JPH06321850A - (2s,4ar,6s,8s,8as)-1,2,4a,5,6,7,8,8a-octahydro-2methyl-6-substituted alkenynaphthalene derivative - Google Patents

Abstract

PURPOSE:To obtain a new compound useful as a raw material for producing HMG-CoA reductase inhibitor. CONSTITUTION:A compound of formula I [R<1> is oxycarbonyl of COOR<4> (R<4> is H, 1-5C alkyl, aryl, etc) or oxymethyl of CH2OR<5> (R<5> is H or OH-protecting group); R<2> is H or OH-protecting group; R<3> is oxycarbonyl of COOR<6> (R<6> is H, 1-5C alkyl, aralkyl, etc.) or oxymethyl of CH2OR<7> (R<7> is H or OH-protecting group)] such as (1S,2S,4aR,6S,8S,8aS)-1,2,4a,5,6,7,8,8a-octahydro-1 ethocycarbonyl-6-[2-(ethoxycarbonyl)-(E)-ethynyl]-8-hydroxy-2-methylna phthalene. The compound of formula I is obtained by subjecting an octahydronaphthalenecarboaldehyde derivative of formula II as a starting substance to Wittig reaction, reduction, deprotection, etc., to give a triol of formula III and protecting the whole hydroxyl groups of the triol.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION Industrial field (2S, 4aR, 6S,
8S, 8aS) -1,2,4a, 5,6,7,8,8a
The -octahydro-2-methyl-6-substituted alkenylnaphthalene derivative has the following formula (1)

[0002]

[Chemical 2]

In the synthesis of the HMG-CoA reductase inhibitor represented by the following formula (2)

[0004]

[Chemical 3]

A key synthesis intermediate [[1S, 3S,
4aR, 7S, 8S, 8aS) -1, 2, 3, 4, 4
a, 7,8,8a-Octahydro-8- (hydroxymethyl) -7-methyl-3-[(E) -1-propenyl]
-1-Naphthalenyl 2,2-dimethylbutyrate] (C.
M. Blackwell, et al., J. Org. Chem., 57, 5596 (1992), A.
H. Davidson, et al., J. Chem. Soc., Chem. Commun., 1786
(1987) and AH Davidson, et al., J. Chem. Soc., Che.
m.Commun., 1662 (1985)).

[0006]

2. Description of the Related Art Conventionally, HMG-CoA represented by the above formula (2)
A key synthetic intermediate of a reductase inhibitor compound is a compound represented by the following formula (4) by reacting an aldehyde represented by the formula (3) with 1,1-diiodoethane in the presence of a large excess of chromium (II) chloride. Was produced by selectively reducing the ethoxycarbonyl group after forming the (E) -propenylated compound represented by the formula (CMBlackwell, et al., J.Or).
g. Chem., 57, 5596 (1992)). However, this synthetic method requires extremely large amounts of chromium (II) chloride, which is extremely toxic and expensive, and could not be industrially implemented at all.

[0007]

[Chemical 4]

[0008]

DISCLOSURE OF THE INVENTION The present inventors have made the following general formula (5)

[0009]

[Chemical 5]

[In the formula, R ¹ is an oxycarbonyl group represented by COOR ⁴ (R ⁴ is a hydrogen atom, a linear or branched lower alkyl group having 1 to 5 carbon atoms, a substituted or unsubstituted aralkyl Group, or a substituted or unsubstituted aryl group) or an oxymethyl group represented by CH ₂ OR ⁵ (R ⁵ represents a hydrogen atom or a hydroxyl-protecting group), and R ² represents a hydrogen atom or a hydroxyl group. Represents a protecting group, R ³ represents an oxycarbonyl group represented by COOR ⁶ (R ⁶ represents a hydrogen atom, a linear or branched lower alkyl group having 1 to 5 carbon atoms, a substituted or unsubstituted aralkyl group, Or a substituted or unsubstituted aryl group) or CH ₂ OR ⁷
Represents an oxymethyl group (R ⁷ represents a hydrogen atom or a hydroxyl-protecting group)] (2S, 4a
R, 6S, 8S, 8aS) -1,2,4a, 5,6
The 7,8,8a-octahydro-2-methyl-6-substituted alkenylnaphthalene derivative is represented by the formula (2).
The present invention has been completed by finding that it is very useful as a raw material for producing a G-CoA reductase inhibitor.

[0011]

[Means for Solving the Problems] (2S, 4aR, 6S, 8S, 8aS) -1, 2, 4 represented by the formula (5).
The a, 5,6,7,8,8a-octahydro-2-methyl-6-substituted alkenylnaphthalene derivative can be easily synthesized by the following synthesis steps.

[0012]

[Chemical 6]

[0013]

[Chemical 7]

[0014] [wherein, R ^{2 'represents} a protecting group for a hydroxyl group, R
⁴ is a hydrogen atom, a linear or branched lower alkyl group having 1 to 5 carbon atoms, a substituted or unsubstituted aralkyl group,
Or a substituted or unsubstituted aryl group, R ⁶ is a hydrogen atom, a linear or branched lower alkyl group having 1 to 5 carbon atoms, a substituted or unsubstituted aralkyl group, or a substituted or unsubstituted aryl R ⁷ represents a hydrogen atom or a hydroxyl group-protecting group. ]

[First Step] In this step, the octahydronaphthalenecarbaldehyde derivative represented by the general formula (6) (see Reference Examples 1, 2 and 3 below) is subjected to Wittig reaction using a stable ylide. Thus, the 6- [2- (oxycarbonyl)-(E) -ethenyl] -8-hydroxyoctahydronaphthalene derivative represented by the general formula (7), which is the compound of the present invention, is produced.

