JPH04352781A - Cyclic ethers - Google Patents

Abstract

PURPOSE:To provide the subject new compound useful as an intermediate for the production of sarcophytol A having antitumor promoter action and antitumor action. CONSTITUTION:The compound of formula I [R is CH2C=CH-CH=CCH(CH3)2 (each double bond has Z or E steric configuration); * represents asymmetric carbon atom]. The compound of formula I can be produced by adding trichloromethanesulfonic acid to a n-hexane solution of monotrichloromethylimidate of formula II in argon atmosphere, neutralizing with triethylamine, distilling off the solvent under reduced pressure and purifying the product by SiO2 column chromatography.

Description

[Detailed description of the invention]

0001

TECHNICAL FIELD This invention relates to novel cyclic ethers. Specifically, the compounds of the present invention exhibit anti-carcinogenic promoter activity (Cancer Surveys, 2
, 540 (1983); Metabolism, vol25 special issue
Cancer '88, 3 (1988). ) and antitumor activity (Japanese Patent Publication No. Sho 63-20213), this invention relates to cyclic ethers that are important intermediates for the production of Sarcophytol A or its stereoisomers that are expected to have similar effects.

0002

BACKGROUND OF THE INVENTION Sarcophytol A represented by the following structural formula is a Semblan-type diterpene alcohol having a total of four double bonds, including one conjugated double bond, in its 14-membered ring.

[Case 2]

[0003] Up to now, the only method for synthesizing sarcophytol A has been reported by the present inventors (
Patent Application No. 3-48633; Tetrahedon
(See Letters, 31, 3317 (1990)). When trying to industrially produce sarcophytol A using this production route, 1) the yield and selectivity are not high, and a highly toxic selenium compound must be used. There were two major problems: the oxidation step of the group cannot be avoided, and 2) when considering the production of optically active sarcophytol A, the final stage involves an asymmetric reduction step in which the reaction is carried out at an extremely low temperature. .

0004

[Problems to be Solved by the Invention] As a result of intensive studies aimed at producing and supplying sarcophytol A or its stereoisomers in large quantities and at low cost by an industrially more advantageous method, the present inventors have discovered the present invention. The inventors have discovered that the cyclic ethers of the invention are useful intermediates in a new production route that can solve the above problems, and have arrived at the present invention. That is, the gist of the present invention is that the following general formula (I)

embedded image represents the configuration of Z or E. ) and * represents an asymmetric carbon atom).

The present invention will be explained in detail below. In the general formula (I), the configuration of the two double bonds of R is 1)
E E2) E
Z3) ZE
4) Four types of ZZ are possible, and the asymmetric carbon atom indicated by * represents S, R, or racemic.

Specific examples of preferred compounds represented by formula (I) are shown below.

[C4]

[C5]

[C6]

[Chemical 7]

[Chemical formula 8]

[Chemical formula 9]

Next, the method for producing the compound of the present invention will be explained. The compound represented by general formula (I) can be produced, for example, from a linear precursor represented by general formula (I'), diolimidate or phosphate (the manufacturing method will be described later).

[Chemical formula 10] (wherein, R is as defined above, and X represents a fluorine atom or a chlorine atom)

That is, from the compound represented by the general formula (I'), hydrocarbon solvents such as n-pentane, n-hexane and toluene, ether solvents such as diethyl ether and tetrahydrofuran, and halogen solvents such as methylene chloride and chloroform are used. in a solvent such as a solvent at -100 to 50°C.
A compound represented by general formula (I) is prepared by a method such as allowing an acid catalyst such as 01 to 2 equivalents of trifluoroborane-diethyl ether complex, trimethylsilyl trifluorosulfonate, or trifluoromethylsulfonic acid to react for 5 minutes to 5 hours. Can be manufactured.

[0009] In this reaction, when a hydrocarbon solvent is used as a reaction solvent, a compound (I) in which the geometric isomerism of the conjugated diene moiety in compound (I') is maintained is obtained, but an ether solvent When using isomerization, compound (I) with opposite stereochemistry can be obtained, and it is possible to produce and separate two types of compound (I) from the same compound (I'). be. The compound represented by general formula (I') can be produced from monoterpenoid, geranial or neral (compound (A)) or sesquiterpenoid (6E)-fanesal (compound (F)) according to synthetic routes -1 or -2, respectively. It can be produced via Compound (E) or Compound (K).

0010

[Chemical formula 11]

embedded image where R is as defined above and R1 is -CO2
R2 (R2 represents an alkyl group having 1 to 5 carbon atoms), a cyano group, a formyl group)

That is, the above compound (B) or (G)
is, for example, 0.1 to 10 equivalents of 2-(dimethylphosphono)- from each compound (A) or compound (F).
Wittig-Horner reagents such as isovaleronitrile, 2-(diethylphosphono)-isovaleronitrile, and ethyl 2-(diethylphosphono)-isovalerate, ether solvents such as tetrahydrofuran and diethyl ether, toluene, n-hexane, etc. In a hydrocarbon solvent or an aprotic polar solvent such as dimethylformamide or dimethyl sulfoxide at -100 to 100°C, a metal such as sodium hydride or potassium hydride in an amount of 1 equivalent or less relative to the Wittig-Horner reagent as a base. A method of treatment at a temperature of -100 to 100°C with an anion generated by the action of a hydride, an organic metal such as n-butyllithium or lithium diisopropylamide, or a metal alkoxide such as sodium methoxide or t-butoxypotassium; or

[Chemical formula 13]

A phosphorane compound such as [Chemical formula 14] is mixed in a halogen solvent such as methylene chloride or chloroform, an ether solvent such as diethyl ether or tetrahydrofuran, or an alcohol solvent such as methanol or ethanol at -50 to 100°C for 5 minutes to Compounds in which R1 is represented by a cyano group or -CO2R2 are obtained by a method in which R1 acts for 24 hours, and these are further treated in a hydrocarbon solvent such as n-hexane, heptane, benzene, or toluene at -100 to 150°C for 0.1 ~
R by a method of reacting with 10 equivalents of metal hydride such as diisobutylaluminum hydride and then hydrolyzing.
Compounds in which 1 is a formyl group can be produced.

From the compound (B) or (G) produced by the above method, in a halogen solvent such as methylene chloride or chloroform, an ester solvent such as ethyl acetate or methyl acetate, or an ether solvent such as diethyl ether or tetrahydrofuran, A method in which 0.1 to 10 equivalents of an organic peracid such as peracetic acid or metachloroperbenzoic acid is reacted at -50 to 100°C, or a method in which 0.1 to 10 equivalents of N-bromosuccinic acid is reacted with aqueous tetrahydrofuran, dioxane, etc. as a solvent. A method in which N-halocarboxylic acid amides such as imide, N-chlorosuccinimide, and N-bromoacetamide are allowed to react at -20 to 100°C for 5 minutes to 5 hours, and then reacted with a base such as sodium carbonate or potassium carbonate; Alternatively, each compound (C) or (H) can be produced by epoxidation by a method in which hydrogen peroxide is applied in an organic nitrile solvent such as acetonitrile or benzonitrile.

Compound (C) or (H) is treated with 0.1 to 10 equivalents of aluminum alkoxide such as aluminum triisopropoxide at 0 to 150°C in a hydrocarbon solvent such as toluene, xylene, or ligroin. or in a solvent such as diethyl ether or tetrahydrofuran at -100 to 100°C, from 0.1 to
Compound (D) or (K) can be produced by a method in which 10 equivalents of metal amides such as lithium diethylamide and lithium diisopropylamide are reacted with each other. From compound (D), for example, 0.1 to 50 equivalents of 3,3
-dimethoxy-2-methyl-2-butanol without a solvent or in a solvent such as toluene, xylene, quinoline, etc.
01 to 5 equivalents of mineral acids such as sulfuric acid and phosphoric acid, and organic acids such as 2,4-dinitrophenol, oxalic acid, and o-nitrobenzoic acid, while distilling off the methanol produced.
Clais to act for 5 minutes to 10 hours at 0 to 250℃
It can be converted to compound (E) by en rearrangement or the like. From compound (H), compound (J) is obtained by, for example, reacting a catalytic amount of a strong acid such as perchloric acid or sulfuric acid in a water-containing solvent such as tetrahydrofuran or dioxane at -10 to 50°C for 5 minutes to 24 hours. can be manufactured. This compound (
From J), for example, a complex formed by reacting N-chlorosuccinimide, oxalyl chloride, etc. with a sulfide compound such as dimethyl sulfide in a solvent such as toluene or tetrahydrofuran is used, for example, in a solvent such as toluene or tetrahydrofuran.
The same compound (E) as obtained by the above-mentioned method can be prepared by subjecting it to so-called Swern oxidation, which is reacted for 10 minutes to 5 hours at .degree.

From the compound (E) obtained by the above method, for example, in a water-containing ethanol solution in which D-glucose is dissolved,
with baker's yeast for 1 to 10 hours, preferably for 2 to 3 days.
A compound (I') having an absolute configuration of R and S as shown below, using an optically active α-diol compound (L) as a starting material, which can be produced by stirring at 10 to 40°C, preferably 20 to 30°C. can be manufactured and divided.

