JP3169425B2 - Azidopentane cyclitol - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[Object of the invention]

[0002]

The compound (I) of the present invention has a strong α
Formula (XVI) which is useful as an antiobesity agent or an antidiabetic agent because it has glucosidase inhibitory activity

[0003]

Embedded image

The present invention relates to a synthetic intermediate of aminopentane cyclitol represented by the formula:

[0005]

2. Description of the Prior Art Aminopentane cyclitol has been obtained by hydrolyzing trehazolin isolated from a culture of Micromonospora actinomycetes as an inhibitor of trehalase known as the molting hormone of silkworm. (Journal of Antibiotics, Vol. 44, p. 1165, 1991 (J. An-tibi
otics, 1165 (1991)). It is also obtained by hydrolyzing the aglycone of trehazolin isolated from the culture solution of actinomycetes of the genus Micromonospora and actinomycetes of the genus Amycolatopsis (Japanese Patent Application No. 3-213450). However, no report has been made on synthetic aminopentanecyclitol and its synthetic intermediate.

[0006]

The object of the present invention is to obtain aminopentane cyclitol or a derivative thereof,
The use of aminopentane cyclitol obtained by fermentation as a starting material results in low production and the synthesis of various derivatives is not possible. An object of the present invention is to obtain an intermediate for obtaining aminopentane cyclitol or a derivative thereof in a small number of steps and in a large amount in a high yield.

[0007]

Configuration of the Invention

[0008]

Means for Solving the Problems In order to solve the above-mentioned problems, the present inventors have conducted intensive studies. As a result, by using a known substance as a starting material, the present invention can be performed easily, in a small number of steps, and with high efficiency. It has been found that an intermediate which can be derived in a yield to aminopentanecyclitol or a derivative thereof can be synthesized.

The intermediate of the present invention has the general formula

[0010]

Embedded image

Has the following. In the above formula, R ¹ and R ² are the same or different and are a C ₁ -C ₄ alkoxymethyl group, a C _1-
C ₄ alkoxy C ₁ -C ₄ alkoxymethyl group or C
₇ -C ₁₁ aralkyl oxymethyl group, R ³ is C ₇
—C _{11 represents an} aralkyl group. In the above, R ¹ and R
The C ₁ -C ₄ alkoxymethyl group in the definition of ² is, for example, a straight-chain or branched-chain alkoxymethyl group having 1 to 4 carbon atoms such as methoxymethyl, ethoxymethyl, isopropoxymethyl, propoxymethyl and butoxymethyl. And is preferably a methoxymethyl group.

In the above, the C ₁ -C ₄ alkoxy C ₁ -C ₄ alkyleneoxymethyl group in the definition of R ¹ and R ² is methoxymethoxymethyl, methoxyethoxymethyl, ethoxymethoxymethyl, ethoxyethoxymethyl, ethoxymethoxyethyl. A straight-chain or branched chain having 1 to 4 carbon atoms, which is substituted by a straight-chain or branched-chain alkoxy group having 1 to 4 carbon atoms, such as isopropoxymethoxymethyl, isopropoxyethoxymethyl, butoxymethoxymethyl; It may be an alkyleneoxymethyl group, preferably a methoxyethoxymethyl group.

In the above, the C ₇ -C ₁₁ aralkyloxymethyl group in the definition of R ¹ and R ² is a group having 7 to 11 carbon atoms such as benzyloxymethyl, 4-methoxybenzyloxymethyl and naphthyl 1-methyloxymethyl.
Aralkyloxymethyl groups, preferably a benzyloxymethyl group.

In the above, C _7- in the definition of R ³
The C ₁₁ aralkyl group has a carbon number such as benzyl, 4-methoxybenzyl, 3,4-dimethoxybenzyl, 4-ethoxybenzyl, 4-methylbenzyl, 4-ethylbenzyl, naphthyl-1-methyl, and naphthyl-2methyl. 1
It may be a benzyl group or a naphthyl group which may be substituted with 1 to 2 alkyl groups or an alkoxy group having 1 to 2 carbon atoms, and is preferably a benzyl or 4-methoxybenzyl group. As preferred compounds in the above general formula (I), (1) a compound in which R ¹ is a methoxymethyl group, a methoxyethoxymethyl group or a benzyloxymethyl group, (2) R ² is a methoxymethyl group, a methoxyethoxymethyl group or A compound in which R ³ is a benzyl group, a compound in which R ³ is a 4-methoxybenzyl group, and (1) a compound in which R ¹ is a methoxymethyl group; )
Compounds wherein R ² is a methoxymethyl group, (3) R ³
Is a benzyl group.
Table 1 specifically exemplifies the compounds in the general formula (I).

[0015]

[Table 1]

[0016]

Embedded image

─────────────────────────────────── Substituent (coordination) No. (1 position) R ³ (2nd) R ² (3rd) R ¹ (4th) (5th) ──────────────────────────── ─────── 1 (1R, 1 α) Bz (2β) MOM (3 α) MOM (4β) (5β) 2 (1R, 1 α) 4-MeO-Bz (2β) MOM (3 α) MOM (4β) (5β) 3 (1R, 1 α) Bz (2β) MEM (3 α) MEM (4β) (5β) 4 (1R, 1 α) Bz (2β) BOM (3 α) BOM (4β) (5β) 5 (1S, 1 β) Bz (2β) MOM (3 α) MOM (4β) (5α) 6 (1S, 1 β) 4-MeO-Bz (2β) MOM (3 α) MOM (4β) (5α) 7 (1S, 1 β) Bz (2β) MEM (3 α) MEM (4β) (5α) 8 (1S, 1 β) Bz (2β) BOM (3 α) BOM (4β) (5α) 9 (1R, 1 α) Bz (2α) MOM (3 α) MOM (4β) (5β) 10 (1R, 1 α) 4-MeO-Bz (2α) MOM (3 α) MOM (4β) (5β) 11 (1R, 1 α) Bz (2α) MEM (3 α) MEM (4β) (5β) 12 (1S, 1 β) Bz (2α) MOM (3 α) MOM (4β) (5α) 13 (1S, 1 β) 4-MeO-Bz (2α) MOM (3 α) MOM (4β) (5α) 14 (1S, 1 β) Bz (2α) MEM (3 α) MEM (4β) (5α) ───── ───────────────────────────── In Table, abbreviations indicate the following groups or sign.

[0018] Bz ········ benzyl BOM ········ benzyloxymethyl MeO ········ methoxy MOM ········ methoxymethyl MEM · · · ···· methoxyethoxymethyl The compound (I) of the present invention can be easily synthesized by the method described below.

[0019]

Embedded image

[0020]

Embedded image

[0021]

Embedded image

[0022]

Embedded image

In the above formula, R ¹ , R ² , R ³ , R ⁴ and R
⁵ has the same meaning as described above.

I _a , I _b , I _c , I _d are the same as I.

In the above, C _2- in the definition of R ⁴
The C ₅ aliphatic alkanoyl group may be, for example, a linear or branched alkanoyl group having 2 to 5 carbon atoms such as acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, and pivaloyl. , An acetyl group.

In the above, C _6- in the definition of R ⁴
C ₁₁ aromatic alkanoyl groups include, for example, benzoyl, 4
-It may be an aromatic alkanoyl group having 6 to 11 carbon atoms such as methoxybenzoyl or naphthylcarboxyl group, and is preferably a benzoyl group.

In the above, di C ₁ in the definition of R ⁵
-C ₄ alkylmono C ₆ -C ₁₀ arylsilyl group C ₁
-C ₄ alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec- butyl,
ter - be straight-chain or branched alkyl group having 1 to 4 carbon, such as butyl, preferably, ter - butyl, C ₆ -C ₁₀ aryl silyl group phenyl, tolyl, It may be an aromatic hydrocarbon group having 6 to 10 carbon atoms such as naphthyl, and is preferably a phenyl group. In the above, the tri-C ₁ -C ₄ alkylsilyl group in the definition of R ⁵ is, for example, trimethylsilyl, triethylsilyl, tripropylsilyl, dimethylisopropylsilyl, dimethylbutylsilyl, dimethylisobutylsilyl, dimethylsec-butylsilyl, dimethylter- It may be a linear or branched trialkylsilyl group having 1 to 4 carbon atoms such as butylsilyl, and is preferably a trimethylsilyl or dimethyl ter-butylsilyl group.

In the above, the halogen atom in the definition of X represents, for example, chlorine, bromine or iodine. Preferably, it is chlorine.

The first step is a step of producing a compound having the general formula (III), which is achieved by reacting an oximation agent with a compound having the general formula (II) in an inert solvent in the presence of a base. Is done.

Compound (II) can be prepared, for example, from B.I. Burnett, A. Bazera, Helvetica Kimika Acta, Vol. 62, p. 1990, 1979 (B. Berne
t, A, Ba-sella: HELVETICA CHIMICA ACTA, 62 , (1979)).

The inert solvent used is, for example, ethers such as diethyl ether, dioxane, tetrahydrofuran, methylene chloride, chloroform, carbon tetrachloride,
It can be a mixed solvent with halogenated hydrocarbons such as dichloroethane, aromatic hydrocarbons such as benzene and toluene, aliphatic hydrocarbons such as n-pentane, n-hexane and n-octane, and water. Preferably, they are hydrated ethers (particularly, water-diethyl ether).

The oximation agent used is, for example, a hydroxyamine mineral salt such as hydroxyamine hydrochloride, hydroxyamine bromate, hydroxyamine sulfate, and preferably hydroxyamine hydrochloride.