The stable ylide used in this step is (carboethoxymethylene) triphenylphosphorane,
(Carbomethoxymethylene) triphenylphosphorane,
[Carbo (n-propoxy) methylene] triphenylphosphorane, [carbo (i-propoxy) methylene] triphenylphosphorane, [carbo (n-butoxy) methylene] triphenylphosphorane, [carbo (i-butoxy) methylene ] Triphenylphosphorane, [carbo (s
-Butoxy) methylene] triphenylphosphorane, [carbo (t-butoxy) methylene] triphenylphosphorane, [carbo (n-pentyloxy) methylene] triphenylphosphorane, [carbo (neopentyloxy) methylene] triphenyl Phospholane, (carbophenoxymethylene) triphenylphosphorane, [carbo (p-methylphenoxy) methylene] triphenylphosphorane,
[Carbo (p-chlorobenzylphenoxy) methylene]
Triphenylphosphorane, [carbo (p-methoxyphenoxy) methylene] triphenylphosphorane, [carbo (p-nitrophenoxy) methylene] triphenylphosphorane, [carbo (2,4-dichlorophenoxy) methylene] triphenylphospho Orchid, [carbo (2,4-dimethylphenoxy) methylene] triphenylphosphorane, [carbo (3,5-dichlorophenoxy) methylene] triphenylphosphorane, [carbo (p-methylbenzyloxy) methylene] triphenylphosphorane run,
[Carbo (p-chlorobenzylbenzyloxy) methylene] triphenylphosphorane, [carbo (p-methoxybenzyloxy) methylene] triphenylphosphorane,
[Carbo (p-nitrobenzyloxy) methylene] triphenylphosphorane, [carbo (2,4-dichlorobenzyloxy) methylene] triphenylphosphorane, [carbo (2,4-dimethylbenzyloxy) methylene] triphenylphosphorane Examples thereof include lan and [carbo (3,5-dichlorobenzyloxy) methylene] triphenylphosphorane, and (carboethoxymethylene) triphenylphosphorane is preferably used.

This reaction is carried out in a solvent, and any reaction solvent can be used as long as it does not participate in the reaction, but alcohol solvents such as methanol, ethanol, propanol, isopropyl alcohol, t-butanol, and tetrahydrofuran. Ether solvents such as dioxane and 1,2-diethoxyethane, polar solvents such as dimethylformamide, dimethylacetamide and dimethylsulfoxide, halogen solvents such as dichloromethane, chloroform, dichloromethane, carbon tetrachloride and 1,2-dichloroethane, Petroleum ether, ligroin, pentane,
Hydrocarbon type solvents such as hexane, benzene, toluene, xylene and mesitylene can be exemplified, but halogen type solvents are preferably used, and dichloromethane is more preferably used. The reaction is carried out at -90 ° C to 100 ° C, preferably -20 ° C to 30 ° C.

[Second Step] In this step, the secondary hydroxyl group of the 6- [2- (oxycarbonyl)-(E) -ethenyl] -8-hydroxyoctahydronaphthalene derivative represented by the general formula (7) is converted. 6- [2- (oxycarbonyl) -represented by the general formula (8), which is a compound of the present invention, which is protected.
(E) -ethenyl] -8-oxyoctahydronaphthalene derivative is produced.

As the protecting group used in this step, those which are stable in the reduction reaction in the third step and can be easily removed thereafter without damaging other parts of the molecule are used. Examples of the hydroxyl-protecting group satisfying such conditions include a methyl group, a methoxymethyl group, a 2-methoxyethoxymethyl group, a benzyloxymethyl group, a 4-methoxybenzyl group, a triphenylmethyl group, a methylthiomethyl group and a tetrahydropyranyl group. Group, substituted methyl group such as allyl group, 1-ethoxyethyl group, t-butyl group, 2,2
Substituted ethyl group such as 2-trichloroethyl group, trimethylsilyl group, t-butyldimethylsilyl group, substituted silyl group such as t-butyldiphenylsilyl group, formyl group,
Acyl group such as acetyl group, trichloroacetyl group, pivaloyl group, benzoyl group, mesitoyl group, p-methoxybenzoyl group, aroyl group such as naphthoyl group, methoxycarbonyl group, allyloxycarbonyl group, benzyloxycarbonyl group, phenoxycarbonyl group Alkyl, aryl, and aralkyloxycarbonyl group, phenylaminocarbonyl group, and other alkyl, aryl, aralkylaminocarbonyl group, methanesulfonyl group, phenylsulfonyl group, p-toluenesulfonyl group, and other alkyl, aryl, and aralkylsulfonyl groups. Although illustrated, 1-ethoxyethyl group is preferably used. The conditions for introducing the protecting group depend on the type of protecting group used and are known methods [T. W. Green, et a
l. , "Protective Groups in
Organic Synthesis ”, John-W
iley & Sons, New York, 199
1, pp10-174], but when the protecting group is a 1-ethoxyethyl group, it is preferably carried out at 0 ° C to 30 ° C in dichloromethane using pyridinium p-toluenesulfonate as an acid catalyst. Be seen.

[Third step] In this step, two carboxyl groups of the 6- [2- (oxycarbonyl)-(E) -ethenyl] -8-oxyoctahydronaphthalene derivative represented by the general formula (8) are used. After reduction, the protective group for the hydroxyl group is removed to produce the triol represented by the compound (9) of the present invention.

As the reducing agent used in this step, sodium borohydride, lithium borohydride, lithium triethylborohydride, lithium tri-s-butylborohydride, sodium tri-s-butylborohydride, potassium tri-s-butyl. Examples thereof include borohydride, potassium trisiamylborohydride, sodium bis (2-methoxyethoxy) aluminum hydride, diisobutylaluminum hydride, lithium aluminum hydride, and the like, and diisobutylaluminum hydride is preferably used. The reaction is carried out in a solvent, and as the solvent used, aromatic solvents such as benzene, toluene, p-xylene, o-xylene, m-xylene, mesitylene and chlorobenzene, ether, tetrahydrofuran, dioxane, 1,2-diethoxyethane. Examples thereof include ether solvents such as, and halogen solvents such as chloroform, dichloromethane, carbon tetrachloride, and dichloroethane, but toluene is preferable. The reaction is carried out at -90 ° C to 100 ° C, preferably -30 ° C.
To 30 ° C.

Removal of the hydroxyl-protecting group is carried out by a known method [T. W. Green
n, et al. , "Protective Gro
upsin Organic Synthesis ”,
John-Wiley & Sons, New Yo
rk, 1991, pp10-174], but when the protective group is a 1-ethoxyethyl group, hydrochloric acid, nitric acid, sulfuric acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid or the like is used. The removal of the protecting group is carried out in a solvent, and as the solvent used, alcohol solvents such as methanol, ethanol, propanol, isopropyl alcohol, butanol, t-butanol are preferably used. The reaction proceeds smoothly at -20 ° C to 50 ° C.

[Fourth Step] In this step, all the hydroxyl groups of the triol represented by the formula (9) are protected to produce an octahydronaphthalene derivative represented by the general formula (10) which is a compound of the present invention. To do.

As the protective group used in this step, the carbon-oxygen bond at the allylic position is efficiently reductively cleaved in the reduction reaction in the next fifth step, and the other two protective groups are stably present. If necessary, a substance that can be easily removed without impairing other portions of the molecule is used. Examples of the hydroxyl-protecting group satisfying such conditions include a methyl group, a methoxymethyl group, a 2-methoxyethoxymethyl group, a benzyloxymethyl group, a 4-methoxybenzyl group, a triphenylmethyl group, a methylthiomethyl group and a tetrahydropyranyl group. Group, substituted methyl group such as allyl group, 1-ethoxyethyl group, t-butyl group, substituted ethyl group such as 2,2,2-trichloroethyl group, trimethylsilyl group, t-butyldimethylsilyl group, t-butyldiphenyl Substituted silyl group such as silyl group, formyl group, acetyl group, trichloroacetyl group, acyl group such as pivaloyl group, benzoyl group, mesitoyl group, p-methoxybenzoyl group, aroyl group such as naphthoyl group, methoxycarbonyl group, allyloxy Carbonyl group, benzyloxycarbonyl group,
Alkenyl such as phenoxycarbonyl group, and alkyl such as aralkyloxycarbonyl group, phenylaminocarbonyl group, aryl, aralkylaminocarbonyl group, methanesulfonyl group, phenylsulfonyl group, alkyl such as p-toluenesulfonyl group, aryl, aralkyl A sulfonyl group is exemplified, but a 1-ethoxyethyl group is preferably used. The conditions for introducing the protecting group depend on the type of protecting group used and are known methods [T. W. Green, et al. , "Protec
live Groups in Organic Sy
n'thesis ”, John-Wiley & Son
s, New York, 1991, pp10-17.
4], but when the protecting group is a 1-ethoxyethyl group, preferably pyridinium is used as the acid catalyst.
It is carried out in dichloromethane with p-toluenesulfonate at 0 ° C to 30 ° C.

The octahydronaphthalene derivative represented by the formula (10) of the present invention synthesized by the above steps is
The compound represented by the above formula (2), which is a key synthetic intermediate of the HMG-CoA reductase inhibitor, is derived by the following synthetic steps.

[0026]

[Chemical 8]

[Fifth Step] In this step, the carbon at the allylic position of the octahydronaphthalene derivative represented by the formula (10) is used.
It is represented by the formula (11) which can be easily derived to the key synthetic intermediate represented by the above formula (2) by reductively cleaving the oxygen bond and removing the remaining two hydroxyl protecting groups (1
S, 2S, 4aR, 6S, 8S, 8aS) -1, 2, 4
a, 5,6,7,8,8a-octahydro-8-hydroxy-1-hydroxymethyl-2-methyl-6-
[(E) -1-propenyl] naphthalene is produced.

As a reduction method, lithium naphthalene,
Reduction with metal naphthalene such as sodium naphthalene, potassium naphthalene or lithium metal in liquid ammonia, ethylamine or ethylenediamine,
Illustrate reduction with alkali and alkaline earth metals such as metallic sodium, metallic potassium, calcium, magnesium, etc., reduction with zinc dust, tin or tin chloride in acetic acid or dilute hydrochloric acid, reduction with Raney nickel, electrolytic reduction, etc. However, preferably the reduction is carried out in an alkylamine or ammonia with an alkali metal, more preferably in liquid ammonia with metallic lithium. The reaction solvent is appropriately selected depending on the reduction method, but in the case of reduction using metallic lithium in liquid ammonia, a mixed solvent system can be used, and the solvent to be mixed is ethanol, propanol, isopropyl alcohol, t-butanol. Alcohol solvents such as tetrahydrofuran, dioxane, 1,2-
Examples include ether solvents such as diethoxyethane, polar solvents such as dimethylformamide and dimethylacetamide, and hydrocarbon solvents such as pentane and hexane, but ether solvents are more preferable, and tetrahydrofuran is more preferable. The reaction temperature is appropriately selected depending on the reduction method, but in the case of reduction using metallic lithium in liquid ammonia, it is preferably carried out at -33 ° C (boiling point of liquid ammonia).

Removal of the hydroxyl-protecting group is carried out by a known method [T. W. Green
n, et al. , "Protective Gro
upsin Organic Synthesis ”,
John-Wiley & Sons, New Yo
rk, 1991, pp10-174], but when the protective group is a 1-ethoxyethyl group, hydrochloric acid, nitric acid, sulfuric acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid or the like is used. The removal of this protective group is carried out in a solvent, and as the solvent used, alcohol solvents such as methanol, ethanol, propanol, isopropyl alcohol, butanol, t-butanol are preferably used. The reaction proceeds smoothly at -20 ° C to 50 ° C.

[Sixth Step] This step is represented by the formula (11) (1S, 2S, 4aR, 6S, 8S, 8aS)-
1,2,4a, 5,6,7,8,8a-octahydro-
8-hydroxy-1-hydroxymethyl-2-methyl-
After the primary hydroxyl group of 6-[(E) -1-propenyl] naphthalene is protected, the secondary hydroxyl group is converted to 2,2-dimethylbutyryl, and the protective group of the hydroxyl group is removed to obtain the compound represented by the formula (2). (1S, 3S, 4aR, 7S, 8S,
8aS) -1,2,3,4,4a, 7,8,8a-octahydro-8- (hydroxymethyl) -7-methyl-3
-[(E) -1-propenyl] -1-naphthalenyl
2,2-Dimethylbutyrate (CMBlackwell, et al.,
J. Org. Chem., 57, 5596 (1992)).

[0031]

The present invention is described in detail below with reference to examples and reference examples, but it goes without saying that the present invention is not limited to these.

Reference Example 1

[0033]

[Chemical 9]

(3S, 5S) -3- [2 ′ (E), 4 ′ (E) -hexadienyl]
-5-Hydroxymethyltetrahydrofuran-2-one (1.57
g, 8.0 mmol) (CMBlackwell, et al., J.Org.Chem., 5
7, 5596 (1992), AHDavidson, et al., J. Chem. Soc., Ch
em.Commun., 1786 (1987) and AHD Davidson, et al.,
CH ₂ Cl from J. Chem. Soc., Chem. Commun., 1662 (1985)).
_{2 To the} (16 mL) solution, add 1.0 M DIBAL in hexane (17.6 mL).
Added at -35 ° C. After stirring at the same temperature for 20 minutes, the reaction mixture was poured into 2 M hydrochloric acid (40 mL) to terminate the reaction. The organic layer was separated, extracted twice with CH ₂ Cl ₂ (20 mL), the organic layers were combined and dried over magnesium sulfate. The desiccant was filtered off and the solvent was distilled off.The residue was dissolved in methanol (14 mL) and
-Toluenesulfonic acid monohydrate (50 mg) was added and
Stir for hours. The reaction mixture was concentrated under reduced pressure, ethyl acetate 5
0 mL was added, and the mixture was washed successively with saturated aqueous sodium hydrogen carbonate (30 mL) and saturated brine (30 mL). The organic layer was dried over magnesium sulfate, the desiccant was filtered off and the residue obtained by concentration under reduced pressure was purified by column chromatography (hexane: ethyl acetate, 3: 1-2: 1), (2RS, 3S, 5S) -3- [2 '(E), 4' (E) -hexadienyl] -5-
Hydroxymethyl-2-methoxytetrahydrofuran (1.32
g, 78%) was obtained as a colorless oil. This was a 2: 1 mixture of diastereomers based on stereoisomerism at the 2-position. Boiling point 120-130 ℃ / 0.75 mmHg

¹ H NMR (mixture of two diastereomers,
CDCl ₃ , 200 MHz) δ 1.36 (0.67x1H, m), 1.66 (0.33x1)
H, m), 1.74 (3H, d, J = 6.2 Hz), 1.82-2.34 (5H,
m), 3.34 (0.67x3H, s), 3.39 (0.33x 3H, s), 3.44-
3.61 (2H, m), 3.68-3.85 (2H, m), 4.15-4.38 (1H, s),
4.69 (0.67x1H, d, J = 1.4 Hz), 4.75 (0.33x1H,
d, J = 3.8 Hz), 5.40-5.69 (2H, m), 5.93-6.12 (2H,
m) IR (neat) 3430, 2900, 1445, 1100, 1060, 1020, 980
cm ^-1 MS (low resolution) 212 (M ⁺ ), 180, 143 MS (high resolution) Measured value 212.1433, Calculated value (C ₁₂ H ₂₀ O ₃ ) 21
2.1411 [α] ²⁰ _D +27.0 ^o (c 1.14, CHCl ₃ ).

Reference Example 2

[0037]

[Chemical 10]

(2RS, 3S, 5S) -3- [2 ′ (E), 4 ′ (E) -hexadienyl] -5-hydroxymethyl consisting of a mixture of 2: 1 isomers based on the stereoisomerism at the 2-position 2-Methoxytetrahydrofuran (1.06 g, 5.0 mmol) was dissolved in triethylamine (5.3 mL), and sulfur trioxide pyridine complex (2.
A solution of 38 g, 15 mmol) in dimethylsulfoxide (10.6 mL) was added at room temperature. After stirring for 30 minutes, triethylphosphonoacetate (1.68 g, 7.50 mmol) and aqueous potassium carbonate solution (7.00
(g / 14.0 mL) were added sequentially, and the mixture was stirred at room temperature for 3 hours. Ligroin (70 mL) was added to the reaction mixture, and the mixture was washed successively with water, 2 N hydrochloric acid, saturated brine and 70 mL. The organic layer was dried over MgSO ₄ ,
Column chromatography of the residue obtained by concentration under reduced pressure
Purify with (hexane: ethyl acetate, 18: 1) to consist of a mixture of 2: 1 isomers based on the stereochemistry at the 2-position (2RS, 3S,
5S) -3- [2 '(E), 4' (E) -hexadienyl] -5- [2- (ethoxycarbonyl)-(E) -ethenyl] -2-methoxytetrahydrofuran (1.28 g, 91%) Obtained as a colorless oil.

¹ H NMR (mixture of two diastereomers,
CDCl ₃ , 200 MHz) δ 1.29 (3H, t, J = 7.1 Hz), 1.34
(1H, m), 1.73 (3H, d, J = 6.2 Hz), 2.04-2.39 (4H,
m), 3.35 (0.67x3H, s), 3.39 (0.33x 3H, s), 4.20
(2H, q, J = 7.1 Hz), 4.57-4.75 (1H, m), 4.75 (0.67
x1H, d, J = 1.2 Hz), 4.80 (0.33x1H, d, J = 3.5 Hz),
5.36-5.70 (2H, m), 5.93-6.09 (3H, m), 6.92 (0.33x
1H, dd, J = 15.6, 6.1Hz), 6.94 (0.67x1H, dd, J =
15.7, 5.3 Hz) IR (neat) 2920, 1720, 1660, 1300, 1260, 1100, 980 c
m ^-1 MS (low resolution) 280 (M ⁺ ), 248, 234, 220, 207, 122 MS (high resolution) measured value 280.1674, calculated value (C ₁₆ H ₂₄ O ₄ ) 280.
1673 [α] ²⁰ _D -2.8 ^o (c 0.99, CHCl ₃ )

Reference Example 3

[0041]

[Chemical 11]

(2RS, 3S, 5S) -3- [2 ′ (E), 4 ′ (E) -hexadienyl] consisting of a mixture of 2: 1 isomers based on the 2-position steric
-5- [2- (Ethoxycarbonyl)-(E) -ethenyl] -2-methoxytetrahydrofuran (280 mg, 1.0 mmol) was added to mesitylene.
It was dissolved in (2.8 mL) and heated in a sealed tube at 165 ° C. for 90 hours. The crude (1S, 2S, 3S, 4S, 7R, obtained by concentrating the reaction mixture,
9S) -3-Ethoxycarbonyl-10-methoxy-4-methyl-11-
Oxa-5-tricyclo [7.2.1.0 ^2,7 ] undecene was added to THF (2.8
The mixture was dissolved in 1 mL), 1N hydrochloric acid (0.5 mL) was added under ice cooling, and the mixture was stirred at room temperature for 8 hours. Saturated aqueous sodium hydrogen carbonate (30 mL) was added to the reaction mixture, and the mixture was extracted 3 times with chloroform (20 mL). The organic layers were combined and dried over magnesium sulfate. The desiccant was filtered off and the residue obtained by concentration under reduced pressure was purified by column chromatography (hexane: ethyl acetate = 2: 1) (1S, 2S, 4aR, 6
S, 8S, 8aS) -1,2,4a, 5,6,7,8,8a-octahydro-1-ethoxycarbonyl-6-formyl-8-hydroxy-2-methylnaphthalene (200 mg, 2 steps Yield 75%) was obtained as colorless crystals. This is an equilibrium mixture with the corresponding lactol in CDCl ₃ (hydroxyaldehyde form: lactol form =
0.75: 0.25) was shown by ¹ H-NMR. However, since the melting point width is small in the crystalline state and CH stretching vibration (2730 cm ^-1 ) of the aldehyde is observed in the IR (KBr) spectrum, it is considered that the structure is exclusively hydroxyaldehyde. mp. 97-99 ° C (hexane-ethyl acetate)

¹ H NMR (CDCl ₃ , 400 MHz) δ 0.87 (0.25
x3H, d, J = 7.2 Hz), 0.91 (0.75x3H, d, J = 7.1 H
z), 1.27 (3H, t, J = 7.1 Hz), 1.19-1.60 (2H, m),
1.78 (0.25x1H, m), 1.89 (0.75x1H, ddd, J = 2.9, 6.
5, 14.9 Hz), 2.11-2.41 (3H, m), 2.17 (0.75x1H, br
d, J = 4.1 Hz), 2.48 (0.25x1H, br d, J = 4.8Hz),
2.57-2.67 (2H, m), 2.78 (0.25x1H, dd, J = 6.6, 11.
7 Hz), 2.79 (0.75x1H, dd, J = 5.8, 11.5 Hz), 4.10-
4.21 (2H, m), 4.32 (0.75x1H, br s), 4.65 (0.25x1H,
d, J = 6.2 Hz), 5.20 (0.25x1H, d, 4.7 Hz), 5.41-5.
48 (1H + 0.25x1H, m), 5.58 (0.75x1H, ddd, J = 2.7,
4.6, 9.8 Hz), 9.77 (0.75x1H, s) IR (KBr) 3520, 2910, 2730, 1720, 1170, 1130 cm ^-1 Analysis C ₁₅ H ₂₂ O ₄ : Calculated value C, 67.65; H, 8.33.Measurement Value C,
67.42; H, 8.33. [Α] ²⁰ _D +190 ^o (c 0.98, CHCl ₃ ).

Example 1

[0045]

[Chemical 12]

(1S, 2S, 4aR, 6S, 8S, 8aS) -1,2,4a, 5,6,7,8,8
a-Octahydro-1-ethoxycarbonyl-6-formyl-8-
Hydroxy-2-methylnaphthalene (1.84 g, 6.9 mmol) was dissolved in dichloromethane (20 mL), and carboethoxymethylene triphenylphosphorane (2.89 g, 8.30 mmo) under ice cooling.
l) was added and the mixture was stirred at the same temperature for 1 hour and at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure to 1/3 volume and filtered through silica gel (hexane: ethyl acetate = 2: 1). By concentrating the filtrate under reduced pressure (1S, 2S, 4aR, 6S, 8S, 8aS) -1,2,
4a, 5,6,7,8,8a-octahydro-1-ethoxycarbonyl-6-
[2- (ethoxycarbonyl)-(E) -ethenyl] -8-hydroxy
2-Methylnaphthalene (2.23 g, 96%) was obtained as a colorless oily substance.

¹ H NMR (CDCl ₃ , 400 MHz) δ 0.93 (3H,
d, J = 7.1 Hz), 1.26 (3H, t, J = 7.2 Hz), 1.28 (3H, t,
J = 7.2 Hz), 1.45 (1H, dt, J = 5.0, 13.3 Hz), 1.57 (1
H, dt, J = 2.2, 11.3 Hz), 1.84-2.01 (3H, m), 2.50 (1
H, m), 2.63 (1H, m), 2.70 (1H, m), 2.85 (1H, dd, J
= 5.9, 11.6 Hz), 4.15 (2H, m), 4.18 (2H, q, J = 7.1 H
z), 4.35 (1H, diffused d, J = 2.4Hz), 5.40 (1H, diff
used d, J = 9.9 Hz), 5.59 (1H, ddd, J = 2.7, 4.6, 9.8
Hz), 5.84 (1H, dd, J = 1.7, 15.8 Hz), 7.38 (1H, dd,
J = 7.1, 15.8 Hz) IR (neat) 3500, 2920, 1720, 1640, 1370, 1260, 1240,
1170, 1130, 1040 cm ^-1 MS (EI, low resolution) 336 (M ⁺ ), 318, 290, 272, 245, 199,
145 [α] ²⁰ _D +130 ^o (c 2.35, CHCl ₃ )

Example 2

[0049]

[Chemical 13]

(1S, 2S, 4aR, 6S, 8S, 8aS) -1,2,4a, 5,6,7,8,8
a-Octahydro-1-ethoxycarbonyl-6- [2- (ethoxycarbonyl)-(E) -ethenyl] -8-hydroxy-2-methylnaphthalene (632 mg, 1.88 mmol) in dichloromethane (10 mL)
Pyridinium p-toluenesulfonate (25
mg, 0.10 mmol) and ethyl vinyl ether (302 mg, 4.2
(mmol) was sequentially added under ice cooling, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with ethyl acetate (50 mL) and saturated aqueous sodium hydrogen carbonate (50
(mL) and saturated brine (50 mL), and then dried over magnesium sulfate. The residue obtained by concentration under reduced pressure was subjected to column chromatography (hexane: ethyl acetate = 10: 1 to 1: 1).
(1S, 2S, 4aR, 6S, 8S, 8aS)-
1,2,4a, 5,6,7,8,8a-octahydro-1-ethoxycarbonyl-6- [2- (ethoxycarbonyl)-(E) -ethenyl] -8- (1-ethoxyethoxy) -2 -Methylnaphthalene (757 mg, 99%) was obtained as a colorless oily substance. It was an approximately 1 to 1 mixture of binary diastereomers based on the 1-ethoxyethoxy group at the 8-position.

¹ H NMR (mixture of two isomers, CDCl ₃ , 20
0 MHz) δ 0.88 (0.5x3H, d, J = 6.9Hz), 0.90 (0.5x3
H, d, J = 6.9 Hz), 1.10 (0.5x3H, t, J = 7.0 Hz), 1.13
(0.5x3H, t, J = 7.0 Hz), 1.22 (0.5x3H, d, J = 5.3 Hz),
1.23 (0.5x3H, t, J = 7.0 Hz), 1.25-1.30 (6H, m), 1.3
8-1.48 (1H, m), 1.52-1.63 (1H, m), 1.70 (0.5x1H, dd
d, J = 2.5, 5.9, 14.8 Hz), 1.76-1.84 (0.5x1H + 1H,
m), 2.08 (1H, m), 2.46-2.64 (2H, m), 2.69 (1H, m),
2.82 (0.5x1H, dd, J = 6.1, 11.6 Hz), 2.94 (0.5x1H,
dd, J = 6.1, 11.7 Hz), 3.35 (0.5x1H, dq, J = 9.3, 7.0
Hz), 3.42-3.55 (0.5x1H + 1H, m), 4.03-4.25 (0.5x1H
+ 4H, m), 4.29 (0.5x1H, diffused d, J = 2.4 Hz), 4.50
(0.5x1H, q, J = 5.3 Hz), 4.63 (0.5x1H, q, J = 5.3 H
z), 5.37 (1H, diffused d, J = 9.9 Hz), 5.56-5.61 (1H,
m), 5.75 (0.5x1H, dd, J = 1.2,15.7 Hz), 5.79 (0.5x1
H, dd, J = 1.2, 15.7 Hz), 7.31 (0.5x1H, dd, J = 8.4, 1
5.7 Hz), 7.49 (0.5x1H, dd, J = 8.5, 15.7 Hz) IR (neat) 2970, 2920, 1720, 1380, 1250, 1160, 1130,
1090, 1030 cm ^-1 MS (mixture of two isomers, SIMS (NBA, NaCl), low resolution)
431 (M ⁺ + Na), 319, 245,199 [α] ²⁰ _D +202 ^o (mixture of two isomers, c 0.63, CHCl ₃ ).

Example 3

[0053]

[Chemical 14]

(1S, 2S, 4aR, 6S, 8S, 8aS) -1,2,4a, 5,6,7,8,8
a-Octahydro-1-ethoxycarbonyl-6- [2- (ethoxycarbonyl)-(E) -ethenyl] -8- (1-ethoxyethoxy) -2
Approximately 1: 1 mixture of binary diastereomers based on the 1-ethoxyethoxy group at the 8-position of -methylnaphthalene (757 m
g, 1.9 mmol) in toluene (10 mL), and a solution of diisobutylaluminum hydride in toluene (1.02 mol / L,
7.1 mL, 7.2 mmol) was added at -30 ° C, and the mixture was stirred at the same temperature for 30 minutes. The reaction was stopped by adding hydrochloric acid (1 mol / L, 60 mL), and the mixture was extracted with ethyl acetate (30 mL). The organic layer was saturated brine (30 mL)
It was washed with and dried over magnesium sulfate. The residue obtained by concentration under reduced pressure was dissolved in methanol (10 mL), p-toluenesulfonic acid (30 mg, 0.16 mmol) was added, and the mixture was stirred at room temperature for 30 min. The reaction mixture was concentrated under vacuum to 1/4 volume,
The mixture was diluted with ethyl acetate (40 mL), washed successively with saturated aqueous sodium hydrogen carbonate (30 mL) and saturated brine (30 mL), and dried over magnesium sulfate. The solid residue obtained by concentration under reduced pressure was crushed in a mixed solvent of toluene and hexane (1: 1) and collected by filtration to obtain (1S, 2S, 4aR, 6S, 8S, 8aS) -1,2, 4a, 5,6,7,8,8a-octahydro-8-hydroxy-1-hydroxymethyl-6-[(E) -1-
(3-Hydroxypropenyl)]-2-methylnaphthalene (389 m
g, 83%) was obtained as colorless crystals.

Mp. 138-140 ° C (toluene-hexane) ¹ H NMR (CDCl ₃ -D ₂ O, 400 MHz) δ 0.81 (3H, d, J = 7.0)
Hz), 1.22 (1H, dt, J = 2.4, 10.9 Hz), 1.34 (1H, dt,
J = 4.8, 13.2 Hz), 1.77 (1H, m), 1.82 (1H, ddd, J =
3.4, 5.8, 14.5 Hz), 19.3-2.02 (2H, m), 2.38 (1H,
m), 2.49 (1H, m), 2.58 (1H, diffused d, J = 4.5 Hz),
3.63 (1H, dd, J = 2.9, 10.3 Hz), 3.72 (1H, dd, J = 9.
2, 10.3 Hz), 4.07 (2H, diffused d, J = 5.7 Hz), 4.21
(1H, diffused d, J = 2.7 Hz), 5.37 (1H, diffused d,
J = 9.8 Hz), 5.55 (1H, ddd, J = 2.6,4.7, 9.7 Hz), 5.6
6 (1H, ddt, J = 1.3, 15.6, 6.3 Hz), 6.16 (1H, ddt, J
= 7.8,15.5, 1.3 Hz) IR (KBr) 3360, 3250, 2900, 1450, 1240, 1010, 970, 7
20 cm ^-1 analysis C ₁₅ H ₂₄ O ₃ : calculated value C, 71.39; H, 9.59. Measured value C,
71.05; H, 9.39. [Α] ²⁰ _D +175 ^o (c 0.81, MeOH)

Example 4

[0057]

[Chemical 15]

(1S, 2S, 4aR, 6S, 8S, 8aS) -1,2,4a, 5,6,7,8,8
a-Octahydro-1-ethoxycarbonyl-6- [2- (ethoxycarbonyl)-(E) -ethenyl] -8-hydroxy-2-methylnaphthalene (360 mg, 1.07 mmol) in tetrahydrofuran (6.
It was dissolved in 0 mL), a toluene solution of diisobutylaluminum hydride (1.00 mol / L, 5.5 mL, 5.5 mmol) was added under ice cooling, the temperature was raised to room temperature, and the mixture was stirred for 16 hours. Ethyl acetate (20 mL) and water (1.0 mL) were added to the reaction mixture under ice cooling to stop the reaction, and the insoluble material was filtered off. The residue obtained by concentrating the filtrate under reduced pressure was dissolved in methanol (7.0 mL), sodium borohydride (80 mg) was added, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure and the obtained residue was washed with ethyl acetate (20 m
It was dissolved in L) and washed with dilute hydrochloric acid (10 mL). The solid residue obtained by drying over magnesium sulfate and concentration under reduced pressure was crushed in a mixed solvent of toluene and hexane (1: 1) and collected by filtration (1S, 2S, 4aR, 6S, 8S, 8aS ) -1,2,4a, 5,6,7,8,8
a-Octahydro-8-hydroxy-1-hydroxymethyl-6-
[(E) -1- (3-Hydroxypropenyl)]-2-methylnaphthalene (176 mg, 65%) was obtained as colorless crystals. The various spectra of this product were completely in agreement with those obtained in Example 3.

Example 5

[0060]

[Chemical 16]

(1S, 2S, 4aR, 6S, 8S, 8aS) -1,2,4a, 5,6,7,8,8
a-Octahydro-8-hydroxy-1-hydroxymethyl-6-
[(E) -1- (3-hydroxypropenyl)]-2-methylnaphthalene (120 mg, 0.48 mmol) was dissolved in dichloromethane (2.0 mL), and pyridinium p-toluenesulfonate (8.0 mg,
0.03 mmol) and ethyl vinyl ether (151 mg, 2.1 mmol)
Were sequentially added under ice cooling. After stirring at room temperature for 16 hours, ethyl vinyl ether (75 mg, 1.0 mmol) and p-toluenesulfonic acid (8 mg, 0.04 mmol) were sequentially added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate (20 mL),
The extract was washed with saturated aqueous sodium hydrogen carbonate (20 mL) and dried over magnesium sulfate. The residue obtained by concentration under reduced pressure was dissolved in hexane (20 mL), activated carbon (500 mg) was added, and the mixture was stirred at room temperature for 1 hr.
The activated carbon was filtered off, and the filtrate was concentrated under reduced pressure (1S, 2
S, 4aR, 6S, 8S, 8aS) -1,2,4a, 5,6,7,8,8a-octahydro-8-
(1-ethoxyethoxy) -1- (1-ethoxyethoxy) methyl
-6-[(E) -1- (3- (1-ethoxyethoxy) propenyl)]-2-methylnaphthalene was quantitatively obtained as a pale yellow oily substance. This is based on three 1-ethoxyethoxy groups 8
Since it is a mixture of various diastereomers, the measurement of various spectra and the identification of the compound were carried out by the following Example 6, (1S, 2S, 4aR, 6S, 8S, 8aS) -1,2,4a, 5,6,7. It was carried out by derivatizing to 8,8,8a-octahydro-8-hydroxy-1-hydroxymethyl-6-[(E) -1-propenyl] -2-methylnaphthalene.

Reference Example 4

[0063]

[Chemical 17]

Liquid ammonia (10 mL) was added to metallic lithium (40 mL).
mg, 5.7 mmol) was added at -33 ° C (boiling point of liquid ammonia), and the reaction solution turned deep blue at the same temperature (1S, 2S, 4aR, 6S,
8S, 8aS) -1,2,4a, 5,6,7,8,8a-octahydro-8- (1-ethoxyethoxy) -1- (1-ethoxyethoxy) methyl-6-[(E) -1
A solution of 8- (3- (1-ethoxyethoxy) propenyl)]-2-methylnaphthalene in diastereomer mixture based on three 1-ethoxyethoxy groups in tetrahydrofuran (0.4
76 mmol, 5.0 mL) was added. After stirring at -33 ° C for 3 hours, solid ammonium chloride (500 mg, 9.3 mmol) and methanol (1.0 mL) were sequentially added to stop the reaction, and ammonia was removed by evaporation under normal pressure. The residue was diluted with ethyl acetate (20 mL), washed with water (10 mL), and dried over magnesium sulfate. The residue obtained by concentration under reduced pressure was dissolved in methanol (5.0 mL) and p-toluenesulfonic acid (2.0 mg, 0.01 mmol) was added.
Was added and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure to 1/4 volume, diluted with ethyl acetate (20 mL), washed with saturated aqueous sodium hydrogen carbonate (20 mL), and dried over magnesium sulfate. The residue obtained by concentration under reduced pressure was purified by column chromatography (hexane: ethyl acetate = 3: 1) to obtain (1S, 2S, 4aR, 6S, 8S, 8aS) -1,2,4a, 5,6. , 7,8,8a-Octahydro-8-hydroxy-1-hydroxymethyl-6-[(E) -1-
Propenyl] -2-methylnaphthalene (91 mg, 81%) was obtained as a colorless oily substance.

¹ H NMR (CDCl ₃ -D ₂ O, 400 MHz) δ 0.82
(3H, d, J = 7.0 Hz), 1.22 (1H, dt, J = 2.4, 10.7 Hz),
1.33 (3H, dt, J = 4.9, 13.1 Hz), 1.68 (3H, dt, J = 6.
4, 1.4 Hz), 1.76-1.83 (2H, m), 1.96-2.04 (2H, m),
2.36-2.49 (2H, m), 2.53 (1H, m), 3.61 (1H, dd, J =
3.1, 10.4 Hz), 3.75 (1H, dd, J = 8.8, 10.4 Hz), 4.19
(1H, diffused q, J = 2.8 Hz), 5.39 (1H, diffused d,
J = 9.8 Hz), 5.48-5.58 (2H, m), 5.92 (1H, ddq, J = 7.
0, 15.4, 1.6 Hz) IR (neat) 3340, 2900, 1440, 1000, 720 cm ^-1 MS (CI, low resolution) 237 (M ⁺ +1), 219, 201, 187 [α] ²⁰ _D +144 ^o (c 1.52, CHCl ₃ )

Reference Example 5

[0067]

[Chemical 18]

(1S, 2S, 4aR, 6S, 8S, 8aS) -1,2,4a, 5,6,7,8,8
a-Octahydro-8-hydroxy-1-hydroxymethyl-2-
Methyl-6-((E) -1-propenyl) naphthalene (260 mg, 1.1
mmol) was dissolved in dimethylformamide (5.0 mL), imidazole (150 mg, 2.2 mmol) and t-butyldimethylsilyl chloride (199 mg, 1.3 mmol) were sequentially added thereto, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with ligroin (30 mL) and washed twice with saturated brine (20 mL). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure, and the resulting residue was subjected to column chromatography (hexane: ethyl acetate = 3
(1S, 2S, 4aR, 6S, 8S, 8aS) -1,
2,4a, 5,6,7,8,8a-Octahydro-1- (t-butyldimethylsiloxymethyl) -8-hydroxy-2-methyl-6-((E) -1-propenyl) naphthalene (384 mg , 100%) was obtained as a colorless oily substance. Various spectra of this product can be obtained by known methods (CMB
lackwell, et al., J. Org. Chem., 57, 5596 (1992))
Which was exactly the same as that obtained by.

Reference Example 6

[0070]

[Chemical 19]

(1S, 2S, 4aR, 6S, 8S, 8aS) -1,2,4a, 5,6,7,8,8
a-Octahydro-1- (t-butyldimethylsiloxymethyl)-
8-Hydroxy-2-methyl-6-((E) -1-propenyl) naphthalene (371 mg, 1.1 mmol) was dissolved in pyridine (7.0 mL) to give 2,
2-Dimethylbutyryl chloride (484 mg, 3.6 mmol) and 4-dimethylaminopyridine (14.6 mg, 0.12 mmol) were added, and 90
Stirred for 16 hours at ℃. The reaction mixture was ethyl acetate (80 mL)
It was diluted with and was washed successively with 3 N hydrochloric acid (80 mL), saturated saline (50 mL), saturated aqueous sodium hydrogen carbonate (50 mL), and saturated saline (50 mL). The organic layer was dried over magnesium sulfate, concentrated under reduced pressure, and the obtained residue was suspended in acetonitrile (5.0 mL). A solution of hydrogen fluoride in acetonitrile (2%, 15 mL) was added, and the mixture was stirred at room temperature for 2 hours.
Stir for hours. The residue obtained by concentrating the reaction mixture under reduced pressure was dissolved in ethyl acetate (50 mL), and washed successively with saturated aqueous sodium hydrogen carbonate (50 mL) and saturated brine (50 mL). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure, and the resulting residue was purified by column chromatography (hexane: ethyl acetate = 7: 1) (1S, 3S, 4aR, 7S, 8S, 8aS) -1. , 2,3,4,4a, 7,8,8
a-Octahydro-8- (hydroxymethyl) -7-methyl-3-
[(E) -1-Propenyl] -1-naphthalenyl 2,2-dimethylbutyrate (299 mg, 84%) was obtained as colorless crystals.

Mp. 103-105 ° C. (hexane) ¹ H NMR (CDCl ₃ , 200 MHz) δ 0.86 (3H, t, J = 7.5 H
z), 0.94 (3H, d, J = 7.0 Hz), 1.17 (3H, s), 1.18 (3
H, s), 1.12-1.42 (3H, m), 1.60 (2H, q, J = 7.4Hz),
1.57-1.63 (3H, m), 1.68-1.82 (2H, m), 1.89-2.04
(m, 2H), 2.44-2.60 (3H, m), 3.50 (1H, dt, J = 5.2, 9.
7 Hz), 3.65 (1H, dt, J = 4.6, 10.4 Hz), 5.05 (1H, q,
J = 2.7 Hz), 5.30-5.47 (2H, m), 5.66 (1H, ddd, J = 2.
4, 4.9, 9.7Hz), 5.78 (1H, ddq, J = 8.1, 15.3, 1.6 H
z) IR (KBr) 3420, 2900, 1710, 1240, 1150 cm ^-1 Analysis C ₂₁ H ₃₄ O ₃ : Calculated value C, 75.41; H, 10.25. Measured value
C, 75.57; H, 10.27. [Α] ²⁰ _D +172 ^o (c 0.54, CHCl ₃ ) The above spectrum has known values (CM Blackwell, et al., J.
Org. Chem., 57, 5596 (1992)).

[Procedure amendment]

[Submission date] March 18, 1994

[Procedure Amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0061

[Correction method] Change

[Correction content]

(1S, 2S, 4aR, 6S, 8S, 8aS) -1,2,4a, 5,6,7,8,8
a-Octahydro-8-hydroxy-1-hydroxymethyl-6-
[(E) -1- (3-hydroxypropenyl)]-2-methylnaphthalene (120 mg, 0.48 mmol) was dissolved in dichloromethane (2.0 mL), and pyridinium p-toluenesulfonate (8.0 mg,
0.03 mmol) and ethyl vinyl ether (151 mg, 2.1 mmol)
The was example sequentially wise under ice cooling. After stirring at room temperature for 16 hours, ethyl vinyl ether (75 mg, 1.0 mmol) and p-toluenesulfonic acid (8 mg, 0.04 mmol) were sequentially added, and the mixture was stirred at room temperature for 2 hours.
Stir for hours. The reaction mixture was diluted with ethyl acetate (20 mL), washed with saturated aqueous sodium hydrogen carbonate (20 mL), and dried over magnesium sulfate. The residue obtained by concentration under reduced pressure was dissolved in hexane (20 mL), activated carbon (500 mg) was added, and the mixture was stirred at room temperature for 1 hr. The activated carbon was filtered off, and the filtrate was concentrated under reduced pressure (1
S, 2S, 4aR, 6S, 8S, 8aS) -1,2,4a, 5,6,7,8,8a-octahydro
-8- (1-ethoxyethoxy) -1- (1-ethoxyethoxy) methyl-6-[(E) -1- (3- (1-ethoxyethoxy) propenyl)]-
2-Methylnaphthalene was quantitatively obtained as a pale yellow oily substance. Since this is a mixture of eight diastereomers based on three 1-ethoxyethoxy groups, the measurement of various spectra and the identification of the compound were carried out by the following Example 6 ((1S, 2S, 4aR, 6S, 8S, 8aS ) -1,2,4a, 5,6,7,8,8a-Octahydro-8-hydroxy-1-hydroxymethyl-6-[(E) -1-propenyl] -2-methylnaphthalene went.

Claims (1)

[Claims] 1. The following general formula: [In the formula, R ¹ is an oxycarbonyl group represented by COOR ⁴ (R ⁴ is a hydrogen atom, a linear or branched lower alkyl group having 1 to 5 carbon atoms, a substituted or unsubstituted aralkyl group, or A substituted or unsubstituted aryl group) or an oxymethyl group represented by CH ₂ OR ⁵ (R ⁵ represents a hydrogen atom or a hydroxyl protecting group), and R ² represents a hydrogen atom or a hydroxyl protecting group. Where R ³ is an oxycarbonyl group represented by COOR ⁶ (R ⁶ is a hydrogen atom, carbon number 1
~ 5 represents a linear or branched lower alkyl group, a substituted or unsubstituted aralkyl group, or a substituted or unsubstituted aryl group) or an oxymethyl group represented by CH ₂ OR ⁷ (R ⁷ is Represents a hydrogen atom or a hydroxyl-protecting group]] (2S, 4aR, 6S, 8
S, 8aS) -1,2,4a, 5,6,7,8,8a-
Octahydro-2-methyl-6-substituted alkenylnaphthalene derivative.