[0015]

[Chemical formula 15]

[Image Omitted] (wherein R, R1, and X are as defined above, and R3
represents an alkyl group having 1 to 5 carbon atoms which may be substituted with a halogen atom or a phenyl group which may have a substituent)

[Image Omitted] (wherein, R, R1, and X are as defined above, and R4
represents an acyl group)

That is, from compound (L), for example, 0
．． 1 to 100 equivalents of triethylamine, pyridine, N,
In the presence of an organic base such as N-dimethylaniline, in a solvent such as a halogen solvent such as methylene chloride or chloroform, an ether solvent such as diethyl ether or tetrahydrofuran, or a hydrocarbon solvent such as n-hexane, benzene or toluene, Alternatively, without using a solvent and using an organic base as a solvent, 0.1 to 100 equivalents of methanesulfonyl chloride, p
- Sulfonyl halides such as toluenesulfonyl chloride, or sulfonic acid anhydrides such as trichlorosulfonic anhydride and p-toluenesulfonic anhydride, from -50 to 10
Compound (M) is obtained by a method of reacting at 0°C for 5 minutes to 50 hours, and then 0.1 to 100 equivalents of sodium hydroxide, in an organic solvent such as methanol, ethanol, acetone, tetrahydrofuran, toluene, or in water. Sodium carbonate, potassium carbonate, sodium methoxide,
Add a base such as sodium hydride to -50 to 100℃ for 5 minutes.
Compound (N) can be produced by a method such as allowing it to react for 10 hours. A method in which compound (N) is reacted with 0.1 to 10 equivalents of aluminum alkoxide such as aluminum triisopropoxide in a hydrocarbon solvent such as toluene, xylene, or ligroin at 0 to 150°C, or diethyl ether or tetrahydrofuran. Compound (O) is prepared by reacting 0.1 to 10 equivalents of metal amides such as lithium diethylamide and lithium diisopropylamide at -100 to 100°C in a solvent such as
can be manufactured. From compound (O), when R1 is a formyl group, in a solvent such as methanol or ethanol, 0.1
~10 equivalents of a reducing agent such as sodium borohydride or sodium cyanoborohydride at -80 to 100°C for 5 minutes ~
By a method of reacting for 5 hours, etc., R1 becomes -CO2R2
diethyl ether, tetrahydrofuran,
Metal hydrides such as dibutylaluminum hydride, metals such as sodium aluminum hydride at -100 to 50°C in ether solvents such as dimethoxyethane, hydrocarbon solvents such as benzene, toluene, n-hexane, n-heptane, etc. When R1 is a cyano group, a method such as allowing 0.1 to 10 equivalents of a complex compound to react for 5 minutes to 5 hours is applied to - in a hydrocarbon solvent such as benzene, toluene, n-hexane, or n-heptane. 0.1 to 10 equivalents of a metal hydride such as dibutylaluminum hydride at 100 to 50°C for 5 to 5 minutes.
After being allowed to react for a period of time, it is hydrolyzed to form a compound in which R1 is formyl, and subjected to the same reaction as above to produce compound (P).

From compound (P), for example, 0.01 to 5 equivalents of sodium hydride, potassium hydride, etc. are dissolved in an ether solvent such as diethyl ether or tetrahydrofuran, or a polar aprotic solvent such as dimethylformamide or dimethyl sulfoxide. , -50 to 50°C for 30 minutes to 5 hours, and then 0.1 to 1 equivalent of trichloroacetonitrile or diphenylphosphorochloridate can be reacted to produce S-compound (I').

Further, in the presence of 0.1 to 10 equivalents of a base such as triethylamine or pyridine, 0.0.
1 to 10 equivalents of an acyl halide such as acetyl chloride or benzoyl chloride or an acid anhydride such as acetic anhydride in a halogen solvent such as dichloromethane, an ether solvent such as diethyl ether, or a hydrocarbon solvent such as benzene or n-hexane. medium, or using a base as a solvent without using a solvent, -
Compounds (
Q) can be manufactured. From compound (Q), for example 1 to 1
In the presence of 00 equivalents of an organic base such as triethylamine, pyridine, N,N-dimethylaniline, etc., halogenated solvents such as methylene chloride and chloroform, ethereal solvents such as diethyl ether and tetrahydrofuran, n-hexane,
In a solvent such as a hydrocarbon solvent such as benzene or toluene, or without using an organic base as a solvent, 0.1
Compound (R) can be produced by a method in which ~1 equivalent of phosphorus oxychloride, thionyl chloride, or the like is reacted.

-1 from compound (R) in a hydrocarbon solvent such as n-hexane, heptane, benzene, toluene, etc.
0.1 to 10 equivalents of a metal hydride such as diisobutylaluminum hydride is reacted at 00 to 150°C, and when R1 is a cyano group, hydrolysis and reduction are carried out in the same manner as in the production of compound (P) above. Compound (S) can be produced by a method of carrying out the following steps and then hydrolyzing the compound. Compound (S) to R
-Compound (I') can be produced in the same manner as in the production of S-Compound (I') from Compound (P) described above. Further, the compound represented by the general formula (I') includes monoterpenoids,
Synthetic route-3 or - from geraniol or nerol (compound (A')) or sesquiterpenoid, (6E)-farnesol (compound (F')), respectively
Since it can be manufactured according to 4, it can also be manufactured from (E').

[0020]

[Chemical formula 18]

embedded image (wherein, R5 is a 1-alkoxyalkyl group, 2-tetrahydropyranyl group, 2-tetrahydrofuranyl group,

[Chemical formula 20] (R6, R7 and R8 each independently have 1 to 1 carbon atoms
5) represents an alkyl group or phenyl group), represents an acyl group)

That is, compound (A') or (F')
to chloromethyl-2-methoxyethyl ether etc.
- Haloalkyl ethers in halogenated solvents such as methylene chloride and chloroform, ethereal solvents such as diethyl ether and tetrahydrofuran, or solvents such as ethyl acetate and dimethylformamide, or in the absence of a solvent, from 0.5 to 1
-20 using 0 equivalent of metal hydride such as sodium hydride, potassium hydride, amines such as triethylamine, diisopropylethylamine, or pyridine as a base.
〜+100℃ for 5 minutes to 24 hours,
Alternatively, 0.1 to 10 equivalents of vinyl ethers such as ethyl vinyl ether and dihydropyran are mixed with a catalytic amount of mineral acids such as hydrochloric acid and sulfuric acid, organic sulfonic acids such as para-toluenesulfonic acid and camphorsulfonic acid, or pyridinium salts of para-toluenesulfonic acid. The reaction is carried out at -20 to +100°C in the presence of a salt of a strong acid such as, in a halogenated solvent such as dichloromethane or chloroform, an ether solvent such as diethyl ether or tetrahydrofuran, or a solvent such as ethyl acetate or dimethylformamide, or in the absence of a solvent. Alternatively, 0.1 to 10 equivalents of halogenated trialkylsilane such as trimethylsilyl chloride or dimethyltert-butylsilyl chloride may be added to a halogenated solvent such as methylene chloride or chloroform, a hydrocarbon solvent such as hexane or benzene, or diethyl ether. , ethereal solvents such as tetrahydrofuran or ethyl acetate, dimethylformamide,
-20~+ using 0.1~10 equivalents of a nitrogen-containing compound such as triethylamine, dimethylaminopyridine, imidazole, or a metal hydride such as sodium hydride or potassium hydride as a base in a solvent such as dimethyl sulfoxide.
A method of reacting together at 100°C for 5 minutes to 24 hours, or 0.1 to 10 equivalents of an acyl halide such as acetyl chloride, benzoyl chloride, or acetic anhydride in the presence of a base such as 0.1 to 10 equivalents of triethylamine or pyridine. acid anhydrides such as in 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, -20 ~ Compound (B') or (G') can be produced respectively by a method of reacting at +100°C. Then, to compound (B') or (G'),
Compound (E') can be produced by performing the same series of reactions as those for deriving compound (E) from compound (B) or (G), respectively, described above. Furthermore, compound (L') can be produced by subjecting compound (F') to the same reaction as in the production of compound (L) from compound (F) described above.

[0022]

[Chemical Formula 21] From the compound (L') obtained in this way, a compound represented by the general formula (I') having the absolute configuration of R and S is converted to the compound (O) and (R) respectively. It can be produced using the synthetic route below.

[0023]

[Chemical formula 22] (In the formula, R, R1, R3, and R5 are as defined above, and R6 represents the same group as R5, but does not represent the same group at the same time)

[0024]

[Chemical formula 23] (In the formula, R, R1, R4, and R5 are as defined above, but R5 does not represent an acyl group)

That is, compounds (O') and (R') are obtained by subjecting compound (L') to the same series of reactions as those for producing compounds (O) and (R) from compound (L) described above. can be obtained. In addition, when subjecting the compound (M') in which R5 is an acyl group to an epoxidation reaction,
Depending on the conditions, R5 is removed, but as shown in the formula below, R
A series similar to the remaining compounds in 5.

[Chemical formula 24] The acylation reaction in the method for producing compound (B') from compound (A') from a diol compound (O'') capable of carrying out the reaction is carried out using an equivalent of 1 equivalent or less of the acylating agent. The compound (O') obtained by either method can be converted into the compound (O') by one of the reactions used in the production of the compound (B') from the aforementioned compound (A'). Compound (V) can be produced by subjecting it to any of the following reactions, and R5 of the two hydroxyl protecting groups in compound (V) is reacted in a catalytic amount to
A method of transesterification in which 2 equivalents of metal alkoxide is reacted at -50 to 50°C, and an aqueous solution of 0.5 to 10 equivalents of sodium hydroxide, potassium hydroxide, etc. in a solvent such as methanol, ethanol, tetrahydrofuran, etc. 50
A method of hydrolysis at ℃, in a solvent such as hydrous tetrahydrofuran or methanol, a mineral acid such as 0.1 to 12 N hydrochloric acid or sulfuric acid, a strong organic acid such as para-toluenesulfonic acid, or a pyridinium salt of para-toluenesulfonic acid. etc. at 0°C to room temperature for 5 minutes to 5 hours, or 0.1 to 5 equivalents of tetraalkyl ammonium fluoride such as tetra n-butylammonium fluoride in a solvent such as tetrahydrofuran at 0°C to 50°C. The compound (W) can be selectively removed by subjecting it to a method of acting on the compound (W).

On the other hand, the compound (R') is converted into the above-mentioned compound (
Compound (S') can be obtained by subjecting O') to any method of hydrolyzing acyl groups other than those used in the production of (V).

Compound (W) and compound (S) obtained here
') in a halogenated solvent such as methylene chloride or chloroform, a hydrocarbon solvent such as hexane or heptane, or a solvent such as ethyl ether or ethyl acetate at a weight ratio of 5 to 20%.
Compound (X) and compound (S") can be produced respectively by a method in which oxidizing agents such as powdered manganese dioxide or barium manganate are reacted at -50 to 50°C for 1 to 50 hours, and further, Compound (Y) and compound (R) can each be produced by applying the method used in the production of compound (B) from compound (A). From compound (Y), the above-mentioned compound ( Using any of the methods for producing compound (W) from V), compound (O
) can be manufactured. S- and R-compounds (I') can be produced from compound (O) and compound (R) in the same manner as described above.

Racemic compound (I') can be produced in the same manner as the above-mentioned production of S- or R-compound (I) from compound (K), compound (O) or compound (R). From compound (I') to compound (I) which is a compound of the present invention
The manufacture has already been mentioned.

From the compound of the present invention, for example, in an ether solvent such as diethyl ether or tetrahydrofuran, a hydrocarbon solvent such as benzene, toluene, or n-hexane, or a solvent system in which hexamethylphosphotriamide or the like is added to these solvents, - At 100-100°C, 0.1-10 equivalents of n-butyllithium, sec-butyllithium, te
R, S, and racemic sarcophytol A and their stereoisomers can be produced by the (2,3) Wittig rearrangement reaction in which an organic metal such as rt-butyllithium or lithium diisopropylamide is reacted.

[C25]

[0030]

[Examples] The present invention will be explained in more detail with reference to Examples below, but the present invention is not limited by the Examples unless it exceeds the gist thereof.

Synthesis example 1

Under an argon atmosphere, 56 ml of a 0.5M toluene solution of potassium bis(trimethylsilyl)amide was added to a toluene solution (55 ml) of 2-(diethylphosphono)-isovaleronitrile (6.54 g, 30 mmol) at -70 The mixture was added to the bath while stirring. After 30 minutes, add geranial (3.80 g, 25 mmol) at the same temperature while continuing to stir.
) was added, and the temperature was raised to room temperature over about 10 hours. Water was added to the reaction mixture, the layers were separated, and the organic layer was washed with saturated aqueous sodium bicarbonate solution and saturated brine, and dried (anhydrous MgSO4
), filtration, and concentration, and the residue obtained was subjected to silica gel column chromatography (developing solution: n-hexane: ethyl acetate 100%
:1) to obtain the desired 2-(1-methylethyl)-
5,9-dimethyl 2,4,8-decatrienitrile (
4.87 g, 90%, 2Z:2E=22.4:1) was obtained. The spectral data of the 2Z form is shown below.

IR (film) cm-1; 2980,2
940, 2890, 2220, 1640, 1450, 1
390,1375,1295,1225,1105,1
030. NMR (CDCl3, 250MHz) δppm
;1.17(d,J=6.8Hz,6H,CH(CH3
)2), 1.61, 1.69 (each bs, each 3
H, -C=CCH3), 1.83 (d, J=1.2Hz
, 3H, -C=CCH3), 2.1-2.2(m, 4H
, -CH2CH2-), 2.53 (hep, J=6.8
Hz, 1H, CH(CH3)2), 5.08(m, 1H
, -C=CHCH2-), 6.28, 6.82 (each
d, J=11.5Hz, each 1H,=CH-CH=
).

Synthesis example 2

embedded image 2-(1-methylethyl)-5,9-dimethyl 2,4,
8-decatrienenitrile (2Z form, 217mg, 1m
mol) of 1M diisobutylaluminum hydride in 4 ml of n-hexane solution at -70°C under an argon atmosphere.
2 ml of toluene solution was added dropwise while stirring. After 1 hour at the same temperature, 0.8 ml of water was added, the bath was removed and the mixture was stirred well. The white solid formed was filtered off and washed (n-hexane), and the filtrate was vigorously stirred with 5 ml of a 10% oxalic acid aqueous solution for 3 hours. . Separate the organic layer, wash with water, and dry (anhydrous MgSO
4), filtered and concentrated. All of the above operations were performed under an argon atmosphere. The obtained residue was subjected to silica gel chromatography (developing solution: n-hexane: ethyl acetate 50:1).
) to obtain the desired 2-(1-methylethyl)-5,
9-dimethyl 2,4,8-decatrienal (198m
g, 90%) was obtained.

IR (film) cm-1; 2980,2
940, 2880, 1670, 1630, 1455, 1
375, 1295, 1235, 1135, 1105, 1
075. NMR (CDCl3, 250MHz) δppm
;1.07(d,J=6.8Hz,6H,-CH(CH
3) 2), 1.62, 1.69 (each bs, each
3H, -C=CCH3), 1.89 (d, J=1.0H
z, 3H, -C=CCH3), 2.1-2.3 (m, 4
H, -CH2CH2-), 2.91 (hep, J=6.
8Hz, 1H, -CH(CH3)2), 5.10(m,
1H, =CH-CH2-), 6.83, 7.14 (each d, J = 12.0Hz, each 1H, =CH-C
H=), 10.29(s, 1H, -CHO).

003
5] Synthesis example 3

embedded image 2-(1-methylethyl)-5,9-dimethyl 2,4,
8-decatrienenitrile (2.0g, 9.2mmol
) m-chloroperbenzoic acid (purity 80%, 2.0 g, 9
．． 3 mmol) was gradually added. After stirring in an ice water bath for 1 hour, the bath was removed and stirring was continued for an additional 3 hours. After adding a saturated aqueous sodium bicarbonate solution and stirring vigorously for 30 minutes, the organic layer was separated, washed with water, dried, and concentrated. The resulting residue was subjected to silica gel column chromatography (developing solution: n-hexane: ethyl acetate 10:1). The desired epoxy body (2.08 g, 97%) was obtained.

IR (film) cm-1; 2970,2
940, 2880, 2210, 1640, 1460, 1
380,1120,1025. NMR (CDCl3, 250MHz) δppm; 1.1
7 (d, J=6.8Hz, 6H, CH(CH3)2),
1.27, 1.32 (each s, each 3H, OC (
CH3)2), 1.6-1.8(m,2H,=CCH2
CH2-), 1.86 (s, 3H, = CCH3), 2.
2-2.3 (m, 2H, =CCH2CH2-), 2.5
4(hep, J=6.8Hz, 1H, CH(CH3)2
), 2.72 (t, J=6.2Hz, 1H, -CHO-
), 6.31 (dd, J=0.9, 11.5Hz, 1H
, =CH-CH=), 6.83 (d, J=11.5Hz
, 1H, =CH-CH=).

Synthesis example 4

[Chemical formula 29] Epoxy body obtained in Synthesis Example 3 (1.83 g, 7.85 mm
Aluminum triisopropoxide (1.60 g, 7.84 mmol) was added to a dry toluene solution (16 ml) of
1) was added and heated on an oil bath at 110°C under N2 atmosphere for 8 hours. After cooling, the mixture was diluted with n-hexane and thoroughly mixed with 2N hydrochloric acid. The organic layer was washed with water and a saturated aqueous sodium bicarbonate solution, dried, and concentrated. The resulting residue was subjected to SiO2 column chromatography (developing solution: n-hexane: EtO
Ac = 6:1) to obtain the target product, an allyl alcohol compound (1.80 g, 98%).

IR (film) cm-1; 3450,2
980, 2950, 2880, 2210, 1640, 1
450, 1390, 1295, 1030, 900. NMR (CDCl3, 250MHz) δppm; 1.1
4 (d, J=6.9Hz, 6H, -CH(CH3)2)
, 1.6-1.75 (m, 2H, =CCH2CH2-)
, 1.71 (s, 3H, = CCH3), 1.82 (d,
J=1.0Hz, 3H, =CCH3), 2.0-2.3
(m, 2H, =CCH2CH2-), 2.50(hep
, J=6.9Hz, 1H, -CH(CH3)2), 4.
03 (t, J=6.3Hz, -CHOH), 4.84,
4.94 (each bs, each 1H, C=CH2),
6.27(dd, J=1.0, 11.5Hz,=CHa
-CHb=), 6.8 (d, J=11.5Hz, =CH
a-CHb=).

Synthesis Example 5

embedded image Allyl alcohol compound obtained in Synthesis Example 4 (470 mg, 2.
02 mmol) and 3,3-dimethoxy-2-methyl-2
-2,4-dinitrophenol (28 mg, 0.15 mmol) was added to a mixture of butanol (1.48 g, 10 mmol).
mol) and heated on an oil bath at 140° C. for 5 hours under an argon atmosphere. After cooling, remove excess reagent under reduced pressure,
The residue was subjected to SiO2 column chromatography (developing solution n
-Hexane:ethyl acetate 6:1) to obtain the desired α-hydroxyketone (609 mg, 95%).

IR (film) cm-1; 3520,2
990, 2950, 2890, 2220, 1715, 1
640, 1470, 1450, 1370, 1165, 1
075,1025,965. NMR (CDCl3, 250MHz) δppm; 1.1
4 (d, J=6.8Hz, 6H, -CH(CH3)2)
, 1.35 (s, 6H, -C(CH3)2OH), 1.
61 (s, 3H, = CCH3), 1.80 (d, J = 1
．． 2Hz,=CCH3), 2.1(m,4H,=CCH
2CH2C=), 2.26(bt, J=7.5Hz, 2
H, -CH2CH2C=O), 2.50 (hep, J=
6.8Hz, 1H, -CH(CH3)2), 2.63(
t, J=7.5Hz, 2H, -CH2C=O), 5.0
9 (bm, 1H, =CHCH2-), 6.24 (dd,
J=0.8, 11.5Hz, 1H, =CHa-CHb=
), 6.79 (dd, J=0.7, 11.5Hz, 1H
,=CHa−CHb=).

Synthesis Example 6

embedded image 2-(diethylphosphono)-isovaleronitrile (8.
72 g, 40 mmol) in toluene (75 ml) was gradually added with 75 ml of a 0.5 M toluene solution of potassium bis(trimethylsilyl)amide while stirring at -70°C under an argon atmosphere, the bath was removed, and the mixture was heated at room temperature for 30 minutes. Stirred. The mixture was cooled to −70° C. again, farnesal (5.88 g, 26.7 mmol) was added while stirring, and the temperature was raised to room temperature. Water was added to the reaction mixture, and the organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, and then dried over anhydrous magnesium sulfate. The residue obtained by filtration and concentration was purified by silica gel column chromatography (developing solution: n-hexane:ethyl acetate = 100:1) to obtain the desired 2-(1-methylethyl)-5,
9,13-trimethyl 2,4,8,12-tetradecatetraenenitrile (7.23g, 96%, 2Z:2E=
25.6:1) was obtained. The spectral data of the 2Z form is shown below.

IR (film) cm-1; 2980,2
940, 2210, 1640, 1450, 1390, 1
290, 1225, 1110, 1030. NMR (CDCl3, 250MHz) δppm; 1.1
4(d, J=6.8Hz, 6H, CH(CH3)2),
1.58 (bs, 3H×2, -C=CCH3), 1.6
5 (bs, 3H, -C=CCH3), 1.81 (d, J
=1.2Hz, 3H, -C=CCH3), 1.9-2.
2(m, 8H, -CH2CH2 -x2), 2.50(
hep, J=6.8Hz, 1H, -CH(CH3)2)
,5.06(m,1H,=CHCH2-),6.26,
6.80 (each d, J=11.5Hz, each 1H,=
CH-CH=).

Synthesis Example 7

embedded image 2-(1-methylethyl)-5,9,1 obtained in Synthesis Example 6
A solution of 3-trimethyl 2,4,8,12-tetradecatetraenenitrile (856 mg, 3.0 mmol) in n-hexane (30 ml) was added at -70°C under an argon atmosphere.
0.0% of diisobutylaluminum hydride while stirring at
6 ml of 5M toluene solution was added, and after 1 hour, 3 ml of water was added, the bath was removed, and the mixture was thoroughly stirred. After the obtained white solid was filtered off, the filtrate obtained by washing was concentrated. Dissolve this residue in n-hexane (10 ml) and add 10% aqueous oxalic acid solution (5 ml).
ml) and stirred for 3 hours, the organic layer was extracted and separated, washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated, and then subjected to silica gel column chromatography (developing solution n
-hexane:ethyl acetate=10:1) to obtain the desired formyl compound (2-(1-methylethyl)-5,9,1
3-Trimethyl 2,4,8,12-tetradecatetraenal) (865 mg, 84%) was obtained.

IR (film) cm-1; 2980,2
940, 2210, 1640, 1450, 1390, 1
290, 1225, 1110, 1030. NMR (CDCl3, 250MHz) δppm; 1.0
7 (d, J=6.8Hz, 6H, -CH(CH3)2)
, 1.59, 1.61, 1.67 (respectively bs, 3H×
3, -C=CCH3), 1.89 (d, J=1.0Hz
, 3H, -C=CCH3), 2.0-2.2(m, 8H
, -CH2 CH2-×2), 2.91(hep, J=
6.8Hz, 1H, -CH(CH3)2), 5.10(
m, 1H, -C=CCH3), 6.81, 7.16 (each d, J=12.0Hz, each 1H, =CH-CH
=), 10.29(s, 1H, -CHO).

0045
]Synthesis example 8

embedded image To a solution of the conjugated nitrile compound (208 mg, 0.73 mmol) in methylene chloride (3 ml) was added m-chloroperbenzoic acid (purity 80%; 165 mg, 0.5 mg, while stirring on an ice-water bath).
(equivalent to 77 mmol) was added. After 2 hours, saturated aqueous sodium hydrogen carbonate solution (2 ml) was added and stirred well. The organic layer was separated, washed with water, dried (MgSO4), and concentrated. The residue obtained was subjected to SiO2 column chromatography (developing solution n
-hexane:ethyl acetate=7:1) to obtain the desired epoxy compound (165 mg, 75%).

IR (film) cm-1; 2980,2
940, 2890, 2220, 1640, 1455, 1
380, 1220, 1120, 1025, 900, 87
5. NMR (CDCl3, 250MHz) δppm; 1
．． 13(d, J=6.8Hz, 6H, -CH(CH3)
2), 1.23, 1.27 (each s, each 3H, O
C(CH3)2),1.5-1.7(m,2H,-OC
HCH2), 1.60 (d, J=0.6Hz, =CCH
3), 1.80 (d, J=1Hz, =CCH3), 2.
0-2.2(m,2H,-OCHCH2CH2-),2
．． 14 (m, 4H, =CCH2CH2C=), 2.50
(hep, 1H, J=6.8Hz, -CH(CH3)2
), 2.67 (t, J=6.3Hz, 1H, -CHO-
), 5.1 (bm, 1H, =CH-(CH2)2-),
6.24(bd, J=11.5Hz, 1H,=CHa-
CHb=), 6.79 (d, J=11.5Hz, 1H,
=CHa-CHb=).

Synthesis Example 9

embedded image A solution of tetraenenitrile (65 mg, 0.23 mmol) in aqueous tetrahydrofuran (THF 1 ml, H2O
N-bromosuccinimide (49 mg, 0.28 mmol) was added to the solution (49 mg, 0.28 mmol) under ice-cooling and stirring. After 30 minutes, it was confirmed that the raw materials had disappeared, and most of the tetrahydrofuran was distilled off under reduced pressure. The residue was extracted with ethyl ether, the organic layer was washed with water, dried (MgSO4), and the crude product obtained was subjected to silica gel chromatography (developing solution n-
Hexane:ethyl acetate=6:1) to obtain the desired monoepoxy compound (58 mg, 67%).

IR (film) cm-1; 3500,2
980, 2950, 2890, 2210, 1635, 1
465, 1450, 1385, 1365, 1335, 1
200,1165,1120,1025,965,90
5. NMR (CDCl3, 250MHz) δppm; 1.1
3 (d, J=6.8Hz, 6H, -CH(CH3)2)
, 1.30, 1.31 (s, 3H, -OC(CH
3)2),1.58(s,3H,=CCH3),1.7
-2.4 (m, 4H, -CHBrCH2CH2), 1.
80 (d, J=1.2Hz, 3H,=CCH3), 2.
15(m,4H,=CCH2CH2C=), 2.49(
hep, J=6.8Hz, 1H, -CH(CH3)2)
, 3.92 (dd, J=1.8, 11.2Hz, 1H,
-CHBr-), 5.15 (bm, 1H, =CHCH2
CH2-), 6.24 (dd, J=11.5, 1.0H
z, 1H, -CHa-CHb=), 6.79 (d, J=
11.5Hz, 1H, =CHa-CHb=).

Synthesis Example 10

embedded image Bromohydrin compound obtained in Example 3 (380 mg, 1.0
Anhydrous potassium carbonate (550 mg, 4.0 mmol) was added to a solution of Mmol) in methanol (5.0 ml), and the mixture was vigorously stirred for 2 hours. After distilling off methanol under reduced pressure, ice water was added and extracted with ethyl ether. The organic layer was washed with water and dried (
MgSO4), and the crude product obtained by concentration was subjected to silica gel chromatography (developing solution: n-hexane: ethyl acetate = 7
:1) to obtain the same epoxy compound as that obtained in Synthesis Example 8 (285 mg, 95%).

Synthesis Example 11

[Chemical formula 36] The epoxy compound obtained in Synthesis Example 10 (451 mg, 1.5
mmol) in aqueous THF (THF:H2O=3:1,5
0 ml), a catalytic amount of perchloric acid was added thereto, and the mixture was left at room temperature for 6 hours. After adding a small amount of saturated aqueous sodium hydrogen carbonate solution, most of the THF was distilled off under reduced pressure, and the residue was extracted with diethyl ether. Drying of the organic layer (MgSO
4) The residue obtained by concentration was subjected to SiO2 column chromatography (developing solution n-hexane: ethyl acetate 3:1 to 2:1).
) to obtain the desired α-diol (435 mg
, 91%).

IR (film) cm-1; 3450,2
970, 2930, 2870, 2210, 1635, 1
450, 1385, 1290, 1220, 1160, 1
075,1015,915. NMR (CDCl3,25
0MHz) δppm; 1.12, 1.16 (s, respectively
3H, -C(CH3)2OH), 1.13(d
, J=6.8Hz, 6H, -CH(CH3)2), 1.
3-1.7 (m, 2H, =CCH2CH2CHOH-)
, 1.59 (d, J=0.6Hz, 3H,=CCH3)
, 1.80 (d, J=1.1Hz, 3H,=CCH3)
,2.0-2.3(m,6H,=CCH2CH2CHO
H,=CCH2CH2C=), 2.49(hep, J=
6.8Hz, 1H, -CH(CH3)2), 3.30(
bd, J=10.3Hz, 1H, -CHOH), 5.1
3 (bm, 1H, =CHCH2-), 6.23 (dd,
J=0.7, 11.5Hz, 1H, =CH-CH=),
6.79 (dd, J=0.6, 11.5Hz, 1H,=
CH-CH=).

Synthesis Example 12

[Chemical formula 37] Dimethyl sulfoxide (1
．． 56 g, 20 mmol) was dissolved on a -78°C bath,
Cooled. To this was added trifluoroacetic anhydride (3.2 g, 15 mmol)
) in methylene chloride (5 ml) was added dropwise with stirring. After 30 minutes, methylene chloride (10
ml) solution was added over a period of 10 minutes, and 30 minutes after the completion of the dropwise addition, triethylamine (4 ml) was subsequently added dropwise over a period of 10 minutes. The bath was removed, the temperature was raised to room temperature, ice water was added, the layers were separated, and the organic layer was washed with water, dried (MgSO4), and the residue obtained by concentration was subjected to SiO2 column chromatography (developing solution: n-hexane: ethyl acetate: 6: 1) and the same α-hydroxyketone body (2.4 g, 88%) as obtained in Synthesis Example 5.
I got it.

Synthesis Example 13

[Chemical formula 38] Add 3g of fresh yeast to a 100ml eggplant flask,
Add 0 ml of water to dissolve. 3. While stirring at room temperature.
5g of D-glucose was added. When bubbles start to appear (~3
After continuing stirring for about 30 minutes, the ketone body (100 mg, 0.3158 mmol) was added to 3 ml of ethanol.
1) was added and stirred at room temperature for 2 days. Ethyl acetate (approximately 30 ml) and Celite were added to the reaction mixture, and after stirring for 1 hour, the yeast Celite was removed by filtration. The organic layer and aqueous layer of the filtrate were separated, and the aqueous layer was extracted with ethyl acetate (twice). The first ethyl acetate layer and the extracted organic layer were combined with water (once) and saturated brine (
The mixture was washed with water (once) and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 130.2 mg of crude product. This was separated by SiO2 column chromatography (developing solution: hexane: ethyl acetate = 2:1), and the raw material was recovered at 30
．． 3 mg and 69.5 mg (in terms of recovery, 98%) of the desired diol compound were obtained.

[α]26D+20.0 (c=0.99, MeOH). IR (film) and NMR (CDCl3) spectral data are the same as the DL-form obtained in Synthesis Example 11. MS (EI); m/z 319 (M+), 301, 2
60 (BP). HRMS (EI); Calculated value 319,25
14 Actual value C20H33O2N 319,19
31

Synthesis Example 14

[Chemical formula 39] Optically active diol obtained in Synthesis Example 13 (319 mg, 1
．． 0 mmol) and triethylamine (121 mg, 1.
Methanesulfonyl chloride (125 mg, 1.1 mmol) was added to a solution of 2 mmol) in methylene chloride (4 ml), and the mixture was stirred at room temperature overnight. Ice water was added to the reaction mixture, and the organic layer was washed sequentially with water, 1N aqueous hydrochloric acid, water, and saturated aqueous sodium bicarbonate solution, and then dried (MgSO4).
The residue obtained by concentration was subjected to silica gel chromatography (developing solution: n-hexane:ethyl acetate = 5:1) to obtain the desired monomesylate (361 mg, 91%).

[α]24D +10.7° (c=1.6, MeOH
) IR (film) cm-1; 3530, 2980, 2
950, 2880, 2210, 1635, 1470, 1
450, 1390, 1355, 1340, 1175, 1
140, 1030, 975, 940, 925, 915. NMR (CDCl3, 250MHz) δppm; 1.1
3 (d, J=6.8Hz, 6H, -CH(CH3)2)
, 1.21, 1.23 (each s, each 3H, -OC
(CH3)2), 1.59(s,3H,=CCH3),
1.6-1.75 (m, 2H, -OCHCH2-), 1
．． 80 (d, J=1Hz, 3H,=CCH3), 2.0
-2.3 (m, 2H, -OCHCH2CH2-), 2.
15(m,4H,=CCH2CH2C=), 2.50(
hep, J=6.8Hz, 1H, -CH(CH3)2)
,3.10(s,3H,-OSO2CH3),4.53
(dd, J=8.5, 4.0Hz, 1H, -CHOSO
2-), 5.14 (bm, 1H, =CHCH2CH2-
), 6.24 (bd, J=11.5Hz, = CHa-C
Hb=), 6.80 (d, J=11.5Hz,=CHa
-CHb=).

Synthesis Example 15

embedded image Monomesylate obtained in Synthesis Example 14 (286 mg, 0.7
Anhydrous potassium carbonate (298 mg, 2.1 mmol) was added to a solution of 2 mmol) in methanol (3 ml) on an ice water bath, and the mixture was stirred for 2 hours. Ice water was added to the residue obtained by distilling off methanol under reduced pressure, and the mixture was extracted with ether. The crude product obtained by washing the organic layer with water, drying (MgSO4), and concentration was subjected to silica gel chromatography (developing solution: n-hexane: ethyl acetate = 7:1) to obtain the desired epoxy compound (200 mg, 92%). I got it. [α]24.5D -3.8° (c=1.0, MeO
H) Spectral data are the same as those of the DL-epoxy compound obtained in Synthesis Examples 8 and 10.

Synthesis Example 16

embedded image Epoxy body obtained in Synthesis Example 15 (391 mg, 1.3 mm
Aluminum triisopropoxide (265 mg, 1.3 mmol) was added to a toluene (3 ml) solution of ol) and heated to 110° C. for 6 hours under N2 atmosphere. After cooling, it was diluted with n-hexane and thoroughly stirred with 2N hydrochloric acid. The organic layer was separated, washed sequentially with water and a saturated aqueous sodium bicarbonate solution, dried (MgSO4), and concentrated.
The desired allyl alcohol compound (372 mg, 95%) was obtained by subjecting it to iO2 column chromatography (developing solution: n-hexane: ethyl acetate = 6:1).

[α]25D −6.9° (c=0.62, MeOH
) IR (film) cm-1; 3380, 2990, 2
950, 2895, 2220, 1635, 1450, 1
390,1295,1060,1025,900. NMR (CDCl3, 250MHz) δppm; 1.1
4 (d, J=6.8Hz, 6H, -CH(CH3)2)
, 1.60 (s, 3H, = CCH3), 1.6-1.7
(m, 2H, -CH(OH)CH2-), 1.70(s
,3H,=CCH3),1.81(d,J=1Hz,3
H, = CCH3), 1.9-2.1 (bm, 2H, -C
H(OH)CH2CH2-),2.15(m,4H,=
CCH2CH2C=), 2.50(hep, 1H, J=
6.8Hz, -CH(CH3)2), 4.01(bm,
-CH(OH)-), 4.81(m, 1H, -C=CH
aHb), 4.91 (bs, 1H, -C=CHaHb)
,5.11(bm,1H,=CH-(CH2)2-),
6.25 (bd, J=11.5Hz, 1H,=CHa-
CHb=), 6.80 (d, J=11.5Hz, 1H,
=CHa-CHb).

Synthesis Example 17

embedded image Nitrile alcohol obtained in Synthesis Example 16 (486 mg, 1
．． 6 mmol) was dissolved in n-hexane (10 ml),
Under an argon atmosphere, a solution of 0.9 M diisobutylaluminum hydride in n-hexane (5.3 ml) was added dropwise through a syringe while stirring on a bath at a low temperature (-78°C). After the dropwise addition was completed, the refrigerant bath was removed and the mixture was stirred at room temperature for 3 hours. Cool again in a refrigerant bath, and add 10% acetic acid aqueous solution (9 ml).
After adding the solution, the bath was changed to an ice water bath and stirring was continued for an additional 6 hours. The organic layer was separated, washed with water (twice), washed with a saturated aqueous sodium bicarbonate solution, dried (MgSO4), and concentrated. The resulting residue was subjected to SiO2 column chromatography (developing solution: n-hexane: ethyl acetate 6:1). The desired formyl compound (338 mg, 69%) was obtained.

IR (film) cm-1; 3450,2
970, 2940, 2880, 1665, 1625, 1
450, 1390, 1295, 1230, 1180, 1
130,1100,1065,1020,995,89
5. NMR (CDCl3, 250MHz) δppm; 1.0
2 (d, J=7.0Hz, 6H, -CH(CH3)2)
, 1.5-1.65(m, 2H, -C(OH)CH2-
), 1.59 (d, J=0.8Hz, 3H,=CCH3
), 1.67 (s, 3H, = CCH3), 1.85 (d
, J=1.3Hz,3H,=CCH3), 1.99(b
q, J=7.5Hz, 2H, -C(OH)CH2CH2
-), 2.17 (m, 4H, =CCH2CH2C=),
2.86(hep, J=7.0Hz, 1H, -CH(C
H3)2), 3.98 (bt, J=5.7Hz, 1H,
-CH(OH)-), 4.78, 4.88 (m, respectively)
1H, -C=CH2), 5.11 (bm, 1H, respectively)
=CHCH2CH2-), 6.79 (bd, J=12.
0Hz; 1H, =CHa-CHb=), 1.09(d,
J=12.0Hz, 1H, =CHa-CHb=), 10
．． 23(s, 1H, -CHO).

Synthesis Example 18

embedded image Diol compound obtained in Synthesis Example 13 (104 mg, 0.33 m
85 mol) of acetic anhydride in pyridine (0.5 ml) solution.
mg of lupyridine was added and left at room temperature for 2 days. Excess reagents were distilled off under reduced pressure, and the residue was subjected to SiO2 column chromatography (developing solution: n-hexane: ethyl acetate 3:
1) and the desired monoacetate (95 mg, 8
1%). [α]26D +9.2° (c=0.75, MeOH
). IR (film) cm-1: 3500, 2960, 29
30, 2870, 2200, 1730, 1630, 14
65, 1450, 1370, 1240, 1160, 11
40,1050,1040,950,875. NMR (CDCl3, 250MHz) δppm; 1.1
3 (d, J=6.8Hz, 6H, -CH(CH3)2)
, 1.15, 1.16 (each s, each 3H, -OC(C
H3)2), 1.57(s,3H,=CCH3),1.
6-1.8 (m, 2H, -OCHCH2-), 1.80
(d, J=0.6Hz, 3H,=CCH3), 1.85
(s, 1H, -OH), 1.9-2.0 (m, 2H, -
OCHCH2CH2-), 2.07(s,3H,-OC
OCH3),2.14(m,4H,=CCH2CH2C
=), 2.49 (hep, J=6.8Hz, 1H, -C
H(CH3)2), 4.75 (dd, J=3.3, 9.
5Hz, 1H, -CHOCOCH3), 5.06 (bm
, 1H, = CH-), 6.24 (bd, J = 11.5H
z, 1H, = CHa-HbC =), 6.79 (d, J =
11.5Hz, 1H, =CHa-HbC=).

Synthesis Example 19

embedded image Monoacetate obtained in Synthesis Example 18 (184 mg, 0.5 mg)
To a solution of 51 mmol) in pyridine (1.5 ml) was added phosphorus oxychloride (0.06 ml) while stirring on an ice-water bath. After removing the cooling bath, the mixture was stirred for an additional 3 hours. The reaction mixture was dissolved in ice water and diethyl ether, and the layers were separated. The organic layer was washed successively with water, 1N aqueous hydrochloric acid, water, and saturated aqueous sodium bicarbonate solution, and the residue obtained by drying (MgSO4) and concentration was subjected to SiO2 column chromatography (developing solution: n-hexane: ethyl acetate 10:1). The desired allyl acetate compound (156 mg, 89%) was obtained.

[α]25D +10.7° (c=1.0, MeOH
). IR (film) cm-1; 2970, 2930, 28
80, 2210, 1740, 1635, 1430, 13
70,1240,1050,1025,910. 1H-NMR (250MHz, CDCl3) δppm;
1.14(d,6H,J=6.8Hz,-CH(CH3
)2), 1.58, 1.69(s, each 3H, = CCH
3), 1.6-1.8(m, 2H, -C(OAc)CH
2-), 1.80 (d, 3H, J=1.0Hz, = CC
H3), 1.8-2.0(m, 2H, -C(OAc)C
H2CH2-),2.02(s,3H,-OAc),2
．． 1(m,4H,=CCH2CH2C=), 2.50(
hep, 1H, -CH(CH3)2), 4.86(m,
1H,=CHaHb), 4.90(bs,1H,=CH
aHb), 5.0-5.2 (m, 2H, =CHCH2-
and -CH(OAc)-), 6.24(bd,1H,J=
11.5Hz, =CHa-CHb=), 6.79(d,
1H, J=11.5Hz, =CHa-CHb=).

Synthesis Example 20

embedded image Acetate obtained in Synthesis Example 90 (240 mg, 0.7 m
A 28% methanol solution (0.02 ml) of sodium methoxide was added to a methanol (5 ml) solution of sodium methoxide at ice-cold temperature.
After adding 1), the bath was removed and the mixture was left at room temperature for 20 hours. After neutralization by adding acetic acid, methanol was distilled off, water and diethyl ether were added to the residue, the layers were separated, the organic layer was washed with water, the saturated sodium bicarbonate aqueous solution was washed, the residue obtained by drying (MgSO4), and concentration was applied to a SiO2 column. It was purified by chromatography (developing solution: n-hexane: ethyl acetate 6:1) to obtain the desired alcohol (190 mg, 90%). [α]26D +7.3° (c=0.45, MeOH
). The spectral data are the same as the compound of Synthesis Example 16.

Synthesis Example 21

embedded image Formyl compound obtained in Synthesis Example 17 (648 mg, 2.14 m
Sodium borohydride (30 mg, 0.8 ml) was added to a methanol (6 ml) solution with stirring under ice cooling.
mol) was added. After 30 minutes, methanol was distilled off under reduced pressure, the residue was dissolved in diethyl ether and water, the layers were separated, and the organic layer was washed with water, dried, and concentrated. The residue was subjected to SiO2 column chromatography (developing solution: n-hexane: ethyl acetate 5
: Purified by 1) to obtain diol form (632 mg, 96%)
I got it.

[α]22D = +14° (c = 0.64, CHCl
3). IR (film) cm-1; 3350, 2960
,2930,2880,1650,1445,1380
,1305,1235,1100,1065,1010
,965,895. NMR (CDCl3, 250MHz
) δppm; 1.05 (d, J=6.9Hz, 6H, -
CH(CCH3)2), 1.5-1.7(m,2H,=
CCH2CH2CH(OH)-), 1.59, 1.68
, 1.74 (each s, each 3H, =CCH3×3), 2
．． 01(bt, J=7.6Hz, 2H,=CCH2CH
2CH(OH)-), 2.1-2.2(m, 4H, =C
CH2CH2C=), 2.45 (hep, J=6.9H
z, 1H, -CH(CH3)2), 3.98(bt, J
=6.3Hz, 1H, -CH(OH)-), 4.19,
4.22 (each bd, J=12.3Hz, each 1H, -
CHaHbOH), 4.79, 4.88 (each bs, each 1H, -C=CH2), 5.13 (bm, 1H, =C
HCH2CH2-), 6.12(m,2H,=CH-C
H=).

Synthesis Example 22

[Chemical formula 47] Epoxy body (Te
trahedron detters, 31,402
5 (1990)) (594 mg, 2.5 mmol)
40 ml of anhydrous toluene was added to dissolve the mixture under an argon atmosphere, and then 2.5 equivalents of aluminum triisopropoxide (1.3 g, 6.2 mmol) was added and heated under reflux with stirring. After 8 hours, TLC (CH2Cl
2:EtoAc=5:1) to confirm the disappearance of the raw material. The reaction mixture is cooled to room temperature, diluted with 50 ml of ethyl acetate, 2 ml of water and Celite are added and stirred for 20 minutes, then anhydrous magnesium sulfate is added and stirred for an additional 30 minutes. Inorganic substances were removed by filtration, and the solvent was distilled off under reduced pressure to obtain 841 mg of a crude product. This was purified using SiO2 column chromatography (developing solution: hexane: ethyl acetate = 4:1), and the allyl alcohol form (5
49 mg, 92.2%) was obtained.

[α]18D -4.4° (c=0.7
, MeOH). IR (film) cm-1; 3420, 2940, 28
55, 1680, 1660, 1445, 1390, 11
00,900. NMR (CDCl3, 90MHz) cm
-1; 1.64, 1.66, 1.72 (s each, 3 each
H,=CCH3),1.9-2.3(m,8H,-CH
2CH2-×2), 4.01 (dd, J=5.7, 5.
7Hz, 1H, -CHOH-), 4.14 (d, J=6
．． 8Hz, 2H, -CH2OH), 4.84, 4.93
(each d, J=0.9Hz, each 1H,=CHaHb)
, 5.17 (bm, 1H, =CH-), 5.41 (bt
, J=6.8Hz, 1H, =CHCH2OH).

Synthesis Example 23

[Chemical Formula 48] Allyl alcohol (549 mg, 2.3050 mmol) was placed in a heat-dried 100 ml two-necked flask, dissolved in 25 ml of anhydrous pyridine under an argon atmosphere, and 1 equivalent of benzoyl chloride (324 mg) was added with stirring at room temperature.
, 2.3 mmol) was added dropwise over 10 minutes. T.L.C.
(hexane: ethyl acetate = 5:1) to monitor the reaction,
After 0 minutes, when some raw material remained, ice water was added to stop the reaction. After extraction with ethyl acetate, the organic layer was washed with saturated copper nitrate solution (once), water (twice), and saturated brine (once), and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 841 mg of a crude product. This is SiO
They were separated by two-column chromatography (developing solution: hexane:ethyl acetate = 10:1), and the monobenzoate form 024 591.4, g (94.78% in terms of recovery) and the dibenzoate form (35.0 mg, 4.30%) ) and 114.0 mg of recovered raw material were obtained.

[α]25D -3.8° (c=1.0
, MeOH). IR (film) cm-1; 3430, 2950, 28
55,1730,1600,1435,1380,10
75,1015,900,720. NMR (CDCl3, 90MHz) δppm; 1.62
, 1.64, 1.72 (each s, each 3H, =CCH3
), 1.9-2.3 (m, 8H, -CH2CH2-x2
), 4.03 (dd, J=6.2, 6.2Hz, 1H,
-CHOH-), 4.82, 4.94 (respectively d, J=1
Hz, each 1H, = CHaHb), 4.85 (d, J =
6.6Hz, 2H, -CH2O-), 5.16(bm,
1H,=CH-), 5.48(bt, J=6.6Hz,
1H,=CHCH2O-),7.3-7.7,8.0-
8.1 (each m, total 5H, ph).

Synthesis Example 24

embedded image The monobenzoate (660 mg, 1.9 mmol) was placed in a dry 20 ml two-necked flask, and under an argon atmosphere, 2.5 ml of anhydrous dimethylformamide and 4 equivalents of imidasol (52.5 mg, 7.7 mmol) were added. ) and stirred at room temperature for 10 minutes, then 3 equivalents of t-butyldiphenylchlorosilane (1.6 g, 5.8 mmol) were added and stirred at room temperature. After 1 hour, TLC (hexane:
Disappearance of the raw material was confirmed using ethyl acetate (4:1). Water was added to the reaction mixture, extracted with ether, and the organic layer was diluted with water (2
The mixture was washed with saturated brine (once) and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by SiO2 column chromatography (developing solution: hexane:acetic ether = 10:1) to obtain a silyl ether (1.05 g, 93.7%).

[α]22D +20.3° (c=1.0, CHCl
3) IR (film) cm-1; 3075, 2940,
1730, 1600, 1590, 1475, 1423,
1265, 1110, 1060, 1000, 900, 8
20,740,710. NMR (CDCl3, 90MH
z) δppm; 1.06 (s, 9H, -C(CH3),
1.42, 1.67, 1.75 (each s, each 3H, =
CCH3), 1.6-1.9(m,2H,=CCH2C
H2CHO-), 2.0-2.1(m,6H,=CH2
CH2CHO- and =CCH2CH2C=), 4.06(
t, J=5.8Hz, 1H, -CHO-), 4.72(
bs, 2H, = CH2), 4.82 (d, J = 7.3H
z, =CHCH2O-), 4.94 (bm, 1H, =C
H-), 5.43 (bt, J=7.3Hz, 1H, =C
HCH2O-), 7.3-7.8, 7.9-8.1 (m each, total 15H, -SiPh2, -COPh).

Synthesis Example 25

embedded image Monobenzoate (210mg, 0.36mmol)
and 4 ml of methanol-tetrahydrofuran (1:1)
Lithium hydroxide, monohydrate (80 mg, 1.
9 mmol) and stirred at room temperature. 1 hour later, TL
Disappearance of the raw material was confirmed with C (hexane: ethyl acetate = 4:1). The solvent was distilled off, water was added to the residue, extracted with ethyl acetate, washed with water (twice) and saturated brine (once), and dried over anhydrous magnesium sulfate. 182.4m of crude product obtained by distilling off the solvent under reduced pressure
I got g. This was subjected to SiO2 column chromatography (
Purification was performed using a developing solution (hexane:ethyl acetate=10:1) to obtain an alcohol (136.9 g, 79%).

[α]24D +22.4° (c=0.99, MeO
H). IR (film) cm-1; 3400, 2940
,2850,1470,1460,1440,1425
,1385,1110,1060,1000,900,
820,740,700. NMR (CDCl3, 90M
Hz) δppm; 1.06 (s, 9H, -C(CH3)
3), 1.42, 1.66, 1.69 (s each, 3 each
H,=CCH3), 1.6-1.7(m,2H,=CC
H2CH2CHO-), 1.9-2.1 (m, 6H, =
CCH2CH2CHO- and =CCH2CH2C=),4
．． 08 (t, J=7.0Hz, 1H, -CHO-), 4
．． 13 (d, J=7.3Hz, 2H, =CCH2O-)
, 4.72 (bs, 2H, = CH2), 4.92 (bm
,1H,=CH-),5.38(bt,J=7.3Hz
, 1H, =CHCH2O-), 7.3-7.5, 7.6
-7.8 (each m, total 10H, -Ph x 2).

[
Synthesis Example 26

[Chemical formula 51] In a heat-dried 50 ml three-necked flask under an argon stream,
0 ml of anhydrous dichloromethane and 2 equivalents of oxalyl chloride (326 mg, 2.6 mmol) were taken, cooled to -78°, and stirred. A solution of 3 equivalents of dimethyl sulfoxide (300 mg, 3.84 mmol) in anhydrous dichloromethane (1 ml) was slowly added dropwise thereto. The liquid gradually turned white. After 15 minutes, alcohol body (611mg
, 1.3 mmol) in anhydrous dichloromethane (2 ml
) was added over 5 minutes. After stirring for 1 hour, a solution of 5 equivalents of triethylamine (625 mg, 6.2 mmol) in anhydrous dichloromethane (2 ml) was added over 10 minutes. After 30 minutes, the reaction mixture was warmed from -78° to room temperature, water was added, extracted with dichloromethane, water (twice),
After washing with saturated brine (once), it was dried over anhydrous magnesium sulfate. The solvent was distilled off to obtain 622 mg of crude product. This was subjected to SiO2 column chromatography (developing solution
Separate with hexane: ethyl acetate = 50:1 → 3:1) to obtain the desired aldehyde (509 mg, 86.5%)
20 mg of recovered raw material was obtained.

[α]23D +25.6° (c=1.0, CHCl
3) IR (film) cm-1; 2950, 2870,
1692, 1432, 1120, 1080, 820, 7
40,700. NMR (CDCl3, 90MHz) δp
pm; 10.6 (s, 9H, -C(CH3)3), 1.
41, 1.61, 1.69 (each s, each 3H, = CC
H3), 1.9-2.4(m, 8H, -CH2CH2-
×2), 4.06 (bt, J=5.7Hz, 1H, -C
HO-), 4.73 (bs, 2H, =CH2), 4.8
9 (bm, 1H, =CH-), 5.83 (d, J = 7.
9Hz, 1H, = CHCHO), 7.3-7.7 (m,
10H, Ph), 9.97 (d, J=7.9Hz, 1H
, -CHO).

Synthesis Example 27

[Chemical formula 52] In a heat-dried 30 ml two-necked flask under an argon stream, 1
．． 7 equivalents of ethyl 2-(diethylphospho)isovalerate (1.0 g, 3.8 mmol) and 10 ml of anhydrous tetrahydrofuran were taken, and the mixture was cooled to -78° and stirred. 1.7
An equivalent amount of n-butyllithium (2.2 ml, 1.6M hexane solution) was added dropwise and stirred for 1.5 hours. Anhydrous tetrahydrofuran solution (1.5 ml) of the aldehyde (1.1 g, 2.2 mmol) was added dropwise thereto, and after 10 minutes,
When the cold bath was removed, the reaction mixture gradually changed from colorless to dark yellow. After stirring overnight at room temperature, disappearance of the raw materials was confirmed by TLC (hexane:ethyl acetate=20:1). 2 ml of water was slowly added to the reaction mixture, and after stirring for 10 minutes, the solvent was distilled off, water was added to the residue, extracted with ethyl acetate, and washed with water (once) and saturated brine (once). Afterwards, it was dried with anhydrous magnesium sulfate. The solvent was distilled off to obtain 1.7629 g of a yellow crude product. This was subjected to SiO2 column chromatography (developing solution: hexane: ethyl acetate = 5
0:1 → 20:1), and two types of diene Z forms (59
6 mg, 45.3%) and E form (351 mg, 126.7%
) was obtained (Z:E=1.7:1). The physical data of the target Z body is shown below.

[α]23D +24.4° (c=1.0, CHCl
3). IR (film) cm-1; 3060, 3045, 29
50, 2920, 2850, 1700, 1615, 14
10,1110,820,740,700. NMR (CDCl3, 90MHz) δppm; 1.09
(s, 9H, C(CH3)), 1.10 (d, J=6.
6Hz, 6H, -CH(CH3)2), 1.24(t,
J=6.9Hz, 3H, -CH2CH3), 1.57,
1.68, 1.79 (each s, each 3H, =CCH3)
,1.7-2.1(m,8H,-CH2CH2-),2
．． 80(hep, J=6.6Hz, 1H, -CH(CH
3)2),4.06(t,J=6.5Hz,1H,-C
HO-), 4.23 (q, J=6.9Hz, 2H, -C
H2CH3), 4.72(bs,2H,=CH2),4
．． 95 (bm, 1H, =CH-), 6.54 (bs, 2
H, =CH-HC=), 7.3-7.8 (m, 10H,
Ph).

Synthesis Example 28

embedded image Ester compound (110 mg, 0.19 mmol) and 2 ml of anhydrous toluene were placed in a heat-dried 30 ml two-necked flask under an argon stream and cooled to -78°. While stirring, add 2.2 equivalents of diisobutylaluminum hydride (0
．． 41ml, 1.0M toluene solution, 0.41mmol
) and stirred for 15 minutes, the disappearance of the raw materials was confirmed by TLC (hexane:ethyl acetate=10:1). The reaction mixture was returned to 0°C from -78°, 0.5 ml of water was gradually added dropwise, and the mixture was stirred at 0°C for 10 minutes. To this, ether 7m
1, Celite, and anhydrous magnesium sulfate were added, and the mixture was stirred for 20 minutes. Inorganic substances were removed by filtration, and the solvent was distilled off under reduced pressure to obtain 105 mg of a crude product. This was subjected to SiO2 column chromatography (developing solution
It was purified with hexane:ethyl acetate=20:1) to obtain the desired alcohol (96.8 mg, 94.8%).

[α]24D +23.7° (c=0.99, CHC
l3). IR (film) cm-1; 3300, 3070, 30
50, 2950, 2930, 2850, 1465, 14
60,1440,1413,1110,1060,10
00,820,740,700. NMR (CDCl3, 90MHz) δppm; 1.06
(s, 9H, C(CH3)3), 1.09 (d, J=7
．． 0Hz, 6H, -CH(CH3)2), 1.41, 1
．． 68.1.75 (each s, each 3H, =CCH3),
1.7-2.0 (m, 8H, -CH2CH2-), 2.
48(hep, J=7.0Hz, 1H, -CH(CH3
)2), 4.06 (t, J=6.4Hz, 1H, -CH
O-), 4.24 (s, 2H, -CH2OH), 4.7
2 (bs, 2H, = CH2), 4.94 (bm, 1H,
=CH-), 6.15 (bs, 2H, =CH-CH=)
, 7.1-7.8 (m, 10H, Ph).

[0081]
Synthesis example 29

embedded image The silyether compound (194 mg, 0.37 mmol) was added to 2 equivalents of tetra-n-butylammonium fluoride (0.73 ml) in anhydrous tetrahydrofuran solution (5 ml).
, 1.0M tetrahydrofuran solution) was added thereto, and the mixture was stirred at room temperature. The reaction mixture turned from colorless to red-orange. After 2 hours, TLC (hexane: ethyl acetate = 20:1)
Confirmed the disappearance of raw materials. The solvent was distilled off and extracted with ethyl acetate. The organic layer was washed with water (twice) and saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure,
218 mg of crude product was obtained. This was separated by SiO2 column chromatography to obtain the same diol compound (105 mg, 89%) as obtained in Synthesis Example 21.

Synthesis Example 30

embedded image Diols obtained in Synthesis Examples 21 and 29 (342 mg, 1.
To a solution of 12 mmol) in diethyl ether (1.5 ml) under an argon atmosphere on an ice-cooled bath, sodium hydride (7 mg) was added with stirring, and stirring was continued for an additional 2 hours, followed by addition of trichloroacetonitrile (162 mg,
A solution of 1.12 mmol) in ether (0.5 ml) was added all at once. After 30 min, the reaction mixture was concentrated and SiO2
Column chromatography (developing solution n-hexane:
Purified with ethyl acetate 6:1) to obtain monoimidate (327
mg, 65%) was obtained.

NMR (CDCl3, 250MHz) δp
pm; 1.08 (d, J=6.9Hz, 6H, -CH(
CH3)2),1.5-1.7(m,2H,=CCH2
CH2CH(OH)-), 1.59, 1.70 (each s
, each 3H, =CCH3×2), 1.76(d, J=1
．． 0Hz, 3H, =CCH3), 2.00(m, 2H,
=CCH2CH2CH(OH)-), 2.09(m, 4
H,=CCH2CH2C=),2.51(hep,J=
6.9Hz, 1H, -CH(CH3)2), 4.00(
t, J=6.3Hz, 1H, -CH(OH)), 4.8
0, 4.89 (each bs, each 1H, =CH2), 4.
88 (s, 2H, -CH2OC=NH), 5.12 (b
m, 1H, =CHCH2CH2-), 6.09 (bd,
J=11.4Hz, 1H, =CHa-HbC=), 6.
31 (d, J = 11.4Hz, 1H, = CHa-HbC
=), 8.26 (bs, 1H, =NH).

Example 1

embedded image Monotrichloromethylimidate (3
One drop of trichlorometalsulfonic acid was added to a solution of 61 mg, 0.8 mmol) in n-hexane under an argon atmosphere on a -78°C bath while stirring. After stirring at the same temperature for 1 hour, triethylamine was added for neutralization, and the residue obtained by distilling off the solvent under reduced pressure was subjected to SiO2 column chromatography (developing solution: n-hexane: ethyl acetate 20:1).
Subsequently, silver nitrate (7%)-SiO2 chromatography (
Developing solution n-hexane: ethyl acetate 10:1 → 6:1
) to obtain macrocyclic ether (34.4 mg, 15%)
I got it.

MS; 288 (M+), 259, 245,
203,175,151,136(BP),123,1
21,93(80%),68. NMR (CDCl3, 250MHz) δppm; 0.9
9, 1.01 (each d, J = 6.8Hz, each 3H, -
CH(CH3)2), 1.52, 1.65 (s each, 3H each, = CCH3 x 2), 1.75 (d, J = 1.0
Hz, 3H, = CCH3), 2.34 (hep, J = 6
．． 8Hz, 1H, -CH(CH3)2), 3.70(t
, J=5.8Hz, 1H, -CHOCH2-), 3.7
9, 3.88 (each d, J=11.3Hz, each 1H,
-CHOCHaHb-), 4.82(bs,2H,=C
H2), 5.10(bm, 1H, =CHCH2CH2-
), 5.98 (bd, J=11.0Hz, 1H,=CH
a-HbC=), 6.14 (d, J=11.0Hz, 1
H,=CHa-HbC=).

Example 2

embedded image The racemic epoxy compound obtained in Synthesis Example 10 was converted into Synthesis Example 16.
, 17, 21.
Diol compound (380 mg, 1.25 mmol) was dissolved in diethyl ether (13 ml) and sodium hydride (7
．． After stirring for 3 hours, a solution of trichloroacetonitrile (181 mg, 1.25 mmol) in diethyl ether (1 ml) was added with stirring. 1
After an hour, the remaining sodium hydride was removed by filtration, and the residue obtained by concentration under reduced pressure was immediately subjected to SiO2 column chromatography (developing solution: n-hexane: ethyl acetate 6:1) to obtain monoimidate (560 mg, 65%). Obtained. The spectrum data of monoimidate obtained here is Synthesis Example 3.
Same as the s-body obtained in 0.

The monoimidate content was dissolved in diethyl ether (100 ml) and one drop of trichloromethanesulfonic acid was added while stirring on a -78°C cold bath. After stirring at the same temperature for 1 hour, the residue obtained by adding triethylamine, neutralization, and concentration was subjected to SiO2 column chromatography (developing solution: n-hexane: ethyl acetate 20:1) to obtain a large amount of isomerized conjugated diene moiety. Cyclic ether (23
1 mg, 44%) was obtained.

MS; 288 (M+), 259, 245,
203,175,151,136(BP),123,1
21,93,68. NMR (CDCl3, 250MHz) δppm; 0.9
8, 1.04 (each d, J=7.0Hz, each 3H, -
CH(CH3)2), 1.60, 1.67, 1.83(
each s, each 3H, =CCH3×3), 1.5-2.3
(m, 8H, -CH2CH2×2), 2.92(hep
, J=7.0Hz, 1H, -CH(CH3)2), 3.
55, 4.03 (respectively d, J=13.8Hz, -CHa
HbO-), 3.81 (dd, J=4.4, 6.9Hz
, 1H, -CHO-), 4.83 (bs, 2H, =CH
2), 5.31 (bt, J=7.6Hz, 1H, =CH
-), 6.13, 6.16 (respectively bd, J=12Hz,
Each 1H, =CH-CH=).

Reference example 1

embedded image DL-macrocyclic ether (13.7 m
g, 0.048 mmol) in diethyl ether (1
．． 0.5 ml of a 1.5 M cyclohexane solution of tert-butyllithium was added dropwise to the solution (0.5 ml) of tert-butyllithium in cyclohexane under an argon atmosphere while stirring on a -78°C bath. Remove the bath, about 30 minutes
After raising the temperature to room temperature over a few minutes, the mixture was cooled again to -78°C and a small amount of water was added to stop the reaction. The residue obtained by drying and concentrating the organic layer was purified by SiO2 column chromatography (developing solution: n-hexane: ethyl acetate 8:1), and the behavior on various spectral data, TLC, GC, and HPLC was determined to be sarcophytol A. Alcohol body (12.0m
g, 68%) was obtained.

Reference example 2

embedded image Macrocyclic ether obtained in Example 2 (47 mg, 0.16
A reaction was carried out in the same manner as in Reference Example 1 using a solution of 3 mmol) in tetrahydrofuran (3 ml) to obtain an alcohol compound (46 mg, 97 mmol) whose spectral data matched that of sarcophytol T.
%) was obtained. The NMR data of the racemic alcohol obtained is listed below. NMR (CDCl3, 250MHz) δppm; 1.0
8, 1.17 (each d, J = 7.2Hz, each 3H, -
CH(CH3)2), 1.55, 1.57 (each s, each 3H, = CH3), 1.81 (d, J = 1.2Hz,
3H,=CH3), 1.8-2.5(m, 10H, -C
H2CH2-×2, -CH2CHOH-), 2.88(
hep, J=7.2Hz, 1H, -CH(CH3)2)
, 4.33 (dd, J=4.0, 10.0Hz, 1H,
-CHOH-), 4.94 (bt, J=7.5Hz, 1
H,=CH), 4.97(bt, J=6.8Hz, 1H
, =CH-), 6.04 (d, J=18.8Hz, 1H
, =CHa-CHb=), 6.22 (bd, J=18.
8Hz, 1H, = CHa-Hb)

[0091]

EFFECTS OF THE INVENTION The compounds of the present invention are extremely important as intermediates for the synthesis of sarcophytol A and its stereoisomers, which have anti-carcinogenic promoter activity and anti-tumor activity.

Claims (1)

[Claims] Claim 1: General formula (I) [Image Omitted] represents the configuration of Z or E. ), and * represents an asymmetric carbon atom).