The base used is, for example, an alkali metal bicarbonate such as sodium bicarbonate or potassium bicarbonate, an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide, calcium hydroxide, magnesium hydroxide. Alkaline earth metal hydroxides such as sodium carbonate, potassium carbonate such as potassium carbonate, alkali metal acetates such as sodium acetate, alkali metal fluorides such as sodium fluoride and potassium fluoride,
Tertiary lower alkylamines such as triethylamine, ethyldiisopropylamine, tributylamine, 1,8-
Diazabicyclo [5.4.0] undecane-7-ene (DB
U), 1,4-diazabicyclo [2.2.2] octane (DA
It can be a tertiary cycloaliphatic amine such as BCO), preferably an alkali metal carbonate, especially sodium carbonate.

The reaction temperature and the reaction time vary depending on the type of the solvent and the type of the base.
° C (preferably 15 ° C to 25 ° C), and the reaction time is usually 15 minutes to 24 hours (preferably 5 hours to 15 hours).

After completion of the reaction, the target compound of this reaction is collected from the reaction mixture according to a conventional method. For example, water is added to the reaction mixture, or the reaction mixture from which insolubles have been removed is washed with an alkali such as sodium carbonate or sodium hydroxide, and then extracted with a water-immiscible organic solvent such as ethyl acetate. After drying with magnesium or the like, it can be obtained by distilling off the solvent. If necessary, recrystallization,
It can be purified by column chromatography or the like.

The second step is a step for preparing a compound having the general formula (IV), which comprises treating an oxime having the general formula (III) with an oxidizing agent in an inert solvent in the presence of a base catalyst. This is achieved by generating nitrile oxide and causing a 2 + 3 cycloaddition reaction to a double bond in the molecule.

The inert solvent used can be, for example, halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, preferably methylene chloride.

The oxidizing agent used is, for example, sodium hypochlorides such as sodium hypochloride and sodium hypobromide, and preferably sodium hypochloride.

The base catalyst used is, for example, a tertiary lower alkylamine such as triethylamine, ethyldiisopropylamine, tributylamine, 1,8-diazabicyclo [5.4.0] undecane-7-ene (DBU), Four
Tertiary alicyclic amines such as diazabicyclo [2.2.2] octane (DABCO), preferably tertiary lower alkylamines, especially triethylamine.

The reaction temperature and reaction time depend on the starting compound,
The reaction temperature is usually −10 ° C. to 50 ° C. (preferably 0 ° C. to 10 ° C.), and the reaction time is usually 5 minutes to 24 hours (preferably 3 minutes), depending on the type of solvent and base.
0 minutes to 5 hours).

After completion of the reaction, the target compound of this reaction is collected from the reaction mixture according to a conventional method. For example, it can be obtained by adding water to the reaction mixture, extracting with a water-immiscible organic solvent such as methylene chloride, drying over anhydrous magnesium sulfate or the like, and then distilling off the solvent. if needed,
It can be further purified by a conventional method, for example, column chromatography.

The third step is a step for producing a compound having the general formula (V). The imine is obtained by subjecting the compound having the general formula (IV) to a hydrogenolysis reaction in an inert solvent in the presence of a base catalyst. And performing a hydrolysis reaction of the imine in the presence of an acid catalyst.

The inert solvent used is, for example, alcohols such as methanol and ethanol, ethers such as diethyl ether, dioxane and tetrahydrofuran, and halogenated compounds such as methylene chloride, chloroform, carbon tetrachloride and dichloroethane. Hydrocarbons, benzene, aromatic hydrocarbons such as toluene, n-pentane, n-
It may be an aliphatic hydrocarbon such as hexane or n-octane, or a mixed solvent of the above solvent and water, and is preferably methanol-water-dioxane.

The catalyst used in the hydrogenolysis reaction is Raney.
Transition metals such as nickel and palladium-carbon, preferably Raney-nickel.

The hydrogen pressure used in the hydrogenolysis reaction is usually 0.5 to 3 atm (preferably 1 atm).

The catalyst used in the hydrolysis reaction may be a mineral acid such as hydrochloric acid, sulfuric acid, boric acid, or an organic acid such as p-toluenesulfonic acid, camphorsulfonic acid, preferably a mineral acid (particularly, Boric acid).

The reaction temperature and reaction time depend on the starting compound,
The reaction temperature is usually 0 ° C. to 100 ° C. (preferably 10 ° C.) at the stage of obtaining the imine, although it depends on the type of the solvent and the type of the catalyst.
C. to 50 ° C.), and the reaction time is 10 minutes to 24 hours (preferably 30 minutes to 5 hours). In the stage of hydrolysis of the imine, the reaction temperature is usually 0 ° C. to 100 ° C. (preferably Is 10 ° C. to 50 ° C.), and the reaction time is usually 5 minutes to 24 hours (preferably 1 hour to 24 hours).

In this reaction, the reaction for obtaining an imine and the hydrolysis reaction can be carried out simultaneously, and the target compound can be obtained by mixing Raney-nickel and boric acid. After completion of the reaction, the target compound of this reaction is collected from the reaction mixture according to a conventional method. For example, it can be obtained by filtering the reaction mixture, concentrating, extracting with a water-immiscible organic solvent such as methylene chloride, drying over anhydrous magnesium sulfate or the like, and then distilling off the solvent. if needed,
It can be further purified by a conventional method, for example, recrystallization, column chromatography and the like.

The fourth step is a step of producing a compound having the general formula (VII), in an inert solvent in the presence of a base.
This is achieved by reacting a compound having the general formula (V) with a protecting agent having the general formula (VI).

The inert solvent used is, for example, ethers such as tetrahydrofuran, dioxane, diethyl ether, dimethoxyethane, methylene chloride, chloroform, carbon tetrachloride, halogenated hydrocarbons such as dichloroethane, benzene, Aromatic hydrocarbons such as toluene, acetates such as ethyl acetate and methyl acetate, amides such as N, N-dimethylacetamide, N, N-dimethylformamide, N-methyl-2-pyrrolidinone, and acetonitrile And preferably amides (especially N, N-dimethylformamide). Bases used are, for example, sodium carbonate, alkali metal carbonates such as potassium carbonate, sodium bicarbonate, alkali metal bicarbonates such as potassium bicarbonate, sodium hydroxide, potassium hydroxide,
Alkali metal hydroxides such as lithium hydroxide, tertiary lower alkylamines such as triethylamine, ethyldiisopropylamine and tributylamine; 1,8-diazabicyclo [5.4.0] undecane-7-ene (DBU);
, 4-diazabicyclo [2.2.2] octane (DABC
Tertiary alicyclic amines such as O), imidazole, diethylaniline, dimethylaniline, 4-dimethylaminopyridine, pyridine, and preferably tertiary lower alkylamines or tertiary alicyclic amines (especially , Imidazole)
It is.

The protecting agent used is, for example, tri C ₁ -C ₄ alkylsilyl halide such as trimethylsilyl chloride, triethylsilyl chloride, triisobutylsilyl chloride, dimethyl ter-butylsilyl chloride, diphenyl ter-butylsilyl chloride. , C ₁ -C ₄
Be a alkyl di C ₆ -C ₁₀ aryl silyl halide, preferably a trialkylsilyl halide (especially,
Dimethyl ter-butylsilyl chloride).

The reaction temperature and reaction time depend on the starting compound,
Although it depends on the type of solvent and base, it is usually 0 ° C to 80 ° C.
° C (preferably 0 ° C to 30 ° C), usually 15 minutes to 24 hours (preferably 1 hour to 8 hours).

After completion of the reaction, the target compound of this reaction is collected from the reaction mixture according to a conventional method. For example, it can be obtained by extracting the reaction mixture with a water-immiscible organic solvent such as diethyl ether or ethyl acetate, drying over anhydrous magnesium sulfate or the like, and distilling off the solvent. If necessary, it can be further purified by a conventional method, for example, recrystallization, column chromatography and the like.

The fifth step is a step of preparing compounds having the general formulas (VIIIβ) and (VIIIα), and treating the compound having the general formula (VII) with a reducing agent in an inert solvent in the presence of an additive. Is achieved by doing

The inert solvent used is, for example, ethers such as tetrahydrofuran, dioxane and diethyl ether, alcohols such as methanol, ethanol and t-butanol, and a mixed solvent of water and the above organic solvent. It is preferably a hydrous alcohol (particularly water-ethanol).

The reducing agent used can be, for example, alkali metal boron hydrides such as sodium boron hydride, sodium boron cyanohydride, aluminum hydrides such as lithium aluminum hydride and diisobutyl aluminum hydride; Preferably, they are alkali metal boron hydrides (particularly sodium boron hydride).

This reaction is preferably carried out by adding cerium chloride (CeCl _3.
7H ₂ O). The reaction temperature and reaction time vary depending on the types of the starting compound, the solvent, the reducing agent and the target compound, but the reaction temperature is usually -78 ° C to 50 (preferably 0 ° C to 40 ° C), and the reaction time is
It is usually 15 minutes to 24 hours (preferably 30 minutes to 2 hours).

In this reaction, a mixture of compounds (VIII) and (VIII) is obtained, and each compound is easily separated by a conventional method, for example, silica gel column chromatography.

The sixth step is a step of producing a compound having the formula (X), wherein the compound of the formula (VI) is prepared in an inert solvent in the presence of a base.
(IIβ) is reacted with a protecting agent represented by the general formula (IX).

The protecting agents used are benzyl chloride,
Benzyl bromide, 4-methoxybenzyl chloride,
It may be a benzyl halide such as 3,4-dimethoxybenzyl chloride, and is preferably benzyl bromide.

The inert solvent used is, for example, ethers such as tetrahydrofuran, dioxane, diethyl ether, diglyme, dimethoxyethane, halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride and dichloroethane; N, N-dimethylacetamide, N, N-dimethylformamide, N-methyl-2
Amides such as pyrrolidinone, nitriles such as acetonitrile, sulfoxides such as dimethylsulfoxide, and preferably ethers and amides (particularly dimethylformamide).

The base used is, for example, an alkali metal hydride such as sodium hydride, potassium hydride or lithium hydride; an alkali metal alkoxide such as sodium methoxide, sodium ethoxide or potassium t-butoxide; Amides, alkali metal amides such as lithium isopropylamide, tertiary lower alkylamines such as triethylamine, ethyldiisopropylamine, tributylamine, 1,8-diazabicyclo [5.4.0] undecane-7-ene (DBU), 1, 4−
It can be a tertiary cycloaliphatic amine such as diazabicyclo [2.2.2] octane (DABCO), preferably an alkali metal hydride, especially sodium hydride.

The reaction temperature and reaction time depend on the starting compound,
Depending on the type of solvent and base, the reaction temperature is usually 0.
C. to 100 C. (preferably 10 C. to 30 C.)
The reaction time is generally 5 minutes to 24 hours (preferably 1 hour to 5 hours).

After completion of the reaction, the target compound of this reaction is collected from the reaction mixture according to a conventional method. For example, if an excess of alkali metal hydride remains in the reaction mixture, water or alcohols are added to decompose the mixture, and then water is added to the reaction mixture to form a water-immiscible organic compound such as diethyl ether or ethyl acetate. It can be obtained by extracting with a solvent, drying over anhydrous magnesium sulfate or the like, and then distilling off the solvent.
If necessary, it can be further purified by a conventional method, for example, column chromatography or the like.

The seventh step is a step for producing a compound having the general formula (XI), which is achieved by reacting a compound having the general formula (X) with a silyl group-cleaving agent to remove a protecting group.

The silyl group-cleaving agent used may preferably be a dilute mineral acid such as dilute hydrochloric acid or dilute sulfuric acid, or an ammonium fluoride such as tetrabutylammonium fluoride. Butyl ammonium fluoride. The inert solvent used is
For example, tetrahydrofuran, dioxane, ether,
Ethers such as dimethoxyethane, methylene chloride,
It can be a halogenated hydrocarbon such as chloroform, carbon tetrachloride, dichloroethane, or an aromatic hydrocarbon such as benzene, toluene, or xylene, and is preferably an ether (particularly, tetrahydrofuran). The reaction temperature is usually from 0 ° C to 80 ° C (preferably from 10 ° C to 40 ° C).
° C), and the reaction time is usually 10 minutes to 24 hours (preferably 30 minutes to 5 hours).

After completion of the reaction, the target compound of this reaction is collected from the reaction mixture according to a conventional method. For example, it can be obtained by adding water to the reaction mixture, extracting with a water-immiscible organic solvent such as ethyl acetate, washing with a saturated saline solution, drying with anhydrous magnesium sulfate or the like, and distilling off the solvent. it can. If necessary, it can be further purified by a conventional method, for example, column chromatography or the like.

The eighth step is a step for producing a compound having the general formula (XIIα) and a compound having the general formula (XIIβ). The compound having the general formula (XI) is prepared in an inert solvent in the presence of a catalyst or It is achieved by reacting with an oxidizing agent in the absence (preferably in the presence of a catalyst).

Examples of the oxidizing agent used include peracetic acid, perphthalic acid, perbenzoic acid, m-chloroperbenzoic acid,
Organic peracids, such as ter-butyl hydroperoxide, can be hydrogen peroxide, preferably organic peracids (especially,
ter-butyl hydroperoxide).

Examples of the catalyst used include complexes of vanadium such as vanadium acetylacetonate, titanium tetraisopropoxide, titanium, molybdenum, cobalt, etc., (L) -diethyl tartrate, and (L) -diisopropyl tartrate. Optically active organic acid esters such as
More than one species is used in combination with the oxidizing agent. Suitable catalyst and oxidizing agent combinations are, for example, tetraisopropyl orthotitanate- (L) -diisopropyl tartrate-ter-butyl hydroperoxide or tetraisopropyl orthotitanate- (D) -diisopropyl tartrate-ter-
Compound (XIIα) is selectively obtained by using the former, and (XIIβ) is selectively obtained by using the latter.

Examples of the solvent used include halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride and dichloroethane, aromatic hydrocarbons such as benzene and toluene, n-pentane and n-hexane. Kisane,
It may be an aliphatic hydrocarbon such as cyclopentane or cyclohexane, or an acetate such as methyl acetate, ethyl acetate or butyl acetate, preferably a halogenated hydrocarbon (especially methylene chloride). is there.

The reaction temperature of this reaction is usually -78 ° C to 100 ° C (preferably -40 ° C to 30 ° C), and the reaction time is usually 15 minutes to 24 hours (preferably 1 hour to 10 hours). Time).

After completion of the reaction, the target compound of this reaction is collected from the reaction mixture according to a conventional method. For example, a 10% aqueous sodium hydroxide solution is added to the reaction mixture, extracted with a water-immiscible organic solvent such as diethyl ether, washed with saturated saline, dried over anhydrous magnesium sulfate, and the like, and then the solvent is distilled off. Can be obtained by if needed,
It can be further purified by a conventional method, for example, column chromatography.

[0074] In the ninth step, by the formula to produce a compound having a (I _a), a compound inert solvent having the general formula (XIIα), the presence of an acid catalyst, by treatment with an azide agent Achieved.

The azidating agent used includes, for example,
It can be an azide such as sodium azide, trimethylsilyl azide, diphenylphosphoryl azide, and is preferably sodium azide.

The acid catalyst used can be, for example, anhydrous ammonium chloride, a Lewis acid such as boron trifluoride, preferably anhydrous ammonium chloride.

The inert solvents used are, for example, ethers such as diethyl ether, dioxane, tetrahydrofuran, methylene chloride, chloroform, carbon tetrachloride,
Halogenated hydrocarbons such as dichloroethane, benzene, aromatic hydrocarbons such as toluene, methyl acetate,
Acetates such as ethyl acetate and butyl acetate, lower fatty acids such as formic acid and acetic acid, N, N-dimethylacetamide, N, N-dimethylformamide, N-methyl-
An amide such as 2-pyrrolidinone, a sulfoxide such as dimethylsulfoxy, a nitrile such as acetonitrile, and a mixed solvent with water, preferably an amide (particularly N, N-dimethylformamide) ).

The reaction temperature is usually 0 ° C. to 150 ° C. (preferably 80 ° C. to 150 ° C.), and the reaction time is usually 1
Time to 7 days (preferably 1 day to 3 days).

After completion of the reaction, the target compound of this reaction is collected from the reaction mixture according to a conventional method. For example, water is added to the reaction mixture, extracted with a water-immiscible organic solvent such as methylene chloride or ethyl acetate, washed with saturated saline, dried over anhydrous magnesium sulfate, and the like, and the solvent is distilled off. Can be. If necessary, it can be further purified by a conventional method, for example, column chromatography or the like.

By subjecting the compound having the general formula (XIIβ) to the same treatment, a compound having the general formula (I _b ) is produced.

The tenth step is a step for producing a compound having the formula (XIII), which is carried out in an inert solvent in the presence of a base.
This is achieved by reacting a compound having the formula (VIIIα) with a protecting agent represented by the general formula (IX).

This step is performed in the same manner as in the sixth step. The eleventh step is a step of producing a compound having the general formula (XIV), which is achieved by reacting a compound having the general formula (XIII) with a silyl group-cleaving agent. This step is performed in the same manner as in the seventh step.

The twelfth step is a step for producing a compound having a compound having the general formula (XVα) and the compound having the general formula (XVβ). The compound having the general formula (XV) is oxidized alone or in a catalyst in an inert solvent. It is achieved by processing in the presence.

This step is performed in the same manner as in the eighth step. The thirteenth step is a step of producing a compound having the formula (I _c ), which is achieved by treating the compound having the formula (XVα) with an azidating agent in an inert solvent in the presence of a catalyst.

This step is performed in the same manner as in the ninth step.

By subjecting a compound having the general formula (XVβ) to a similar treatment, a compound having the general formula (I _d ) is produced.

[0087]

According to the present invention, aminopentane cyclitol and its derivatives useful as anti-obesity drugs or anti-diabetic drugs are synthesized by using a readily available known compound as a starting material and utilizing a known reaction. To provide a short-step and easy synthesis method of azidopentane cyclitol, which is an intermediate for the above.

The compound (I) of the present invention can easily lead to a useful aminopentane cyclitol (XVI). As shown below, shows the steps leading to the amino pentane Sai chestnut Torr corresponding to (I _a) as the starting material (XVI _a).

[0089]

Embedded image

[0090]

Embedded image

[0091]

Embedded image

In the above formula, R ⁶ , R ⁷ and R ⁸ are the same or different and each represents a C ₂ -C ₅ lower aliphatic alkanoyl group or a C ₇ -C ₁₁ aromatic alkanoyl group which may be substituted with halogen. .

The fourteenth step is a step for producing a compound having the general formula (XVII), wherein the compound having the general formula (I) is treated with a reducing agent in an inert solvent, or
This is achieved by catalytic reduction.

The reducing agent used can be, for example, trimethylphosphine, sodium triethylphosphine, trialkylphosphine, trialkylphosphine such as triphenylphosphine, triarylphosphine such as triphenylphosphine, and preferably triphenylphosphine. Phosphine.

The inert solvent used includes, for example, ethers such as tetrahydrofuran, dioxane and ether; aromatic hydrocarbons such as benzene and toluene; alcohols such as methanol and ethanol; methylene chloride; It may be a halogenated hydrocarbon such as chloroform, carbon tetrachloride, dichloroethane, a nitrile such as acetonitrile, or an acetate such as methyl acetate, ethyl acetate or butyl acetate, and is preferably an alcohol.

The reaction temperature is usually 0 ° C. to 100 ° C. (preferably 0 ° C. to 50 ° C.), and the reaction time is usually 15 minutes to 24 hours (preferably 30 minutes to 1 hour).

The catalyst used for the catalytic reduction reaction can be palladium-carbon, platinum oxide, Raney-nickel, preferably palladium-carbon.

The solvent used is the same as in the case of the reduction reaction with phosphines.

The reaction temperature is usually 0 ° C. to 40 ° C. (preferably 0 ° C. to 30 ° C.), and the reaction time is usually 10 minutes to 24 hours (preferably 30 minutes to 3 hours).

After completion of the reaction, the target compound of this reaction is collected from the reaction mixture according to a conventional method. For example, water is added to the reaction mixture, extracted with a water-immiscible organic solvent such as methylene chloride or ethyl acetate, washed with saturated saline, dried over anhydrous magnesium sulfate, and the like, and the solvent is distilled off. Can be. Used for the next reaction without further purification.

The fifteenth step is a step for producing a compound having the general formula (XVIII), in which the compound having the general formula (XVII) is removed in an inert solvent in the presence of a catalyst to remove the protecting groups R ¹ and R ² . This is achieved by performing

The inert solvents used include alcohols such as methanol and ethanol, ethers such as diethyl ether, dioxane, tetrahydrofuran, dimethoxyethane and diglyme, methylene chloride, chloroform, carbon tetrachloride and dichloroethane. Such as halogenated hydrocarbons, aromatic hydrocarbons such as benzene and toluene, lower fatty acids such as formic acid and acetic acid, acetates such as methyl acetate, ethyl acetate and butyl acetate, N, N
Amides such as -dimethylacetamide, N, N-dimethylformamide, N-methyl-2-pyrrolidinone;
It can be a nitrile such as acetonitrile, dimethyl sulfoxide, a mixed solvent of water and the above-mentioned solvent, and preferably an alcohol (particularly ethanol).

The catalysts used include, for example, mineral acids such as hydrochloric acid, hydrobromic acid and sulfuric acid, sulfonic acids such as paratoluenesulfonic acid and camphorsulfonic acid, and organic fatty acids such as trifluoroacetic acid, acetic acid and formic acid. And preferably mineral acids, especially hydrochloric acid.

The reaction temperature is usually 0 ° C. to 100 ° C. (preferably 40 ° C. to 50 ° C.), and the reaction time is usually 5 minutes to 24 hours (preferably 5 minutes to 6 hours).

After completion of the reaction, the target compound of this reaction is collected from the reaction mixture according to a conventional method. For example, water is added to the reaction mixture, extracted with a water-immiscible organic solvent such as methylene chloride or ethyl acetate, washed with saturated saline, dried over anhydrous magnesium sulfate, and the like, and the solvent is distilled off. Can be. The obtained residue is used for the next step without purification.

The sixteenth step is a step for producing a compound having the general formula (XVI _a ), wherein the compound having the general formula (XVIII a) is protected by a hydrogenolysis reaction in an inert solvent in the presence of a catalyst in hydrogen. This is achieved by performing a removal reaction of the group R ³ .

The inert solvents used include alcohols such as methanol and ethanol, ethers such as diethyl ether, dioxane, tetrahydrofuran, dimethoxyethane and diglyme, and acetates such as methyl acetate and ethyl acetate. And lower fatty acids such as formic acid and acetic acid, preferably alcohols (especially ethanol).

The catalyst used may be palladium-carbon, palladium hydroxide-carbon (Pearlman's catalyst), preferably palladium hydroxide-carbon.

The reaction temperature is usually 0 ° C. to 100 ° C. (preferably 10 ° C. to 30 ° C.), and the reaction time is usually 15 ° C.
Minutes to 24 hours (preferably 30 minutes to 2 hours).

After completion of the reaction, the target compound of this reaction is collected from the reaction mixture according to a conventional method. For example, it can be obtained by filtering and concentrating the reaction mixture and distilling off the solvent. If necessary, it can be purified by reverse phase column chromatography or the like.

The seventeenth step is a step for producing a compound having the general formula (XVIII), wherein the compound having the general formula (XIV) is reacted with an acylating agent having the formula R ⁶ OR ⁶ or R ⁶ X in an inert solvent. Achieved by processing.

The inert solvents used are, for example, alcohols such as methanol, ethanol and isopropanol, ethers such as diethyl ether, dioxane and tetrahydrofuran, methylene chloride, chloroform, carbon tetrachloride and dichloroethane. Halogenated hydrocarbons, aromatic hydrocarbons such as benzene and toluene, acetates such as methyl acetate, ethyl acetate and butyl acetate, N, N-dimethylacetamide, N, N-
It may be an amide such as dimethylformamide, N-methyl-2-pyrrolidinone, or a nitrile such as acetonitrile, and is preferably an alcohol (particularly methanol).

The acylating agents used include, for example, acid anhydrides such as acetic anhydride, trifluoroacetic anhydride and benzoic anhydride, monochloroacetyl chloride, monobromoacetyl chloride, trichloroacetyl chloride, acetyl chloride, propionyl bromide, It may be an acid halide of a C ₂ -C ₄ fatty acid or a C ₆ -C ₁₀ arylcarboxylic acid which may be substituted with a halogen such as benzoyl chloride, and is preferably an acid anhydride (particularly, acetic anhydride). .

The reaction temperature is usually -20 ° C to 50 ° C (preferably 0 ° C to 30 ° C), and the reaction time is usually 5 minutes to 5 hours (preferably 5 minutes to 2 hours). is there.

After completion of the reaction, the target compound of this reaction is collected from the reaction mixture according to a conventional method. For example, water can be added to the reaction mixture, extracted with a water-immiscible organic solvent such as methylene chloride or ethyl acetate, washed with saturated saline, dried over anhydrous magnesium sulfate, and the like, and the solvent can be distilled off. Can be. If necessary, purify by column chromatography. However, it is used for the next reaction without further purification. The eighteenth step is a step for producing a compound having the general formula (XIX),
Is carried out in an inert solvent in the presence of a catalyst to remove the protecting groups R ¹ and R ² .

The inert solvents used include alcohols such as methanol and ethanol, ethers such as diethyl ether, dioxane, tetrahydrofuran, dimethoxyethane and diglyme, methylene chloride, chloroform, carbon tetrachloride and dichloroethane. Such as halogenated hydrocarbons, aromatic hydrocarbons such as benzene and toluene, lower fatty acids such as formic acid and acetic acid, acetates such as methyl acetate, ethyl acetate and butyl acetate, N, N
Amides such as -dimethylacetamide, N, N-dimethylformamide, N-methyl-2-pyrrolidinone;
It can be a nitrile such as acetonitrile, dimethyl sulfoxide, a mixed solvent of water and the above-mentioned solvent, and preferably an alcohol (particularly ethanol).

The catalyst used is, for example, mineral acids such as hydrochloric acid, hydrobromic acid and sulfuric acid, sulfonic acids such as paratoluenesulfonic acid and camphorsulfonic acid, and organic fatty acids such as trifluoroacetic acid, acetic acid and formic acid. And preferably mineral acids, especially hydrochloric acid.

The reaction temperature is usually 0 ° C. to 100 ° C. (preferably 40 ° C. to 50 ° C.), and the reaction time is usually 5 minutes to 24 hours (preferably 5 minutes to 6 hours).

After completion of the reaction, the target compound of this reaction is collected from the reaction mixture according to a conventional method. For example, water is added to the reaction mixture, extracted with a water-immiscible organic solvent such as methylene chloride or ethyl acetate, washed with saturated saline, dried over anhydrous magnesium sulfate, and the like, and the solvent is distilled off. Can be. If necessary, it may be purified by column chromatography, but used in the next step without purification.

The nineteenth step is a step of producing a compound having the general formula (XXII). The compound having the general formula (XIX) is prepared by reacting the compound having the formula R ⁷ OR ⁷ , R
It is accomplished by treatment with an acylating agent having ⁷ X. Inert solvents used include ethers such as diethyl ether, dioxane and tetrahydrofuran, halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride and dichloroethane, and aromatic hydrocarbons such as benzene and toluene. Hydrogens, acetates such as methyl acetate, ethyl acetate, butyl acetate, amides such as N, N-dimethylacetamide, N, N-dimethylformamide, N-methyl-2-pyrrolidinone, nitriles such as acetonitrile In particular, pyridine is used as a solvent among the following bases.

The acylating agent used can be, for example, acid anhydrides such as acetic anhydride, trifluoroacetic anhydride, benzoic anhydride, and acid halides such as acetyl chloride, propionyl bromide, benzoyl chloride. Is an acid anhydride (particularly, acetic anhydride).

The base used is, for example, a tertiary lower alkylamine such as triethylamine, ethyldiisopropylamine, tributylamine, 1,8-diazabicyclo [5.4.0] undecane-7-ene (DBU), 1,4 Tertiary alicyclic amines such as diazabicyclo [2.2.2] octane (DABCO), imidazole, diethylaniline, dimethylaniline, 4-dimethylaminopyridine,
It can be pyridine, and is preferably a tertiary lower alkylamine or a tertiary alicyclic amine (particularly, pyridine).

The reaction temperature is usually -20 ° C to 50 ° C (preferably 0 ° C to 30 ° C), and the reaction time is usually 5 minutes to 5 hours (preferably 5 minutes to 2 hours). is there.

After completion of the reaction, the target compound of this reaction is collected from the reaction mixture according to a conventional method. For example, water is added to the reaction mixture, extracted with a water-immiscible organic solvent such as methylene chloride or ethyl acetate, washed with saturated saline, dried over anhydrous magnesium sulfate, and the like, and the solvent is distilled off. Can be. If necessary, purify by column chromatography. However, it is used for the next reaction without further purification. The twentieth step is represented by the formula (XXII)
In the step of producing the compound having the formula (I), the compound represented by the general formula (XXI)
This is achieved by subjecting the compound having I) to a reaction of removing the protecting group R ³ by hydrogenolysis in hydrogen in the presence of a catalyst in an inert solvent.

The inert solvents used include alcohols such as methanol and ethanol, ethers such as diethyl ether, dioxane, tetrahydrofuran, dimethoxyethane and diglyme, and acetates such as methyl acetate and ethyl acetate. And lower fatty acids such as formic acid and acetic acid, preferably alcohols (especially ethanol).

The catalyst used may be palladium-carbon, palladium hydroxide-carbon (Pearlman's catalyst), preferably palladium hydroxide-carbon.

The reaction temperature is usually 0 ° C. to 100 ° C. (preferably 10 ° C. to 30 ° C.), and the reaction time is usually 15 ° C.
Minutes to 24 hours (preferably 30 minutes to 2 hours).

After completion of the reaction, the target compound of this reaction is collected from the reaction mixture according to a conventional method. For example, the reaction mixture is filtered, concentrated, extracted with a water-immiscible organic solvent such as methylene chloride or ethyl acetate, washed with water and then with saturated saline, dried over anhydrous magnesium sulfate, and the like, and the solvent is distilled off. Can be obtained. If necessary, it can be further purified by a conventional method, for example, column chromatography or the like.

The twenty-first step is a step of producing a compound having the formula (XVI _a ), in which the R ⁶ and R ⁷ groups are removed from the compound having the formula (XXIII) in an inert solvent in the presence of a base catalyst. Achieved by:

The inert solvent used may be alcohols such as methanol and ethanol, ethers such as diethyl ether, dioxane and tetrahydrofuran, pyridine, triethylamine, and a mixed solvent of water and the above solvents. Are alcohols (particularly methanol).

The catalyst used is, for example, an alkali metal hydroxide such as sodium hydroxide, potassium hydroxide or lithium hydroxide; an alkali metal carbonate such as sodium carbonate or potassium carbonate; sodium hydrogen carbonate; An alkali metal bicarbonate, such as potassium,
Preferably, it is an alkali metal hydroxide (particularly potassium hydroxide). The reaction temperature is usually 0 ° C to 100 ° C (preferably 0 ° C to 30 ° C), and the reaction time is usually 5 minutes to 24 hours (preferably 5 minutes to 15 hours).

After completion of the reaction, the target compound of this reaction is the first compound
A sample is collected from the reaction mixture by the same treatment as in the six steps.

The twenty-second step is a step for producing a compound having the general formula (XXIV). The compound having the general formula (XXIII) is prepared by reacting the compound having the formula R ⁷ OR
⁷ , which is achieved by treatment with an acylating agent having R ⁷ X.

This step is performed by the same operation as in the nineteenth step.

The twenty-third step is a step for producing a compound having the formula (XVI _a ), in which the R ⁶ and R ⁷ groups are removed from the compound having the formula (XXIV) in an inert solvent in the presence of a base catalyst. Achieved by:

By the steps described above, aminopentane cyclitol (XV _b , XV _c , XV _d ) corresponding to azidopentane cyclitol (I _b , I _c , I _d ) can be produced.

[0137]

【Example】

Example 1 Anti- and Syn- (2R, 3S, 4R) -4-benzo
Yloxy-2,3-dimethoxymethoxy-5-hexe
Synthesis of nal oxime 2R, 3S, 4R) -4-Benzoyloxy-2,3-
5.36 g of dimethoxymethoxy-5-hexenal (19.3 mmo
l) was dissolved in 100 ml of diethyl ether, followed by aqueous hydroxyamine hydrochloride solution (13.4 g of hydroxyamine hydrochloride).
(193 mmol) was dissolved in 53.5 ml of distilled water. ) Was dropped into the reaction system at room temperature. After completion of the dropwise addition, an aqueous sodium carbonate solution (20.4 g (193 mmol) of sodium carbonate was added to distilled water 40).
(dissolved in 1 ml) was dropped into the system at room temperature, and after completion of dropping, the mixture was stirred at room temperature for 8 hours. After confirming the completion of the reaction, the reaction solution was separated and extracted twice with 200 ml of diethyl ether, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was washed with diethyl ether. Concentrated. The obtained concentrated residue was purified by silica gel column chromatography (Kieselgel-60; 350 g, developing solvent system: benzene / ethyl acetate = 3/1) to give the desired oxime anti-isomer (3.67 g, yield 53.9). %, 1.19 g of the syn-form was obtained in a colorless and transparent syrup in a yield of 17.5%.

[0138]Anti body 270MHz¹H-NMR (CDCl_Three) δ (ppm): 8.15-8.05 (m, 2H), 7.65-
7.54 (m, 1H), 7.51-7.40 (m, 3H), 7.36 (s, 1H), 5.82 (t, 1H, J =
5.6Hz), 5.44 (d, 1H, J = 17.2Hz), 5.34 (d, 1H, J = 10.6Hz), 4.8
5,4.77,4.73 and 4.66 (each d, 1H × 4, J = 6.6Hz), 4.45 (d
d, 1H, J = 7.6Hz, J = 5.6Hz), 3.99 (t, 1H, J = 5.6Hz), 3.42 and
3.41 (each s, 3H × 2) IR (liquid film) (cm^-1): 3391,2897,1725,1602,1269,115
1,1106,1070,1025,922,713 Rf value; 0.38 (Developing solvent system: benzene / ethyl acetate = 3 /
1)Shin body 270MHz¹H-NMR (CDCl_Three) δ (ppm): 8.08 (d, 2H, J = 7.9Hz), 7.7
3 (bs, 1H), 7.65-7.35 (m, 3H), 6.92 (d, 1H, J = 5.9Hz), 6.12-
5.95 (m, 1H), 5.82 (t, 1H, J = 5.9Hz), 5.49 (d, 1H, J = 15.8Hz),
5.37 (d, 1H, J = 10.6Hz), 5.12 (dd, 1H, J = 5.9Hz, J = 3.0Hz), 4.
87-4.60 (m, 4H), 4.21 (dd, 1H, J = 5.9Hz, J = 3.0Hz), 3.46 and
 3.35 (each s, 3H × 2) IR (liquid filim): 3374,2896,1723,1602,1271,1152,110
8,1071,1026,921,713 Rf value; 0.26 (Developing solvent system; benzene / ethyl acetate = 3 /
1) Example 2[3aR- (3aα, 4α, 5β, 6α)]-4-ben
Zoyloxy-5,6-dimethoxymethoxy-3,3
a, 5,6-Tetrahydro-4H-cyclopent [C]
Synthesis of isoxazole Anti body 3.59 g (10.1 mmol), triethylamine 0.14 ml
(1.0 mmol) in 180 ml of methylene chloride solution 5% hypochlorous acid
57 ml of aqueous sodium acid solution was slowly added dropwise while stirring with ice water.
After the addition is complete, stir for 40 minutes under ice cooling.
Was. After confirming the completion of the reaction, the reaction mixture was diluted with 200 ml of methylene chloride.
Batch extraction was performed, and the obtained organic phase was washed with a saturated saline solution.
After drying over anhydrous magnesium sulfate, filtration and filtration of the residue were performed.
After washing with styrene, the filtrate and washing solution are combined and concentrated under reduced pressure.
Was.

The obtained concentrated residue was purified by silica gel column chromatography (Kieselgel-60; 300 g, developing solvent system; hexane / ethyl acetate = 3/1) to give the desired compound (isoxazoline compound ) as a white solid. , 2.37g,
Obtained in 66.4% yield. On the other hand, 1.13 g (3.2 mmol) of syn-body
To a solution of 0.044 ml (0.32 mmol) of triethylamine in 56 ml of methylene chloride, 18 ml of a 5% aqueous sodium hypochlorite solution was gradually added dropwise with cooling with ice water, and after the addition was completed, the mixture was stirred for 40 minutes with cooling with ice water. did. After confirming the completion of the reaction,
The reaction solution was separated and extracted twice with 100 ml of methylene chloride, and the obtained organic phase was washed with saturated saline, dried over anhydrous magnesium sulfate, filtered, and the residue was washed with methylene chloride, and the filtrate and the washing solution were washed. And concentrated under reduced pressure.

[0140] The resulting concentrated residue was purified by silica gel column chromatography (Kieselgel -60; 100 g, developing solvent system: hexane / ethyl acetate = 3/1) to obtain the desired
0.7314 g of compound (isoxazoline compound ) as white solid, yield
Obtained at 65.1%.

270 MHz ¹ H-NMR (CDCl ₃ ) δ (ppm): 8.04 (d, 2H,
J = 7.3Hz), 7.61 (t, 1H, J = 7.3Hz), 7.47 (t, 2H, J = 7.3Hz), 4.9
-4.64 (m, 8H), 4.43 (dd, 1H, J = 9.2Hz, J = 11.9Hz), 3.91 (dt, 1
H, J = 11.0Hz, J = 9.2Hz), 3.45 and 3.40 (s, 3H × 2 each) IR (KBr disk): 2990,2951,2934,2901,2822,1728,1452,12
78,1154,1125,1051,1033,1024,713 Rf value; 0.43 (Developing solvent system; hexane / ethyl acetate = 3 /
1) Example 3 (4S, trans) -4,5-dimethoxymethoxy-
2-hydroxymethyl-2-cyclopenten-1-one
0.99 m of synthetic isoxazoline body 5.00 g (14.2 mmol) in methanol
l, dissolved in a mixed solvent of 50 ml of 1.4-dioxane and 30 ml of distilled water, and 4.4 g (71 mmol) of boric acid was added to the system.
5.0 ml of Raney nickel heated under reflux with stirring for 5 hours were added under ice-water cooling, and the mixture was added under a hydrogen atmosphere at normal pressure and room temperature.
Stirred for hours. After confirming the completion of the reaction, the reaction solution was filtered through celite, the residue was washed with methanol, the filtrate and the washings were concentrated under reduced pressure, and the obtained concentrated residue was washed twice with 300 ml of methylene chloride.
Separation extraction was performed with 200 ml of saturated aqueous sodium hydrogen carbonate, and the organic phase was washed with saturated saline.

The obtained organic phase was dried over anhydrous magnesium sulfate, filtered, and the residue was washed with methylene chloride. The filtrate and washings were combined, concentrated, and the concentrated residue was subjected to silica gel column chromatography (Kieselgel-60). ; 400 g, developing solvent; benzene / ethyl acetate = 1/2)
The target compound enone compound is converted into a pale yellow transparent syrup 2.
36 g was obtained at a yield of 71.5%.

270 MHz ¹ H-NMR (CDCl ₃ ) δ (ppm): 7.32 (q, 1H,
J = 1.8Hz), 4.98,4.88,4.85,4.80 (d, 1H × 4, J = 6.7H respectively
z), 4.69 (quintet, 1H, J = 1.8Hz), 4.43-4.36 (m, 2H, H-6,
6 '), 4.29 (d, 1H, J = 1.8Hz), 3.47 and 3.45 (s, 3H ×
2), 2.12 (t, 1H, J = 5.9 Hz) IR (Neat) (cm ^-1 ): 3460, 2900, 1725, 1215, 1155, 1114, 1040 Rf value; 0.45 (Developing solvent: benzene / ethyl acetate = 1/2
Example 4 (4S-trans) -2- (t-butyldimethylsilyl)
Xy) methyl-4,5-dimethoxymethoxy-2-cycl
Synthesis of lopenten-1-one 2.15 g (9.3 mmol) of the enone compound was treated with anhydrous dimethylformamide.
Dissolve in 45 ml at room temperature, add 2.08 g (14.0 mmol) of t-butyldimethylsilane chloride and 0.96 g (14.1 mmol) of imidazole into the system under ice water cooling and stirring, and raise the temperature from ice water cooling to water cooling. And stirred overnight.

After confirming the completion of the reaction, 0.68 ml of methanol was introduced into the system.
, And the mixture was stirred for 30 minutes. The reaction solution was separated and extracted twice with 150 ml of ethyl acetate and saturated saline, and the organic phase was dried over anhydrous magnesium sulfate. And washed.

The obtained filtrate and washings were concentrated under reduced pressure, the concentrated residue was dried under reduced pressure, and purified by silica gel column chromatography (Kieselgel-60; 300 g, developing solvent: hexane / ethyl acetate = 4/1). Then, the target compound was obtained in a colorless and transparent syrup at 2.82 g in a yield of 87.9%.

270 MHz¹H-NMR (CDCl_Three) δ (ppm): 7.28 (q, 1H,
J = 2.1Hz), 4.96,4.86,4.82, and 4.78 (each d, 1H × 4, J = 5.
9Hz), 4.64 (quintet, 1H, J = 2.1Hz), 4.36 (q, 2H, J = 2.1Hz),
4.26 (d, 1H, J = 2.1Hz), 3.46 and 3.42 (s, 3H × 2 each), 0.
90 (s, 9H), 0.07 (s, 6H) IR (Neat) (cm^-1): 2960,2940,2900,2860,1724,1465,1400,
1382,1290,1260,1218,1158,1040,1005,950,920,840,780 Rf value; 0.85 (Developing solvent; hexane / ethyl acetate = 1/1
 Example 5[1R- (1β, 4β, 5α)]-2- (t-butyldi
Methylsilyloxy) methyl-4,5-dimethoxymethoxy
C-2-cyclopenten-1-ol and [1S- (1
α, 4α, 5α)]-2- (t-butyldimethylsilylo
Kiss )Methyl-4,5-dimethoxymethoxy-2-cycl
Synthesis of Lopenten-1-ol 2.67 g (7.7 mmol) of the compound of Example 4 was added to 55 ml of methanol.
Dissolve at room temperature, and in the system cool with ice water cooling
4.5 g (12.1 mmol) were added and stirred for 30 minutes.
Was.

Next, 0.45 g of sodium borohydride (11.9 m
mol) was gradually added to the system under ice water cooling and stirring, and the mixture was stirred as it was under ice cooling for 2 hours.

After confirming the completion of the reaction, 10%
(V / v) 6 ml of an acetic acid-methanol solution was added, and the mixture was stirred for 15 minutes. Then, the reaction solution was extracted twice with 200 ml of ethyl acetate, and separated and extracted with 100 ml of a saturated aqueous sodium hydrogen carbonate solution. The extract was washed with saturated saline, dried over anhydrous magnesium sulfate, filtered, and the residue was washed with ethyl acetate. The filtrate and washings were combined, concentrated under reduced pressure, and the concentrated residue was purified by silica gel column chromatography (Kieselgel-60; 600 g, developing solvent: benzene / ethyl acetate = 3/1) to obtain the 1R-isomer.
1.41 g, 52.5% yield and 0.56 g of 1S-isomer, 20.8% yield
Were each obtained in a colorless and transparent syrup.

1R- isomer 270 MHz ¹ H-NMR (CDCl ₃ ) δ (ppm): 5.75 to 5.70 (m, 1H, H-3), 4.
80 (s, 2H), 4.79 and 4.72 (d, 1H × 2, J = Hz respectively), 4.50-
4.41 (m, 2H), 4.41-4.22 (m, 2H), 3.88 (t, 1H, J = 5.1Hz), 3.47
and 3.39 (each s, 3H × 2), 3.46 (d, 1H, J = 4.6Hz), 0.92
(s, 9H), 0.09 (s, 6H) IR (Neat) (cm ^-1 ): 3460,2980,2890,2850,1650,1460,1400,
1370,1360,1258,1150,1100,1040,940,918,840,780 1S- body _{^{270MHz 1 H-NMR (CDCl 3}} ) δ (ppm): 5.39-5.30 (m, 1H), 4.82,
4.78,4.77 and 4.72 ((each d, J = 6.3Hz), 4.73-4.66 (m, 1
H), 4.62 (t, 1H, J = 4.7Hz), 4.42-4.22 (m, 2H), 4.07 (dd, 1H, J
= 6.1Hz, J = 4.7Hz), 3.45 and 3.39 (s, 3H × 2), 2.66
(d, 1H, J = 4.7Hz), 0.92 (s, 9H), 0.08 (s, 6H) IR (Neat) (cm ^-1 ): 3450,2930,2900,2850,1710,1460,1360,
1250,1220,1150,1100,1040,1000,920,840,780 Rf value; 0.49 [(1S) -form] (Developing solvent: benzene / ethyl acetate = 3/1) 0.40 [(1R) -form] (Developing solvent: benzene) / Ethyl acetate = 3
/ 1) Example 6 [ (3S- (3β, 4α, 5β) -5-benzyloxy-
3,4-dimethoxymethoxy-1-hydroxymethyl-
Synthesis of 1-cyclopentene 1.41 g (4.0 mmol) of the 1R- form of the compound of Example 5 was dissolved in 28 ml of anhydrous dimethylformamide, and the solution was stirred under cooling with ice water.
55% sodium hydride 0.27 g (6.0 mmol), benzyl bromide
1.0 ml (8.4 mmol) were added sequentially, and the mixture was cooled to 1 under ice-water cooling.
Stirred for hours. After confirming the completion of the reaction, add 0.37 methanol in the system.
ml was added and stirred for 30 minutes.

The reaction solution was separated and extracted twice with 100 ml of ethyl acetate and 100 ml of saturated saline, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and the residue was washed with ethyl acetate. The filtrate and washings were combined, concentrated under reduced pressure, the concentrated residue was dried under reduced pressure, and silica gel column chromatography (Kieselgel-60; 200 g, developing solvent: hexane / ethyl acetate =
The compound was purified by 5/1) to give 1.33 g of the compound in a yield of 75.1% in a colorless and transparent syrup.

This compound was treated with anhydrous tetrahydrofuran (26 ml).
At room temperature, and 3.64 ml of a tetrabutylammonium fluoride-tetrahydrofuran solution (1 M solution) was added to the system under ice water cooling and stirring, followed by stirring for 1 hour under ice water cooling.

After confirming the completion of the reaction, ice chips were added to the system, the reaction solution was extracted twice with 100 ml of ethyl acetate and separated with 100 ml of saturated saline, and the organic phase was dried over anhydrous magnesium sulfate.
Filtration and the residue were washed with ethyl acetate.

The filtrate and washings were concentrated under reduced pressure, and the resulting concentrated residue was subjected to silica gel column chromatography (Kieselgel-60; 200 g, developing solvent: hexane / ethyl acetate = 1).
/ 1) to purify the target compound with a colorless transparent syrup.
7647 g, yield 77.7%.

270 MHz ¹ H-NMR (CDCl ₃ ) δ (ppm): 7.40-7.25
(m, 5H), 5.84 (bs, 1H), 4.85,4.77,4.75and 4.72 (each d, 1
H × 4, J = 6.3Hz), 4.78 and 4.62 (each, d, 1H × 2, J = 11.6H
z), 4.47-4.40 (m, 2H), 4.31 (t, 1H, J = 4.2Hz), 4.31-4.15 (m,
2H), 3.44 and 3.40 (s, 3H × 2 each), 1.95 (bs, 1H) IR (Neat) (cm ^-1 ): 3470,2950,2900,1502,1460,1400,1360,
1310,1250,1215,1155,1100,1040,950,920,840,740,700 Rf value; 0.38 (Developing solvent; hexane / ethyl acetate = 1/1
Example 7 [1R- (1α, 2β, 3α, 4β, 5α)]-2-B
Benzyloxy-3,4-dimethoxymethoxy-1-hydro
Xymethyl-6-oxabicyclo [3.1.0] hexa
In 15 ml of anhydrous methylene chloride, at −25 ° C. under nitrogen flow, 0.33 ml (1.3 mmol) of tetraisopropyl orthotitanate, L
0.28 ml (1.3 mmol) of diisopropyl tartrate is added dropwise,
Stirred for minutes.

Next , 0.2944 g of the compound of Example 6 (0.9 mmo
l) was dissolved in 5 ml of anhydrous methylene chloride, and the solution was added dropwise to the system at -25 ° C under a nitrogen stream, followed by stirring for 20 minutes.

Then, 0.6 ml of a t-butyl hydroperoxide-toluene solution (3M solution) was added under a nitrogen stream.
The mixture was dropped into the system at -25 ° C and stirred for 4 hours. After confirming the completion of the reaction, the reaction solution was poured into 100 ml of diethyl ether under ice cooling, and then 50 ml of 10% sodium hydroxide-saturated saline was added, followed by stirring for 15 minutes.

The reaction solution was diluted with 100 ml of diethyl ether.
Batch extraction was performed, and the obtained organic phase was washed with saturated saline,
After drying over anhydrous magnesium sulfate, the mixture was filtered and the residue was washed with diethyl ether.

The filtrate and washing solution were combined and concentrated under reduced pressure. The concentrated residue was subjected to silica gel column chromatography (Kieselgel-60; 50 g, developing solvent: hexane / ethyl acetate = 1 /
Purification was performed in 2) to obtain 0.2890 g of the target compound (epoxy compound ) as a colorless transparent syrup in a yield of 93.6%.

270 MHz ¹ H-NMR (CDCl ₃ ) δ (ppm): 7.42-7.27
(m, 5H), 4.77 and 4.58 (each d, 1H × 2, J = 11.8Hz), 4.76,
4.73,4.67 and 4.56 (each d, 1H × 4, J = 6.6Hz), 4.16 (s, 1
H), 4.12 (s, 1H), 4.11 (dd, 1H, J = 12.5Hz, J = 6.6Hz), 3.96 (s, 1H
1H), 3.90 (dd, 1H, J = 12.5Hz, J = 6.6Hz), 3.67 (s, 1H), 3.41a
nd 3.37 (each s, 3H × 2), 1.90 (t, 1H, 6.6Hz) IR (Neat) (cm ^-1 ): 3460,2950,2900,1500,1455,1400,1360,
1260,1150,1040,920,740,700 Rf value; 0.36 (Developing solvent: hexane / ethyl acetate = 1/2
Example 8 [1R- (1α, 2β, 3α, 4β, 5β)]-5-A
Zid-2-benzyloxy-3,4-dimethoxymethoxy
-1-hydroxymethyl-cyclopentan-1-ol
Compound of Example 7 of 0.289g of (0.85 mmol) was dissolved in anhydrous dimethylformamide 14.5 ml, sodium azide 0 in the system.
6641 g (10.2 mmol) and ammonium chloride 0.5513 g (10.3 mmo
l) was added and the mixture was stirred in an oil bath at 125 ° C for 3 days.

After confirming the completion of the reaction, the reaction solution was diluted with 100 mL of ethyl acetate.
After extracting twice with ml, the mixture was separated and extracted with 100 ml of saturated saline, and the obtained organic phase was dried over anhydrous magnesium sulfate, filtered, and the residue was washed with ethyl acetate. The filtrate and washings were combined and concentrated under reduced pressure. The concentrated residue was dried under reduced pressure, and purified by silica gel column chromatography (Kieselgel-60; 45 g, developing solvent; hexane / ethyl acetate = 1/2).
0.2561 g of 5-azide in a pale yellow transparent syrup, yield
Obtained at 78.7%.

270 MHz ¹ H-NMR (CDCl ₃ ) δ (ppm): 7.45-7.27
(m, 5H), 4.80,4.77,4.72 and 4.68 (each d, 1H × 4, J = 6.3
Hz), 4.77 and 4.60 (each d, 1H × 2, J = 10.5Hz), 4.18 (dd, 1
H, J = 5.3Hz, J = 4.2Hz), 4.13 (t, 1H, J = 4.2Hz), 3.97 (dd, 1H, J
= 11.6Hz, J = 5.0Hz), 3.95 (d, 1H, J = 5.3Hz), 3.83 (d, 1H, J = 4.
2Hz), 3.81 (dd, 1H, J = 11.6Hz, J = 8.4Hz), 3.52 (bs, 1H), 3.43
and 3.41 (each s, 3H × 2), 2.39 (bs, 1H) IR (Neat) (cm ^-1 ): 3400,2950,2850,2100,1440,1240,1150,
1100,1030,970 Rf value; 0.54 (Developing solvent: hexane / ethyl acetate = 1/2
Example 9 [1R- (1α, 2β, 3α, 4β, 5β)]-5-A
Cetylamino-2-benzyloxy-3,4-dimethoxy
Cymethoxy-1-hydroxymethyl-cyclopentane-
Synthesis of 1-ol 61.6 mg (0.16 mmol) of the compound of Example 8 was added to 6.2 ml of methanol.
After adding 14 mg of 10% palladium carbon to the system, the mixture was stirred under a hydrogen atmosphere at normal pressure and room temperature for 2 hours. After confirming the completion of the reaction, the reaction solution was filtered, and the residue was washed with methanol.

The filtrate and the washing solution were combined, and 75.8 μl of acetic anhydride was poured into this solution at room temperature, followed by stirring for 1 hour.

After confirming the completion of the reaction, the reaction solution was concentrated under reduced pressure, and the residue was azeotroped twice with toluene.

The resulting concentrated residue was dried under reduced pressure, and then subjected to silica gel column chromatography (Kieselgel-60; 15).
g, developing solvent: methylene chloride / methanol = 18/1), and the target compound was obtained as a colorless transparent syrup in 51 mg yield.
Obtained at 79.3%.

270 MHz ¹ H-NMR (CDCl ₃ ) δ (ppm): 7.45-7.25
(m, 5H), 6.25 (d, 1H, J = 6.6Hz), 4.81, and 4.67 (each d, 1H
× 2, J = 7.4Hz), 4.74 and 4.72 (each d, 1H × 2, J = 2.6Hz),
4.71and 4.59 (each d, 1H × 2, J = 11.9Hz), 4.42 (dd, 1H, J =
6.6Hz, J = 4.2Hz), 4.27 (t, 1H, J = 6.6Hz), 4.16 (t, 1H, J = 4.2H
z), 3.89 (s, 1H), 3.81 (dd, 1H, J = 11.6Hz, J = 5.3Hz), 3.80 (d,
1H, J = 4.2Hz), 3.57 (dd, 1H, J = 11.6Hz, J = 8.4Hz), 3.43 and
3.40 (each s, 3H × 2), 2.05 (s, 3H), 1.71 (bs, 1H) IR (KBr) (cm ^-1 ): 34333,3296,3206,3076,2947,2895,1653,
1560,1216,1147,1112,1044 Rf value: 0.43 (Developing solvent: methylene chloride / methanol = 18
/ 1) Example 10 [(1R- (1α, 2β, 3α, 4β, 5β) -5-A
Cetylamino ] -1,3,4-triacetoxy-1-a
Of Sethoxymethyl-2-benzyloxy-cyclopentane
49.5 mg of the compound of Synthesis Example 9 was dissolved in 0.74 ml of methanol at room temperature, and 0.74 ml of a 10% hydrochloric acid gas-methanol solution was added into the system.
Was added and stirred in a 50 ° C. oil bath for 10 minutes. After confirming the completion of the reaction, the reaction solution was concentrated under reduced pressure, and the concentrated residue was dried under reduced pressure.

The obtained crude product was dissolved in anhydrous pyridine (2.0 ml), acetic anhydride (0.5 ml) and 4-dimethylaminopyridine (1.5 mg) were added at room temperature, and the mixture was stirred at room temperature overnight.

After confirming the completion of the reaction, the reaction solution was concentrated under reduced pressure, the residue was azeotropically distilled with toluene, then extracted twice with 50 ml of ethyl acetate, and then separated and extracted with a saturated saline solution. Was dried over anhydrous magnesium sulfate, filtered, and the residue was washed with ethyl acetate.

The filtrate and washings were concentrated under reduced pressure, and the concentrated residue was subjected to silica gel column chromatography (Kieselgel-60;
15 g, developing solvent: benzene / acetonitrile = 2/1)
44.1 mg of the target compound in a colorless transparent syrup,
Obtained at a yield of 74.2%.

270 MHz ¹ H-NMR (CDCl ₃ ) δ (ppm): 7.50-7.28
(m, 5H), 6.00 (d, 1H, J = 11.2Hz), 5.46 (dd, 1H, J = 6.9Hz, J = 4.
6Hz), 5.22 (d, 1H, J = 4.6Hz), 5.09 (ddd, 1H, J = 11.2Hz, J = 6.9
Hz, J = 1.6Hz), 4.87 and 4.65 (each d, 1H × 2, J = 11.9Hz),
4.77 and 4.70 (each d, 1H × 2, J = 12.5Hz), 4.47 (bs, 1H),
2.07,20.4,1.91 (each s, 3H × 3), 2.05 (s, 3H × 2) IR (Neat) (cm ^-1 ): 3360,3060,3040,2980,2870,1720,1682,
1520,1365,1220,1046752,700,600 Rf value; 0.44 (Developing solvent: benzene / acetonitrile = 1
/ 11) Example 11 [(1R- (1α, 2β, 3α, 4β, 5β)]-5-
Acetylamino-1,2,3,4-tetraacetoxy-
Synthesis of 1-acetoxymethyl-cyclopentane 69.5 mg (0.14 mmol) of the compound of Example 10 was added to methanol 7.
Then, 0.41 g of palladium hydroxide-carbon was added to the system, and the mixture was stirred under a hydrogen atmosphere at normal pressure and room temperature for 1 hour.
After confirming the completion of the reaction, the reaction solution was filtered, the residue was washed with ethanol, the filtrate and the washing were combined and concentrated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (Kieselgel-60; 150 g, developing solvent; Purification with benzene / acetonitrile = 1/1) gave 47.8 mg of the debenzylated product.
47.8 mg of the debenzylated product was dissolved in 2.4 ml of anhydrous pyridine, and 0.24 ml of acetic anhydride and 5.0 ml of 4-dimethylaminopyridine were dissolved.
g was added and stirred at room temperature overnight.

After confirming the completion of the reaction, add 0.5 ml of ethanol to the system.
Was added and stirred for 30 minutes. Next, the reaction solution was concentrated under reduced pressure, and the residue was azeotropically distilled with toluene.
Twice with 1N-hydrochloric acid 50ml, saturated aqueous sodium bicarbonate 50ml, saturated saline
Liquid separation was sequentially performed with 50 ml, and the obtained organic phase was dried over anhydrous magnesium sulfate, filtered, and the residue was washed with ethyl acetate.

The filtrate and washings were combined and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (Kieselgel-60; 5.0 g, developing solvent: benzene / acetonitrile = 3/2) to give the desired compound. A colorless, transparent syrup was obtained in 37.4 mg, 2 step yield; 60.6%.

270 MHz ¹ H-NMR (CDCl ₃ ) δ (ppm): 5.89 (d, 1H,
J = 8.5Hz), 5.81 (d, 1H, J = 4.9Hz), 5.38 (dd, 1H, J = 8.5Hz, J =
4.9Hz), 5.33 (t, 1H, J = 8.5Hz), 5.24 (t, 1H, J = 4.9Hz), 4.63
And 4.56 (2H, J = 11.9Hz each) 2.14,2.13,2.09,2.08,2.0
7 and 2.02 (s, 3H × 6 each) FT-IR (KBr disk) (cm ^-1 ): 3367,1744,1726,1695,1527,145
8,1434,1369,1235,1103,1063,1045 Rf value; 0.34 (Developing solvent: benzene / acetonitrile = 2
/ 1)

──────────────────────────────────────────────────続 き Continuation of front page (56) References Am. Chem. Soc. , Vol. 114, No. 25 (December 1992) p. 10065-10066 (58) Field surveyed (Int. Cl. ⁷ , DB name) CA (STN) REGISTRY (STN)

Claims (5)

(57) [Claims] 1. A compound of the general formula (I) [Wherein, R ¹ and R ² are the same or different and C ₁ -C
₄ alkoxymethyl groups, C ₁ -C ₄ alkoxy C ₁ -C
_{4 represents an} alkoxymethyl group or a C ₇ -C ₁₁ aralkyloxymethyl group, and R ³ represents a C ₇ -C ₁₁ aralkyl group. Azidopentane cyclitol represented by the formula: 2. A compound of the general formula [Wherein, R ¹ and R ² are the same or different and C ₁ -C
₄ alkoxymethyl groups, C ₁ -C ₄ alkoxy C ₁ -C
₄ alkoxymethyl a methyl group or a C ₇ -C ₁₁ aralkyloxy methyl, R ⁴ represents a C ₂ -C ₅ aliphatic alkanoyl or C ₇ -C ₁₁ aromatic alkanoyl groups. ]
An aldehyde compound represented by the formula is reacted with hydroxyamine to give a compound of the general formula [Wherein, R ¹ , R ² and R ⁴ have the same meanings as described above. The oxime compound (III) represented by the general formula is reacted with an oxidizing agent in the presence of a base to carry out a cyclization reaction. [Wherein, R ¹ and R ² have the same meanings as described above. ]
An oxazoline compound represented by the formula is produced, and oxazoline (IV) is subjected to a hydrogenolysis reaction in the presence of a transition metal catalyst, and is hydrolyzed and ring-opened in the presence of an acid catalyst to obtain a compound represented by the general formula: [Wherein, R ¹ and R ² have the same meanings as described above. ]
A cyclopentenone compound represented by the general formula R ⁵ X is prepared by preparing a cyclopentenone compound (V) in the presence of a base.
(VI) [wherein, R ⁵ represents a tri-C ₁ -C ₄ alkylsilyl group or a di-C ₁ -C ₄ alkylmonoC ₆ -C ₁₀ arylsilyl group, and X represents a halogen atom. With a protecting agent for a hydroxyl group represented by the general formula: [Wherein, R ¹ , R ² and R ⁵ are as defined above. And the cyclopentenone compound (VII) is reacted with a reducing agent in the presence of a catalyst to give a compound of the general formula [Wherein, R ¹ , R ² and R ⁵ are as defined above. To produce a cyclopentenol compound represented by the general formula R ³ X (IX) in the presence of a base, wherein R ³ is C ₇ -C
₁₁ represents an aralkyl group, and X has the same meaning as described above. With a hydroxyl-protecting agent represented by the general formula: [Wherein, R ¹ , R ² , R ³ and R ⁵ have the same meaning as described above. Is produced by reacting the cyclopentene compound (X) with a silyl group-cleaving agent to carry out a deprotection group reaction of a trialkylsilyl group. [Wherein, R ¹ , R ² and R ³ have the same meanings as described above. Wherein the cyclopentenol compound (XI) is reacted with an oxidizing agent to give a cyclopentenol compound represented by the formula: [Wherein, R ¹ , R ² and R ³ have the same meaning as described above. Wherein the epoxy compound (XIIα) is treated with an azidating agent in the presence of an acid catalyst. [Wherein, R ¹ , R ² and R ³ have the same meaning as described above. ]
A method for producing an azidopentane cyclitol compound represented by the formula: 3. A compound of the general formula produced in the eighth step described above. [Wherein, R ¹ , R ² and R ³ have the same meaning as described above. Wherein the epoxy compound (XIIβ) is treated with an azidating agent in the presence of an acid catalyst. [Wherein, R ¹ , R ² and R ³ have the same meaning as described above. ]
A method for producing an azidopentane cyclitol compound represented by the formula: 4. The general formula produced in the fifth step described above: [Wherein, R ¹ , R ² and R ⁵ are as defined above. The cyclopentenol compound (VI
IIα) in the presence of a base in the general formula R ³ X (IX)
R ³ represents a C ₇ -C ₁₁ aralkyl group, and X has the same meaning as described above. With a protecting agent for a hydroxyl group represented by the general formula: [Wherein, R ¹ , R ² , R ³ and R ⁵ have the same meaning as described above. The cyclopentene compound (XIII) is reacted with a silyl group cleaving agent, and a dealkylation reaction of a trialkylsilyloxymethyl group is carried out to produce a cyclopentene compound represented by the general formula: [Wherein, R ¹ , R ² and R ³ have the same meanings as described above. Wherein the cyclopentenol compound (XI) is reacted with an oxidizing agent to obtain a cyclopentenol compound represented by the formula: [Wherein, R ¹ , R ² and R ³ have the same meaning as described above. Wherein the epoxy compound (XVα) is treated with an azidating agent in the presence of an acid catalyst. [Wherein, R ¹ , R ² and R ³ have the same meaning as described above. ]
A method for producing an azidopentane cyclitol compound represented by the formula: 5. The general formula produced in the above-mentioned thirteenth step: [Wherein, R ¹ , R ² and R ³ have the same meaning as described above. Wherein the epoxy compound (XVβ) represented by the general formula is treated with an azidating agent in the presence of an acid catalyst. [Wherein, R ¹ , R ² and R ³ have the same meaning as described above. ]
A method for producing an azidopentane cyclitol compound represented by the formula: