=6.9Hz, IH, C=CHCH2) Example 13
．． 14 6.10-dimethyl-11-acetoxy-5,9-undecadien-2-one or 6,10- as a raw material
3,7.11-trinotyl-12-acetoxy-6,10-dodecadiene-1- was prepared in the same manner as in Example 11 except that dimethyl-11-(benzoyl)oxy-5,9-undecadien-2-one was used. In-3-ol and 3,7°11-trimethyl-12-(benzoyl)
Oki76, IO-dodecadien-1-yn-3-ol was synthesized.

Example 15 Example 10 except that 2,6-dimethyl-2,6-dodecadien-10-one=1-ol was used as the raw material.
2,6.10 trimethyl-2,
6-dodecadien-11-yne-1,10-diol was synthesized.

Example 16 CH Under argon atmosphere, ketone body [6,, to-dimethyl-
11-(2-tetrahydropyranyl)oxy-5,9-undecadien-2-one] (80 mg, 0°27 mmo
A tetrahydrofuran solution (3 mQ) was stirred on an ice bath, and a vinyl magnenium bromide tetrahydrofuran solution (0,3+++C, 0,3 mmol 1.l) was added to it.

After adding OM), the mixture was heated to room temperature and stirred for 10 hours.

A saturated aqueous ammonium chloride solution (2i) was added to the reaction mixture, and the mixture was extracted with ether. After drying the extract over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting crude product was purified using licage gel column chromatography to yield 3.7.11-trimethyl-12-(2tetrahydropyranyl)oxy-
1,6,10-undecatrien-3-ol (61m
g, 70%) was obtained.

IR (film) cm-'; 3460, 2950, 28
80.1200.1118, 1075.1022.90
5.865,810°'HNMR (CD CIs, 250 MHz) δpp
m; l.

28(S, 3H, C(OH)CH3), 11-65-1
-92(,8H,0CHz CH2CHx CH2
CH(0), cHx C(OH)), 1. (J5-2
．． 40 (m.

7 H, C= CHCH2CH2C= CHCH2-,
OH), 3.45-3.55 (m, IH, -0CHaH
b-CH2-), 3.84, 4.10 (2d, J=11
．． 6Hz, 2H, OCHx C-CH2), 3
-80~3.

95 (m, l H, 0CHaHb CHz), 4
-60 (t.

J=3.4Hz, IH,0CH(0)), 5.06(
dd, J-1,3, I O, 7Hz, I H, -CH=
CHaHb), 5°14(m, IH, C=CHCHx
), 5-22 (dd.

J-1-3, 17-4Hz, lH, -CH-CHaHb
).

5-41 (t, J=6-3Hz, lH, -C-CH-C
H2), 5.92 (da, J=10.7, 17.4Hz
, 1H, -CH=CH2).

Example 17 CH Under argon atmosphere, ketone body [6,10-dimethyl-1
1(methoxymethyl)oxy-5,9-undecadien-2-one] (60 mg, 0.24 mmol) in tetrahydrofuran was stirred on a water bath, and a solution of vinyl mag unsium bromide in tetrahydrofuran (1 in.) was stirred on a water bath.
,0mff, 1.0mmol, 1.0M),
The temperature was raised to room temperature and stirred for 4 hours. A saturated aqueous ammonium chloride solution (2 mQ) was added to the reaction mixture, and the mixture was extracted with Nityl. After drying the extract over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting crude product was purified using silica gel column chromatography. 3.7. ll-trimethyl-12-(
methoxymethyl)oxy-1,6,10-dodecatrien-3-ol (54 mg, 80%) was obtained.

IR (film) cm-'; 3480.29-40.1
450.1370,1210,1150.1100,1
045,920,845,685゜'HNM R (CD CI3.250 MH2) δpp
m; 1.

28 (s, 3 H, CHsCCOH)), 1.60
, l -66 (2s, 6H, 2xCH1-CH-C-
), 1.522-172(,2H,cH,C(OH))
, 1.95-2-20 (m, 7H, C-CHCH
2CH2C-CHCH2-, OH), 3.38(S, 3
H, CH30), 3°92 (s, 2H, -OCH, C=
CH-), 4.61 (s.

2H, -0CR20-), 5.06 (dd, J -1,
310.7Hz, lH, -CH=CHaHb), 5.1
4Q, J=7-2Hz, lH,C=CHCHx)
, 5.20 (dd, J -1,3,17,4Hz, IH
, -CH-CHaHb), 5.41 (t, J =
6.9 Hz, lH, -C=CHCH2), 5.9
2 (dd, J-10,7,17,4Hz.

IH, -CH=CH, -).

Example 18 Me2tB “8” shape → CH Under argon atmosphere, ketone body [6,10-dimethyl-1
1-(dimethyl-tanyarybutylunril)oxy-
5,9-undecadien-2-one] (48 mg, 0
, 15 mmol) in a tetrahydro7rane solution (2 m
Q) was stirred on a water bath, and a solution of vinylmagnesium bromide tetrahydro 7rane (1(h++Q, 1.0 mm
After adding 1,0 M), the temperature was raised to room temperature,
Stirred for 4 hours. A saturated aqueous ammonium chloride solution (2 mQ) was added to the reaction mixture, and the mixture was extracted with ether. After drying the extract over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting crude product was purified by gel column chromatography. Silyl)oxy-1,6,10-dodecatrien-3-ol (32 mg, 60%) was obtained.

IR (film) cm-'; 3420, 2970, 29
40.2860, 1462.1360.1250.11
50.1070.920,835,775,662゜'
HNMR (CD CIs, 250 MHz) δppm
; 0.

06(s, 6H, (CHs)zsi), 0-91(s,
9H, (C)(x)scsi), 1.28(s, 3H,
C(OHXCH3)-CH誼CH2), 1.60(S,
6H,2XCH3C=CH), 1-46~l-73(
m, 3H, CHtC(OHXCH=)) -14,00
(s, 2H, S+OCH2).

5.06 (dd, J-1, 3, 10, 7Hz, IH, -
CH=CHaHb), 5.14(m, lH, -C-CH
-CH.

), 5.22 (dd, J-1, 3, 17, 4Hz, lH
.

CH=CHaHb), 5.36(m, lH, -C=CH
CH2), 5.92 (dd, J=IO, 7, 17, 4H
z.

l H, -CH= CHx -) Example 19 6. as a raw material. lO-dimethyl-11-acetoxy-5,9-undecadien-2-one or 6. lO-
3,7.11-trimethyl-12-acetoxy-1,6,10-undecadien-2-one was prepared in the same manner as in Example 16 except that dimethyl-11-(benzoyl)oxy-5,9-undecadien-2-one was used Trien-3-one and 3
,7.11trimethyl-12-(benzoyl)oxy-
1,6°10-undecatrien-3-one was synthesized.

Example 20 Example 17 except that 2,6-dimethyl-2,6-dozocadien-lO-one-1-ol was used as the raw material.
Same method as 18! From this, 2,6,10-trimethyl-2,6,11-dodecatriene 1,10-diol was synthesized.

CH3,7,11-)limethyl-12-(methoxymethyl)
Oxy-6,lO-dodecadien-1-yn-3-ol (175++g, 0.62 mmol), tris(triphenylsilyl)vanadate (49 mg, 0.062
mmol), and benzoic acid (7.6 mg, 0.0
62 mmol) xylene solution (2 mQ) at 140°C
The mixture was stirred on an oil bath. After 2 hours, return to room temperature and add hexane (
15 mff) was added thereto, and insoluble materials were filtered off. The filtrate was concentrated under reduced pressure, and the residue was subjected to licage gel column chromatography to yield 12(methquinmethyl)oxy7-3.7,111-limethyl-2,6,10-dodecatrienal (88 mg).

50%) was obtained.

IR (film) cm”; 2950, 1675, 145
0.1385.119-8.1157,1120.11
05.1050,925,850゜'HNMR (CDCl2, 250MH2) δppm;
1.

57.1.62.2.13 (each s, each 3H, CH,
C=CH-), 1.93-2.30 (m 8H, 2x-
C=CH-CHi-CH2-), 3.33(S, 3H,
CH30).

3.88 (s, 2H, -QCdanyuC=CH-), 4.5
7(s, 2H, -0CH20-), 5.06, 5.36
(Each m.

I H, -C=CH-CH2), 5-84 (d, J
-8,2Hz, IH, -C-CH-CHO), 9.9
6 (d, J=8.2Hz, IH, -C=CH-CHO)
.

Reference Example 2 3.7.11-trimethyl-12-(methoxymethyl)oxy-1,6,10-dodecatrien-3ol (
460 mg, 1.6 mmol) in dichloromethane solution (30+xff) of pyridinium chlorochromate 69
0 m9c 3 , 2 mmol) was added and stirred vigorously at room temperature for 8 hours. Hexane-ethyl acetate-ether (3:1:1, 100 mQ) was added to the reaction solution and stirred.
Thereafter, insoluble matter was filtered off. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography to give 12
-(methoxymethyl)oxy-3,7,11 trimethyl-2,6,10-dodecatrienal (233 mg, 5
2%) was obtained.

The physical property values are the same as those described in Reference Example 1.

Reference Example 3 Under an argon atmosphere, a 1.0 M hexane solution of lithium bis(trimethylsilyl)amide (1.3 mQ, 1 3 mmo+) was added dropwise while stirring at -70°C. 30
After a few minutes, at the same temperature, formyl compound (12-(methoxymethyl)
Okin 3.7. l l -trimethyl-2,6°IO
-Dodecatrienal XI 30rng, 0.46mm
A toluene solution (2 mQ') of o1) was added, and the temperature was raised to room temperature over about 3 hours. An aqueous ammonium chloride solution (6 mQ) was added to the reaction solution, and the product was extracted with hexane.

The extract was dried (after anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting residue was subjected to silica gel column chromatography (developing solution: n-hexane: ethyl acetate = 201) to obtain the nitrile compound (2-(1- methylethyl)-1
4-(Methquinmethyl)oxy-5,'1,13-trimethyl-2,4,8,12-tetraenenitrile) (
135 mg, 85%) was obtained.

00.2310,1640.1150.1050゜'N
NMR (CDCl2, 250MH2) δppm;
1.

17(d, J = 6.8 H2,6H, (CH3)
2CH-), l.

61.1.67.1.84 (each S, each 3H, CHyuC=CH-), 1.96-2.21 (m, 8 H, -
C=CH-CHl-C dani C=CH-C mon ni C dani), 2°53 (hel), J=6.8Hz, IH, C
H(CH3)ri.

3-38 (S, 3H, CH30), 3-92 (S, 2H
, -0CH20), 4.62(s, 2H, OCHz
C-CH), 5.10 (brs, IH, -C=CH-)
, 5°42 (brt, J=6.4Hz, lH, -C=C
H-), 6°28.6.82 (respectively d, J = 11.
5Hz, each IH.

C=CH-CH=C (CN:l-).

Reference Example 4 Add a small amount of concentrated hydrochloric acid to a methanol solution (5 mQ) of the nitrile compound (135 mg, 0.39 mmol), and heat at 60°C.
IR (film) am-'; 2980.2945.29
and stirred for about 6 hours. Add a saturated aqueous solution of sodium bicarbonate (20+++Q) and dilute with ether (20 mO
2). After drying the extract (anhydrous magnesium sulfate), the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solution: n-hexane:ether = 5:l) to obtain a hydroxynitrile compound (9 -6 mg, 82%) was obtained.

IR (film) cm-'; 3460, 2980, 29
30.2210.1635.1450.1020゜Vine H
NMR (CDCls, 250 MHz) δp
pm; t.

14 (dJ-6,8Hz, 6H, (CHs)zCH),
11-58(,4H,CH,C=CH-,-0H), 1
．． 65 (S, 3H, CH3C=CH), l-81 (d,
J=1. IHz, 3H, CHxC-CH), 1-92
2.25 (m.

8 H, C= CHCH: CH2(CHs) C
= CH-CH, -C-), 2.51 (hep, J-
6.8Hz.

lH, (CH,)=CH-), 3.97 (d, J=5.
9Hz.

2H, CH, OH), 5.08 (brs, lH, -C=
C), 5.36 (m, LH, -C=CH-), 6.2
6.6°80 (each d, J = 11.5Hz, each
IH, -C=CH-CH-C(CN, )).

Reference Example 5 Hydroxynitrile compound (130 mg, 0.43 mmol
) in a toluene solution (5 mQ) under an argon atmosphere.
A 1M toluene solution (2.0 m4, 2.0 mmol) of diimbutylaluminum hydride was gradually added dropwise at 0°C. After stirring at -70°C for 2 hours, 1M oxalic acid aqueous solution (4,
0m+2) was added thereto, and the temperature was slowly raised to room temperature while stirring under an argon atmosphere. Wash the organic layer with water, wash with saturated aqueous sodium bicarbonate solution, and dry (anhydrous sodium sulfate).
Afterwards, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel chromatography (developing solution: n-hexane:ethyl acetate = 7:I).
The desired hydroxyformyl compound (11Jmy
, 85%) was obtained.

IR (film) cm-'; 3430, 2960, 29
20.2870, 16701630, 1450.139
0.1295.1230, 1130.1070°101
0°'HNMR (CDCl2, 250MH2) δppm;
1-04(d, 6H, J=6.8Hz, -CH(CHs
)z), l-59(d, JO-6Hz, 3H, CHx
C=), L63(brs, 3H, CH, -C=), 1
,．． 86 (d, J=1.2Hz, 3H, CHs-C=)
, 1.7-2.2 (m, 8H.

CH2CH2-), 2.88 (hepJ-6,8Hz,
lH.

CH(CH3)z), 3-95(brs, 2H, -CH
xOH).

5.09 (m, IH, -C) f, CH-), 5.38 (
brt, J-6, 8Hz, IH, CHxCH-), f3
-80Cd, J= 12.0Hz, 2H, =CH-CH
=), 7.11 (d.

J=12.0Hz, IH,=CH-CH-), 10.2
5(s, lH, -CHO).

Reference Example 6 Dry lithium chloride (64 mg, 1.5 mmol),
2゜6-lutidine (0,23+IIQ, 2-Omr++
ol), and hydroxyformyl (305+ig,
1.0 mmol) of dimethylformamide (1.0 i
12) Cool the solution on ice water and add methanesulfonyl chloride (160 mg, l) while stirring under an argon atmosphere.
, 4 fights. 1) was added.

After about 8 hours, disappearance of the raw material was confirmed, and the entire solution was dissolved in water and ether. The organic layer was washed with water, dried (MgSO4), and concentrated, and the resulting residue was purified by 5i03 column chromatography (developing solution, n-hexane: ethyl acetate 15:1) to obtain the desired chloroformyl compound (281 mg, 87 %) was obtained.

IR (film) cm-'; 2970.2930.28
80.1670.1630, 1445.1390.12
95.1265, 1135°NMR (CDCl2.250MH2) δppm; l
,04(d,J-7,0Hz,6H,-CH(CH3)
2,1.59゜1.70 (each bs, each +3H, -
C=CCdan,), 1.

87 (d, J=1.3Hz, 3H, -C=CCH,),
1゜9 2.2 (m, 8H, CH2CH2), 2689
(hep.

Jx7.0Hz, lH, CH(CHs)z), 3.98
(bs.

2H, CHzCl), 55-09(, IH, C=CHC
Hx), 5.47 (bt, J-6, 5Hz, IH,
c-cHCH2), 6.82 (d, J=12.0Hz,
IH.

C=CH-CH=C(CHO)-), 7.11(dj=
12.0 Hz, -C=CH-CH=C(CHO)-).

10.27 (s, IH, -CHO).

Reference Example 7 CHo formyl compound (14-chloro-2-(1-methylethyl)
-5,9,13-1-limethyl 2.4,8.12tetradecatetraenal, 640 mg, 2.0 mm.

Q) to trimethylsilylnitrile (0,35+++<1
．． A very small amount of potassium cyanide/18-
Crown-6-ether complex was added. After 2 hours, the disappearance of the raw material was confirmed, and excess trimethylsilylnitrile was distilled off to give crude 15-chloro-3-(l-methylethyl)-6,
10,14-trimethyl-2-(trimethyl70quin)
3,5.9.13-pentadecatetraenenitrile C6
47 mg (quantitative) was obtained.

rR (film) cm-'; 2960.2930.28
80.2320, 1445.1255. l080,87
5.845'HNMRCCDCQs, 250MHz) δppm; 1
．． 11.1.15 (each d, J=6.9Hz, each 3
H,-CH(CH,),), 1.60.1.71,1.
77 (each s, each 3H, C=CCH3), 1.9 2
．． 2 (m, 8H.

CH2CH2), 2.64 (hep, J=6.9Hz,
IH.

C (CH3)2), 3.99 (S, lH, -CHzC
ff).

5, l l(m, IH, C=CHCH2), 5.33(
S.

IH, -CdanCN), 5.48 (bt, J-6,5Hz
, IH, -C=CHCH2-), 6.04, 6.25 (
Each d.

J-11, 3Hz, each hlH, -C=CH-CH=C)
.

Reference Example 8 Under an argon atmosphere, a tetrahydrofuran solution of lithium hexamethyldisilazide (20mQ, 5.QOmmoQ
, 0, 25 M) was stirred on an oil bath at 55°C, and 15-chloro-3-(l-methylethyl) 6.10
．． 14-) riftyl-2-trimethylsiloquine 3,5,
9.13-pentadecatetraenenitrile (G'X37
A solution of 8 mL (0.895 mmof2) in tetrahydrofuran (15 m+2) was added dropwise over 50 minutes. After stirring at this temperature for 20 minutes, the reaction solution was mixed with ice (50 g) in saturated brine (30+++Q)-hexane (20+11+
1) Pour into the mixture to stop the reaction. After separating the organic layer,
The aqueous layer was diluted with hexane-ether (5:1).

30 mff). Dry the extract (Na2So,
) L, the residue obtained after removing the solvent under reduced pressure? When purified by silica gel column chromatography, 2-(l-methylethyl)-5,9,13-trimethyl-1-1-limethylronroxy2.4.8.12-cyclotetradecatetrax-1-carbonitrile (H'X288mg .

83%) and 2-(1-methylethyl)-5,9,13-
Trimethyl 2,4.8.12-cyclotetradecatetraen-1-one (JX42.9mg, 0.11mmoQ
, 16%) was obtained.

The physical properties of compound (H') are as follows.

IR (film) cm-'; 2970.2920.14
40.1385.1253.1125. l 085,9
40.845,755°'HNMR (CD CQs, 250 MHz) δpp
m; 0, 23 (s, 9H, SiMex), 1.09
．． 115 (each d.

J”6.7Hz, each h3H, CH(CH3),
l, 50.1.62 (each bs, each 'r3H, C-
CCHs), 1-70 (d, J=1.3Hz, 3H, C
=CCH3), 2-0 2.2(m, 8H, CH2CH
2X2), 2.51 (sep, J = 6.7Hz, l
H, -CH(CH3)2), 2.55.2.65 (d each, J = 14.2 Hz, IH each.

CHaHbCN-), 4.94 (bt, J = 6.1
Hz, IH.

-C=CdanCHz), 5.15 (btj =5.6
Hz, LH, -C=CHCH2-), 6.17.6.4
4 (each d.

J=I1.8Hz, each lH, -C=CH-CH=C)
.

Reference Example 9 1.0M) was added. After stirring the reaction solution at room temperature for 17 hours, saturated brine (10 ml) was added, and the organic matter was extracted with hexane-ether (5:1.30ii+x2). After drying the extract (Na2so+), the solvent is distilled off under reduced pressure to obtain the desired 1-(1-methylethyl)-5,9,
13-trimethyl 2.4.8.12-cyclotetraen-1-one (200ml, 9.94%) was obtained.

2-(ltrimethylethyl)-5, under argon atmosphere
9,13-)limethyl=1-trimethylronroxy2,4
．． 8.12-N Clotetrade Force A solution of tetraene-I-carbonitrile (288 mg 0.74 mmol) in tetrahydrofuran (lomQ), water (0°3 ml') and tetrabutylammonium fluoride in tetrahydrofuran solution (16 μθ, 0.016 mmol).

Under argon atmosphere, ketone body (2-(1-methylethyl)-5,9,13-)limethyl 2,4,8.12 cyclotetradecatetraen-1-one, 137 yny,
0,48 mmo(i) of dry toluene 2,5rnQ
Add diisobutylaluminum hydride in 1M toluene HO, 6 mQ to the solution while stirring on a -70°C refrigerant bath.
was dripped. After 1 hour, the disappearance of the raw material was confirmed, and 0.25
Add No. 2 water, remove the bath and stir well.

After drying over anhydrous magnesium sulfate, stirring, filtering, and concentrating, the resulting residue was subjected to silica gel column chromatography (
Purified with developing solvent, n-hexane:ethyl acetate = 12:1) to obtain the desired sarcotuitol A (125 mg,
88%) was obtained.

(Effect of the invention) The compound of the present invention has an anti-carcinogenic bromomotor effect and an anti-tumor effect.
It is extremely useful as a synthetic intermediate for sarcotuitol A, which has one effect.

Claims (1)

[Claims] (1) The following general formula (I) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R^1 is a hydrogen atom, a 1-alkoxyalkyl group, a tetrahydropyranyl group, a tetrahydrofuranyl group,
There are acyl groups, or ▲mathematical formulas, chemical formulas, tables, etc.▼(
In the formula, R^3, R^4, and R^5 each independently represent an alkyl group or phenyl group having 1 to 10 carbon atoms, and R^2 has a ▲ mathematical formula, chemical formula, table, etc. ▼ [In the formula, R^6 is a hydrogen atom or -CO_2R^7 (in the formula, R
^7 represents an alkyl group having 1 to 4 carbon atoms. However, R^
When 1 represents a hydrogen atom, R^6 does not represent a hydrogen atom, and when R^1 represents a 1-ethoxyethyl group, R^7 does not represent a methyl group)] or ▲ Formula, There are chemical formulas, tables, etc. ▼ (In the formula, R^8 is -
C≡C-H or -C=CH_2} A chain terpene compound represented by: