JPH11130765A - Epoxyethane derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new compound useful as a synthetic intermediate for an epolactaene and its derivative used as an antitumor agent or a neuronal differentiation inducer. SOLUTION: This compound is represented by formula I (R<1> is a 1-6C alkyl or the like; R<2> is H or the like; R<3> is a 1-6C alkoxy or the like; R<4> is a 1-6C alkoxy or the like), e.g. di(t-butyl) 3-(1-hydroxyethyl)oxirane-2,2-dicarboxylate. The compound represented by formula I is obtained by removing the protecting group of hydroxyl group in, e.g. a compound represented by formula II (W<2> is the protecting group of the hydroxyl group; X<1> is a halogen; R<3a> and R<4a> denote each the same meaning as that of the alkoxy when R<3> and R<4> denote each the 1-6C alkoxy) [e.g. di(t-butyl) 2-(1,2-bistrimethylsilyloxypropyl)-2- iodomalonate] in the presence of ethers such as tetrahydrofuran with tetrabutylammonium fluoride or the like and carrying out an epoxidizing reaction.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to an antitumor agent used for the treatment of nerve tumors and the like, and to epolactaene and its derivatives, which are regarded as promising agents for inducing neuronal differentiation for use in the treatment and / or prevention of neurological diseases and the like. Related to synthetic intermediates.

[0002]

2. Description of the Related Art Epolactaene is an actinomycete BM1689-P isolated from the seabed soil of Uchiura Bay by Nagata et al.
It is a natural organic compound isolated from the culture solution in which the strain was cultured, and has the following structural formula. Epolactaene is a known compound and is described in JP-A-8-269061.

[0003]

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Epolactaene is a human neuroblast SH-S
Since it produces dendrites peculiar to neuronal differentiation with respect to Y5Y cells, it is useful as an antitumor agent used for treating, for example, neuronal tumors, and a neuronal differentiation inducing agent used for treating and / or preventing neurological diseases and the like. It is believed that.

Up to now, epolactaene is a natural organic compound separated from a culture of a microorganism, and in order to supply it in large quantities and to synthesize analogs, it has been urgently necessary to develop a chemical synthesis method with high flexibility.

Incidentally, for example, J. Org. Chem. 19
1-Acetyl-3,6-dioxabicyclo [3.1.0] hexan-2-one is reported in 93, 58, 62-64, but this compound has a hydrogen atom at the 4-position.
In epolactaene and its derivatives, the substitution at the 4-position is an important factor. Therefore, it is considered that this compound is extremely unlikely to be an intermediate in the synthesis of epolactaene and its derivatives.

[0007]

SUMMARY OF THE INVENTION The present inventors have conducted intensive studies on the synthesis of epolactaene and its derivatives. I found what I could do. Then, they have found that these epoxyethane derivatives are useful for synthesizing epolactaene and its derivatives, and completed the present invention.

That is, the present invention provides an epoxyethane derivative useful as a synthetic intermediate for epolactaene and its derivatives.

[0009]

The present invention provides a compound represented by the general formula:

[0010]

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And a salt thereof.

Here, in the formula, R ¹ is a linear or branched alkyl group having 1 to 6 carbon atoms, and a linear or branched alkyl group having 2 to 12 carbon atoms as a whole. alkoxyalkyl an alkyl group or a linear or branched hydroxyalkyl group having 6 to C 1 -C, R ² represents a hydrogen atom or a protective group for hydroxyl, to R ³ are not substituents [alpha] 1 3 pieces A linear or branched hydrocarbon group having 1 to 15 carbon atoms, which may have 1 to 5 double bonds, and 1 to 6 carbon atoms; linear or branched alkoxy group having a hydroxyl group or formula -N (R ⁵⁾
A group having (R ⁶ ) (provided that R ⁵ is a linear or branched alkyl group having 1 to 6 carbon atoms or a linear or branched alkyl group having 1 to 6 carbon atoms) R ⁶ represents a linear or branched alkyl group having 1 to 6 carbon atoms), and R ⁴ represents a linear or branched alkyl group having 1 to 6 carbon atoms. A branched alkoxy group or a group having the formula —NH (R ⁷ ) (provided that R ⁷ represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms). Or R ² and R ⁴ are bonded together to form a single bond, and the substituent α is hydroxy, formyl,
Straight-chain or branched alkoxycarbonyl or halogen having 2 to 7 carbon atoms;

Here, when R ¹ , R ⁵ , R ⁶ and R ⁷ represent a linear or branched alkyl group having 1 to 6 carbon atoms, the alkyl group may be, for example, methyl, ethyl, Propyl, isopropyl, butyl, isobutyl,
s-butyl, t-butyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-
Dimethylpropyl, 1-ethylpropyl, hexyl, 1
-Methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3 -Dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-
It may be ethylbutyl, 1,1,2-trimethylpropyl or 1,2,2-trimethylpropyl, preferably a linear or branched alkyl group having 1 to 4 carbon atoms, more preferably Is an alkyl group having 1 or 2 carbon atoms, most preferably a methyl group.

When R ¹ is a straight-chain or branched alkoxyalkyl group having 2 to 12 carbon atoms, the alkoxyalkyl group is preferably a straight-chain alkoxyalkyl group having 1 to 6 carbon atoms. Or branched alkyl and linear or branched alkoxy having 1 to 6 carbon atoms. Examples of such an alkoxyalkyl group include methoxymethyl, 2-methoxyethyl, 3-methoxypropyl, 2-methoxypropyl, 2-methoxy-1-methylethyl, 4-methoxybutyl, 3-methoxybutyl, and 3-methoxybutyl -2-methylpropyl, 3-methoxy-1-methylpropyl, 1-methoxymethyl-1-methylethyl, 5-methoxypentyl, 4-methoxy-1-methylbutyl, 4-methoxy-
2-methylbutyl, 4-methoxy-3-methylbutyl,
3-methoxy-1,1-dimethylpropyl, 3-methoxy-1,2-dimethylpropyl, 3-methoxy-2,2
-Dimethylpropyl, 3-methoxy-1-ethylpropyl, 6-methoxyhexyl, 5-methoxy-1-methylpentyl, 5-methoxy-2-methylpentyl, 5-methoxy-3-methylpentyl, 5-methoxy-4 -Methylpentyl, 4-methoxy-1,1-dimethylbutyl,
4-methoxy-1,2-dimethylbutyl, 4-methoxy-1,3-dimethylbutyl, 4-methoxy-2,2-dimethylbutyl, 4-methoxy-2,3-dimethylbutyl, 4-methoxy-3, 3-dimethylbutyl, 4-methoxy-1-ethylbutyl, 4-methoxy-2-ethylbutyl, 3-methoxy-1,1,2-trimethylpropyl, 3-methoxy-1,2,2-trimethylpropyl;
Ethoxymethyl, 2-ethoxyethyl, 3-ethoxypropyl, 2-ethoxypropyl, 2-ethoxy-1-methylethyl, 4-ethoxybutyl, 3-ethoxybutyl, 3-ethoxy-2-methylpropyl, 3-ethoxy- 1-methylpropyl, 1-ethoxymethyl-1-methylethyl, 5-ethoxypentyl, 4-ethoxy-1-
Methylbutyl, 4-ethoxy-2-methylbutyl, 4-
Ethoxy-3-methylbutyl, 3-ethoxy-1,1-
Dimethylpropyl, 3-ethoxy-1, 2-dimethylpropyl, 3-ethoxy-2, 2-dimethylpropyl,
-Ethoxy-1-ethylpropyl, 6-ethoxyhexyl, 5-ethoxy-1-methylpentyl, 5-ethoxy-2-methylpentyl, 5-ethoxy-3-methylpentyl, 5-ethoxy-4-methylpentyl, -Ethoxy-1,1-dimethylbutyl, 4-ethoxy-1,2-
Dimethylbutyl, 4-ethoxy-1,3-dimethylbutyl, 4-ethoxy-2, 2-dimethylbutyl, 4-ethoxy-2, 3-dimethylbutyl, 4-ethoxy-3,3
-Dimethylbutyl, 4-ethoxy-1-ethylbutyl,
4-ethoxy-2-ethylbutyl, 3-ethoxy-1,
1,2-trimethylpropyl, 3-ethoxy-1,2,
2-trimethylpropyl; propoxymethyl, 2-propoxyethyl, 3-propoxypropyl, 2-propoxypropyl, 2-propoxy-1-methylethyl, 4-
Propoxybutyl, 3-propoxybutyl, 3-propoxy-2-methylpropyl, 3-propoxy-1-methylpropyl, 1-propoxymethyl-1-methylethyl, 5-propoxypentyl, 4-propoxy-1-methylbutyl, -Propoxy-2-methylbutyl, 4-
Propoxy-3-methylbutyl, 3-propoxy-1,
1-dimethylpropyl, 3-propoxy-1, 2-dimethylpropyl, 3-propoxy-2, 2-dimethylpropyl, 3-propoxy-1-ethylpropyl, 6-propoxyhexyl, 5-propoxy-1-methylpentyl, 5-propoxy-2-methylpentyl, 5-propoxy-3-methylpentyl, 5-propoxy-4-methylpentyl, 4-propoxy-1, 1-dimethylbutyl, 4-propoxy-1, 2-dimethylbutyl, -Propoxy-1,3-dimethylbutyl, 4-propoxy-
2,2-dimethylbutyl, 4-propoxy-2, 3-dimethylbutyl, 4-propoxy-3, 3-dimethylbutyl, 4-propoxy-1-ethylbutyl, 4-propoxy-2-ethylbutyl, 3-propoxy-1 1,1,2-
Trimethylpropyl, 3-propoxy-1,2,2-trimethylpropyl; butoxymethyl, 2-butoxyethyl, 3-butoxypropyl, 2-butoxypropyl,
-Butoxy-1-methylethyl, 4-butoxybutyl,
3-butoxybutyl, 3-butoxy-2-methylpropyl, 3-butoxy-1-methylpropyl, 1-butoxymethyl-1-methylethyl, 5-butoxypentyl,
-Butoxy-1-methylbutyl, 4-butoxy-2-methylbutyl, 4-butoxy-3-methylbutyl, 3-butoxy-1,1-dimethylpropyl, 3-butoxy-
1,2-dimethylpropyl, 3-butoxy-2, 2-dimethylpropyl, 3-butoxy-1-ethylpropyl,
6-butoxyhexyl, 5-butoxy-1-methylpentyl, 5-butoxy-2-methylpentyl, 5-butoxy-3-methylpentyl, 5-butoxy-4-methylpentyl, 4-butoxy-1,1-dimethyl Butyl, 4-
Butoxy-1,2-dimethylbutyl, 4-butoxy-
1,3-dimethylbutyl, 4-butoxy-2, 2-dimethylbutyl, 4-butoxy-2,3-dimethylbutyl,
4-butoxy-3,3-dimethylbutyl, 4-butoxy-1-ethylbutyl, 4-butoxy-2-ethylbutyl, 3-butoxy-1,1,2-trimethylpropyl,
3-butoxy-1,2,2-trimethylpropyl; pentyloxymethyl, 2-pentyloxyethyl, 3-pentyloxypropyl, 2-pentyloxypropyl,
2-pentyloxy-1-methylethyl, 4-pentyloxybutyl, 3-pentyloxybutyl, 3-pentyloxy-2-methylpropyl, 3-pentyloxy-
1-methylpropyl, 1-pentyloxymethyl-1-
Methylethyl, 5-pentyloxypentyl, 4-pentyloxy-1-methylbutyl, 4-pentyloxy-
2-methylbutyl, 4-pentyloxy-3-methylbutyl, 3-pentyloxy-1, 1-dimethylpropyl, 3-pentyloxy-1, 2-dimethylpropyl,
3-pentyloxy-2,2-dimethylpropyl, 3-
Pentyloxy-1-ethylpropyl, 6-pentyloxyhexyl, 5-pentyloxy-1-methylpentyl, 5-pentyloxy-2-methylpentyl, 5-pentyloxy-3-methylpentyl, 5-pentyloxy-4 -Methylpentyl, 4-pentyloxy-1,1,
-Dimethylbutyl, 4-pentyloxy-1, 2-dimethylbutyl, 4-pentyloxy-1,3-dimethylbutyl, 4-pentyloxy-2,2-dimethylbutyl,
4-pentyloxy-2,3-dimethylbutyl, 4-pentyloxy-3,3-dimethylbutyl, 4-pentyloxy-1-ethylbutyl, 4-pentyloxy-2-
Ethylbutyl, 3-pentyloxy-1,1,2-trimethylpropyl, 3-pentyloxy-1,2,2-trimethylpropyl; hexyloxymethyl, 2-hexyloxyethyl, 3-hexyloxypropyl, 2-hexyloxy Propyl, 2-hexyloxy-1-methylethyl, 4-hexyloxybutyl, 3-hexyloxybutyl, 3-hexyloxy-2-methylpropyl, 3-hexyloxy-1-methylpropyl, 1-hexyloxymethyl- 1-methylethyl, 5-hexyloxypentyl, 4-hexyloxy-1-methylbutyl, 4-hexyloxy-2-methylbutyl, 4-hexyloxy-3-methylbutyl, 3-hexyloxy-
1,1-dimethylpropyl, 3-hexyloxy-1,
2-dimethylpropyl, 3-hexyloxy-2, 2-
Dimethylpropyl, 3-hexyloxy-1-ethylpropyl, 6-hexyloxyhexyl, 5-hexyloxy-1-methylpentyl, 5-hexyloxy-2-
Methylpentyl, 5-hexyloxy-3-methylpentyl, 5-hexyloxy-4-methylpentyl, 4-
Hexyloxy-1,1-dimethylbutyl, 4-hexyloxy-1,2-dimethylbutyl, 4-hexyloxy-1,3-dimethylbutyl, 4-hexyloxy-
2,2-dimethylbutyl, 4-hexyloxy-2,3
-Dimethylbutyl, 4-hexyloxy-3, 3-dimethylbutyl, 4-hexyloxy-1-ethylbutyl,
4-hexyloxy-2-ethylbutyl, 3-hexyloxy-1,1,2-trimethylpropyl, 3-hexyloxy-1,2,2-trimethylpropyl; preferably having 1 to 4 carbon atoms. And an alkoxyalkyl group consisting of a linear or branched alkoxy having 1 to 4 carbon atoms and a linear or branched alkyl having 1 to 4 carbon atoms, more preferably 1 or 2 carbon atoms.
And an alkyl having 1 or 2 carbon atoms.

When R ¹ represents a linear or branched hydroxyalkyl group having 1 to 6 carbon atoms,
The hydroxyalkyl group is, for example, hydroxymethyl, 2
-Hydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 2-hydroxy-1-methylethyl, 4-hydroxybutyl, 3-hydroxybutyl,
-Hydroxy-2-methylpropyl, 3-hydroxy-
1-methylpropyl, 1-hydroxymethyl-1-methylethyl, 5-hydroxypentyl, 4-hydroxy-
1-methylbutyl, 4-hydroxy-2-methylbutyl, 4-hydroxy-3-methylbutyl, 3-hydroxy-1, 1-dimethylpropyl, 3-hydroxy-1,
2-dimethylpropyl, 3-hydroxy-2, 2-dimethylpropyl, 3-hydroxy-1-ethylpropyl,
6-hydroxyhexyl, 5-hydroxy-1-methylpentyl, 5-hydroxy-2-methylpentyl, 5-
Hydroxy-3-methylpentyl, 5-hydroxy-4
-Methylpentyl, 4-hydroxy-1,1-dimethylbutyl, 4-hydroxy-1,2-dimethylbutyl,
-Hydroxy-1,3-dimethylbutyl, 4-hydroxy-2,2-dimethylbutyl, 4-hydroxy-2,3
-Dimethylbutyl, 4-hydroxy-3,3-dimethylbutyl, 4-hydroxy-1-ethylbutyl, 4-hydroxy-2-ethylbutyl, 3-hydroxy-1,1,
2-trimethylpropyl, 3-hydroxy-1, 2, 2
-Preferably a straight-chain or branched hydroxyalkyl group having 1 to 4 carbon atoms, more preferably a hydroxyalkyl group having 1 or 2 carbon atoms. .

When R ² represents a protecting group for a hydroxyl group, the protecting group is not particularly limited as long as it is used as a usual protecting group for a hydroxyl group, and examples thereof include acetyl, propionyl, butyryl, isobutyryl and valeryl. Lower aliphatic acyl groups; aromatic acyl groups such as benzoyl and naphthoyl; aralkyl groups such as benzyl, 4-nitrobenzyl and 4-methoxybenzyl; 2-tetrahydropyranyl, 2-tetrahydrofuranyl and 4-methoxytetrahydropyran Heterocyclic groups such as -4-yl, 2-tetrahydrothiopyranyl; methoxymethyl, ethoxymethyl,
Alkoxyalkyl groups such as 1-methoxyethyl and 1-ethoxyethyl; aralkyloxyalkyl groups such as benzyloxymethyl; alkylthioalkyl groups such as methylthiomethyl; tri (aryl) methyl groups such as trityl; trimethylsilyl, triethyl Cyril,
Tri-lower alkylsilyl groups such as tri-n-propylsilyl and t-butyldimethylsilyl; diphenyl-t-
Diaryl lower alkylsilyl groups such as butylsilyl;

R ³ , R ⁴ and R ⁵ have 1 to 6 carbon atoms
When a straight-chain or branched-chain alkoxy group having two or more is shown, the alkoxy group is, for example, methoxy, ethoxy,
It can be propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, t-butoxy, pentyloxy, isopentyloxy, hexyloxy, isohexyloxy, preferably linear or branched having 1 to 4 carbon atoms. R ³ and R ⁴ are linear or branched alkoxy groups having 3 or 4 carbon atoms, and R ⁵ is preferably 1 or 2 carbon atoms. Is an alkoxy group having

R ³ may have 1 to 3 substituents α, and may further have 1 to 5 double bonds, linear or branched having 1 to 15 carbon atoms. When it is a chain hydrocarbon group (provided that it has at least one double bond, a linear or branched hydrocarbon group having 2 to 15 carbon atoms), it preferably has a substituent α Wherein the substituent is hydroxy, formyl or a linear or branched alkoxycarbonyl having 2 to 5 carbon atoms, and more preferably one substituent α. The substituent may be hydroxy, formyl or alkoxycarbonyl having 2 or 3 carbon atoms.

When the substituent α is a straight-chain or branched alkoxycarbonyl group having 2 to 7 carbon atoms, the alkoxycarbonyl group is, for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
Isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, s-butoxycarbonyl, t-butoxycarbonyl, pentyloxycarbonyl, isopentyloxycarbonyl, hexyloxycarbonyl,
It may be isohexyloxycarbonyl, preferably a linear or branched alkoxycarbonyl group having 2 to 5 carbon atoms, more preferably an alkoxycarbonyl group having 2 or 3 carbon atoms. is there.

When the substituent α represents a halogen atom, the halogen atom may be a fluorine, chlorine, bromine or iodine atom, preferably a chlorine, bromine or iodine atom, most preferably a chlorine atom. Atom or bromine atom.

R ³ may have a substituent α and may further have 1 to 5 double bonds, and may have 1 to 15 carbon atoms. Shows a hydrogen group.

Here, R ³ is an unsubstituted C 1 -C 1
When a straight or branched alkyl group having 5 is shown, examples of the alkyl group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and s.
-Butyl, t-butyl, pentyl, 1-methylbutyl,
2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl , 4-methylpentyl, 1,1-dimethylbutyl,
1,2-dimethylbutyl, 1,3-dimethylbutyl,
2,2-dimethylbutyl, 2,3-dimethylbutyl,
3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,
2-trimethylpropyl, heptyl, octyl, 1-methylheptyl, 2-ethylhexyl, 1,1,3,3-
It may be tetramethylbutyl, nonyl, decyl, undecyl, dodecyl, 1,7-dimethylundecyl, tridecyl, tetradecyl or pentadecyl, preferably straight-chain or branched alkyl having 5 to 14 carbon atoms. And more preferably a linear or branched alkyl group having 10 to 14 carbon atoms.

When R ³ is a straight-chain or branched alkyl group having 1 to 15 carbon atoms having hydroxy as a substituent, examples of the alkyl group include hydroxymethyl, 2-hydroxyethyl, -Hydroxypropyl, 2-hydroxyisopropyl, 4-hydroxybutyl, 3-hydroxyisobutyl, 3-hydroxy-s-butyl, 2-hydroxy-t-butyl, 5-hydroxypentyl, 4-hydroxy-1-methylbutyl, 4- Hydroxy-2-methylbutyl, 4-hydroxy-3-methylbutyl, 3-hydroxy-1,1-dimethylpropyl, 3-hydroxy-1,2-dimethylpropyl, 3-hydroxy-2,2-dimethylpropyl,
-Hydroxy-1-ethylpropyl, 6-hydroxyhexyl, 5-hydroxy-1-methylpentyl, 5-hydroxy-2-methylpentyl, 5-hydroxy-3-
Methylpentyl, 5-hydroxy-4-methylpentyl, 4-hydroxy-1,1-dimethylbutyl, 4-hydroxy-1,2-dimethylbutyl, 4-hydroxy-
1,3-dimethylbutyl, 4-hydroxy-2,2-dimethylbutyl, 4-hydroxy-2,3-dimethylbutyl, 4-hydroxy-3,3-dimethylbutyl, 4-hydroxy-1-ethylbutyl, 4- Hydroxy-2-ethylbutyl, 3-hydroxy-1,1,2-trimethylpropyl, 3-hydroxy-1,2,2-trimethylpropyl, 7-hydroxyheptyl, 8-hydroxyoctyl, 7-hydroxy-1-methylheptyl , 6-hydroxy-2-ethylhexyl, 4-hydroxy-1,
1,3,3-tetramethylbutyl, 9-hydroxynonyl, 10-hydroxydecyl, 11-hydroxyundecyl, 12-hydroxydodecyl, 13-hydroxytridecyl, 11-hydroxy-1,7-dimethylundecyl, 14 -Hydroxytetradecyl or 15-hydroxypentadecyl, preferably a straight-chain or branched hydroxyalkyl group having 5 to 14 carbon atoms, more preferably 5 to 7 carbon atoms. Is a linear or branched hydroxyalkyl group having

When R ³ represents a linear or branched alkyl group having 1 to 15 carbon atoms having formyl as a substituent, examples of the alkyl group include formylmethyl, 2-formylethyl, -Formylpropyl, 2-formylisopropyl, 4-formylbutyl,
3-formyl isobutyl, 3-formyl-s-butyl,
2-formyl-t-butyl, 5-formylpentyl, 4
-Formyl-1-methylbutyl, 4-formyl-2-methylbutyl, 4-formyl-3-methylbutyl, 3-formyl-1,1-dimethylpropyl, 3-formyl-
1,2-dimethylpropyl, 3-formyl-2, 2-dimethylpropyl, 3-formyl-1-ethylpropyl,
6-formylhexyl, 5-formyl-1-methylpentyl, 5-formyl-2-methylpentyl, 5-formyl-3-methylpentyl, 5-formyl-4-methylpentyl, 4-formyl-1,1-dimethyl Butyl, 4-
Formyl-1,2-dimethylbutyl, 4-formyl-
1,3-dimethylbutyl, 4-formyl-2,2-dimethylbutyl, 4-formyl-2,3-dimethylbutyl,
4-formyl-3,3-dimethylbutyl, 4-formyl-1-ethylbutyl, 4-formyl-2-ethylbutyl, 3-formyl-1,1,2-trimethylpropyl,
3-formyl-1,2,2-trimethylpropyl, 7-
Formylheptyl, 8-formyloctyl, 7-formyl-1-methylheptyl, 6-formyl-2-ethylhexyl, 4-formyl-1,1,3,3-tetramethylbutyl, 9-formylnonyl, 10-formyldecyl,
11-formylundecyl, 12-formyldodecyl,
13-formyltridecyl, 11-formyl-1,7-
Dimethylundecyl, 14-formyltetradecyl or 15-formylpentadecyl, preferably a linear or branched alkyl group having 4 to 13 carbon atoms having formyl as a substituent; More preferably, it has 4 to 6 carbon atoms having formyl as a substituent.
A linear or branched alkyl group having a single bond.

R ³ is a straight-chain or branched-chain alkyl group having 1 to 15 carbon atoms having a straight-chain or branched-chain alkoxycarbonyl having 2 to 7 carbon atoms as a substituent. When indicated, the alkyl group includes, for example, methoxycarbonylmethyl, 2-methoxycarbonylethyl, 3-methoxycarbonylpropyl,
-Methoxycarbonylisopropyl, 4-methoxycarbonylbutyl, 3-methoxycarbonylisobutyl, 3
-Methoxycarbonyl-s-butyl, 2-methoxycarbonyl-t-butyl, 5-methoxycarbonylpentyl, 4-methoxycarbonyl-1-methylbutyl, 4-
Methoxycarbonyl-2-methylbutyl, 4-methoxycarbonyl-3-methylbutyl, 3-methoxycarbonyl-1, 1-dimethylpropyl, 3-methoxycarbonyl-1, 2-dimethylpropyl, 3-methoxycarbonyl-2, 2-dimethyl Propyl, 3-methoxycarbonyl-1-ethylpropyl, 6-methoxycarbonylhexyl, 5-methoxycarbonyl-1-methylpentyl,
5-methoxycarbonyl-2-methylpentyl, 5-methoxycarbonyl-3-methylpentyl, 5-methoxycarbonyl-4-methylpentyl, 4-methoxycarbonyl-1, 1-dimethylbutyl, 4-methoxycarbonyl-1,2 -Dimethylbutyl, 4-methoxycarbonyl-1,3-dimethylbutyl, 4-methoxycarbonyl-
2,2-dimethylbutyl, 4-methoxycarbonyl-
2,3-dimethylbutyl, 4-methoxycarbonyl-
3,3-dimethylbutyl, 4-methoxycarbonyl-1
-Ethylbutyl, 4-methoxycarbonyl-2-ethylbutyl, 3-methoxycarbonyl-1,1,2-trimethylpropyl, 3-methoxycarbonyl-1,2,2-
Trimethylpropyl, 7-methoxycarbonylheptyl, 8-methoxycarbonyloctyl, 7-methoxycarbonyl-1-methylheptyl, 6-methoxycarbonyl-2-ethylhexyl, 4-methoxycarbonyl-
1,1,3,3-tetramethylbutyl, 9-methoxycarbonylnonyl, 10-methoxycarbonyldecyl,
1-methoxycarbonylundecyl, 12-methoxycarbonyldodecyl, 13-methoxycarbonyltridecyl, 11-methoxycarbonyl-1,7-dimethylundecyl, 14-methoxycarbonyltetradecyl, 15
-Methoxycarbonylpentadecyl; ethoxycarbonylmethyl, 2-ethoxycarbonylethyl, 3-ethoxycarbonylpropyl, 2-ethoxycarbonylisopropyl, 4-ethoxycarbonylbutyl, 3-ethoxycarbonylisobutyl, 3-ethoxycarbonyl-s-
Butyl, 2-ethoxycarbonyl-t-butyl, 5-ethoxycarbonylpentyl, 4-ethoxycarbonyl-
1-methylbutyl, 4-ethoxycarbonyl-2-methylbutyl, 4-ethoxycarbonyl-3-methylbutyl, 3-ethoxycarbonyl-1, 1-dimethylpropyl, 3-ethoxycarbonyl-1, 2-dimethylpropyl, 3-ethoxycarbonyl -2,2-dimethylpropyl, 3-ethoxycarbonyl-1-ethylpropyl, 6
-Ethoxycarbonylhexyl, 5-ethoxycarbonyl-1-methylpentyl, 5-ethoxycarbonyl-2
-Methylpentyl, 5-ethoxycarbonyl-3-methylpentyl, 5-ethoxycarbonyl-4-methylpentyl, 4-ethoxycarbonyl-1,1-dimethylbutyl, 4-ethoxycarbonyl-1,2-dimethylbutyl, 4- Ethoxycarbonyl-1,3-dimethylbutyl, 4-ethoxycarbonyl-2,2-dimethylbutyl, 4-ethoxycarbonyl-2,3-dimethylbutyl, 4-ethoxycarbonyl-3,3-dimethylbutyl, 4-ethoxycarbonyl -1-ethylbutyl, 4-
Ethoxycarbonyl-2-ethylbutyl, 3-ethoxycarbonyl-1,1,2-trimethylpropyl, 3-ethoxycarbonyl-1,2,2-trimethylpropyl,
7-ethoxycarbonylheptyl, 8-ethoxycarbonyloctyl, 7-ethoxycarbonyl-1-methylheptyl, 6-ethoxycarbonyl-2-ethylhexyl, 4-ethoxycarbonyl-1,1,3,3-tetramethylbutyl, 9- Ethoxycarbonylnonyl, 10-
Ethoxycarbonyldecyl, 11-ethoxycarbonylundecyl, 12-ethoxycarbonyldodecyl, 13
-Ethoxycarbonyltridecyl, 11-ethoxycarbonyl-1,7-dimethylundecyl, 14-ethoxycarbonyltetradecyl, 15-ethoxycarbonylpentadecyl; propoxycarbonylmethyl, 2-propoxycarbonylethyl, 3-propoxycarbonylpropyl, 2 -Propoxycarbonylisopropyl, 4-propoxycarbonylbutyl, 3-propoxycarbonylisobutyl, 5-propoxycarbonylpentyl, 4-
Propoxycarbonyl-1-methylbutyl, 6-propoxycarbonylhexyl, 5-propoxycarbonyl-
1-methylpentyl, 7-propoxycarbonylheptyl, 8-propoxycarbonyloctyl, 7-propoxycarbonyl-1-methylheptyl, 9-propoxycarbonylnonyl, 10-propoxycarbonyldecyl,
11-propoxycarbonylundecyl, 12-propoxycarbonyldodecyl, 13-propoxycarbonyltridecyl, 11-propoxycarbonyl-1,7-dimethylundecyl, 14-propoxycarbonyltetradecyl or 15-propoxycarbonylpentadecyl; butoxycarbonylmethyl , 2-butoxycarbonylethyl, 3-butoxycarbonylpropyl, 2-butoxycarbonylisopropyl, 4-butoxycarbonylbutyl, 3-butoxycarbonylisobutyl, 5-butoxycarbonylpentyl, 4-butoxycarbonyl-
1-methylbutyl, 6-butoxycarbonylhexyl,
5-butoxycarbonyl-1-methylpentyl, 7-butoxycarbonylheptyl, 8-butoxycarbonyloctyl, 7-butoxycarbonyl-1-methylheptyl, 9-butoxycarbonylnonyl, 10-butoxycarbonyldecyl, 11-butoxycarbonylundecyl , 12-butoxycarbonyldodecyl, 13-butoxycarbonyltridecyl, 11-butoxycarbonyl-
1,7-dimethylundecyl, 14-butoxycarbonyltetradecyl, 15-butoxycarbonylpentadecyl; pentyloxycarbonylmethyl, 2-pentyloxycarbonylethyl, 3-pentyloxycarbonylpropyl, 2-pentyloxycarbonylisopropyl, 4- Pentyloxycarbonylbutyl, 3-pentyloxycarbonylisobutyl, 5-pentyloxycarbonylpentyl, 4-pentyloxycarbonyl-1
-Methylbutyl, 6-pentyloxycarbonylhexyl, 5-pentyloxycarbonyl-1-methylpentyl, 7-pentyloxycarbonylheptyl, 8-pentyloxycarbonyloctyl, 7-pentyloxycarbonyl-1-methylheptyl, 9-pentyloxy Carbonyl nonyl, 10-pentyloxycarbonyldecyl, 11-pentyloxycarbonylundecyl, 12
-Pentyloxycarbonyldodecyl, 13-pentyloxycarbonyltridecyl, 11-pentyloxycarbonyl-1,7-dimethylundecyl, 14-pentyloxycarbonyltetradecyl, 15-pentyloxycarbonylpentadecyl; hexyloxycarbonylmethyl, -Hexyloxycarbonylethyl, 3-hexyloxycarbonylpropyl, 2-hexyloxycarbonylisopropyl, 4-hexyloxycarbonylbutyl, 3-hexyloxycarbonylisobutyl,
5-hexyloxycarbonylhexyl, 4-hexyloxycarbonyl-1-methylbutyl, 6-hexyloxycarbonylhexyl, 5-hexyloxycarbonyl-1-methylhexyl, 7-hexyloxycarbonylheptyl, 8-hexyloxycarbonyloctyl,
7-hexyloxycarbonyl-1-methylheptyl,
9-hexyloxycarbonylnonyl, 10-hexyloxycarbonyldecyl, 11-hexyloxycarbonylundecyl, 12-hexyloxycarbonyldodecyl, 13-hexyloxycarbonyltridecyl, 1
1-hexyloxycarbonyl-1,7-dimethylundecyl, 14-hexyloxycarbonyltetradecyl, 15-hexyloxycarbonylpentadecyl; preferably a straight-chain having 2 to 5 carbon atoms as a substituent. A linear or branched alkyl group having 5 to 14 carbon atoms having a linear or branched alkoxycarbonyl, and more preferably a linear or branched alkyl group having 2 or 3 carbon atoms as a substituent. A straight-chain or branched alkyl group having 5 to 7 carbon atoms having a linear or branched alkoxycarbonyl group.

When R ³ represents a straight-chain or branched-chain alkyl group having 1 to 15 carbon atoms having halogen as a substituent, examples of the alkyl group include fluoromethyl, 2-fluoroethyl and 3-alkyl. -Fluoropropyl, 2-fluoroisopropyl, 4-fluorobutyl,
3-fluoroisobutyl, 3-fluoro-s-butyl,
2-fluoro-t-butyl, 5-fluoropentyl, 4
-Fluoro-1-methylbutyl, 4-fluoro-2-methylbutyl, 4-fluoro-3-methylbutyl, 3-fluoro-1,1-dimethylpropyl, 3-fluoro-
1,2-dimethylpropyl, 3-fluoro-2, 2-dimethylpropyl, 3-fluoro-1-ethylpropyl,
6-fluorohexyl, 5-fluoro-1-methylpentyl, 5-fluoro-2-methylpentyl, 5-fluoro-3-methylpentyl, 5-fluoro-4-methylpentyl, 4-fluoro-1,1-dimethyl Butyl, 4-
Fluoro-1,2-dimethylbutyl, 4-fluoro-
1,3-dimethylbutyl, 4-fluoro-2,2-dimethylbutyl, 4-fluoro-2,3-dimethylbutyl,
4-fluoro-3,3-dimethylbutyl, 4-fluoro-1-ethylbutyl, 4-fluoro-2-ethylbutyl, 3-fluoro-1,1,2-trimethylpropyl,
3-fluoro-1,2,2-trimethylpropyl, 7-
Fluoroheptyl, 8-fluorooctyl, 7-fluoro-1-methylheptyl, 6-fluoro-2-ethylhexyl, 4-fluoro-1,1,3,3-tetramethylbutyl, 9-fluorononyl, 10-fluorodecyl ,
11-fluoroundecyl, 12-fluorododecyl,
13-fluorotridecyl, 11-fluoro-1,7-
Dimethylundecyl, 14-fluorotetradecyl, 1
5-fluoropentadecyl; chloromethyl, 2-chloroethyl, 3-chloropropyl, 2-chloroisopropyl, 4-chlorobutyl, 3-chloroisobutyl, 3-chloro-s-butyl, 2-chloro-t-butyl, 5-chloropentadecyl; Chloropentyl, 4-chloro-1-methylbutyl, 4-chloro-2-methylbutyl, 4-chloro-3-methylbutyl, 3-chloro-1,1-dimethylpropyl, 3-chloro-1,2-dimethylpropyl, -Chloro-2,2-
Dimethylpropyl, 3-chloro-1-ethylpropyl,
6-chlorohexyl, 5-chloro-1-methylpentyl, 5-chloro-2-methylpentyl, 5-chloro-3
-Methylpentyl, 5-chloro-4-methylpentyl,
4-chloro-1,1-dimethylbutyl, 4-chloro-
1,2-dimethylbutyl, 4-chloro-1,3-dimethylbutyl, 4-chloro-2,2-dimethylbutyl, 4-
Chloro-2,3-dimethylbutyl, 4-chloro-3,3
-Dimethylbutyl, 4-chloro-1-ethylbutyl, 4
-Chloro-2-ethylbutyl, 3-chloro-1,1,2
-Trimethylpropyl, 3-chloro-1,2,2-trimethylpropyl, 7-chloroheptyl, 8-chlorooctyl, 7-chloro-1-methylheptyl, 6-chloro-
2-ethylhexyl, 4-chloro-1,1,3,3-tetramethylbutyl, 9-chlorononyl, 10-chlorodecyl, 11-chloroundecyl, 12-chlorododecyl, 13-chlorotridecyl, 11-chloro-1 , 7-
Dimethylundecyl, 14-chlorotetradecyl, 15
-Chloropentadecyl; bromomethyl, 2-bromoethyl, 3-bromopropyl, 2-bromoisopropyl,
-Bromobutyl, 3-bromoisobutyl, 5-bromopentyl, 4-bromo-1-methylbutyl, 6-bromohexyl, 5-bromo-1-methylpentyl, 7-bromoheptyl, 8-bromooctyl, 7-bromo-1 -Methylheptyl, 9-bromononyl, 10-bromodecyl,
11-bromoundecyl, 12-bromododecyl, 13
-Bromotridecyl, 11-bromo-1,7-dimethylundecyl, 14-bromotetradecyl, 15-bromopentadecyl; iodomethyl, 2-iodoethyl, 3-
Iodopropyl, 2-iodoisopropyl, 4-iodobutyl, 3-iodoisobutyl, 5-iodopentyl,
4-iodo-1-methylbutyl, 6-iodohexyl,
5-iodo-1-methylpentyl, 7-iodoheptyl, 8-iodooctyl, 7-iodo-1-methylheptyl, 9-iodononyl, 10-iododecyl, 11-
Iodoundecyl, 12-iodododecyl, 13-iodotridecyl, 11-iodo-1,7-dimethylundecyl, 14-iodotetradecyl, 15-iodopentadecyl; preferably chloro as a substituent. A straight-chain or branched alkyl group having 5 to 14 carbon atoms having bromo or iodo, and more preferably having 5 carbon atoms having chloro or bromo as a substituent.
A linear or branched alkyl group having from 7 to 7;

When R ³ represents a linear or branched hydrocarbon group having 1 to 5 unsubstituted double bonds and 2 to 15 carbon atoms, the hydrocarbon group includes:
For example, vinyl, 1-methylvinyl, 1-propenyl, 2
-Propenyl, 1-methylvinyl, 1-butenyl, 2-
Butenyl, 2-methyl-2-propenyl, 1,3-butadienyl, 1-pentenyl, 2-pentenyl, 1-methyl-1-butenyl, 1-hexenyl, 2-hexenyl, 1-methyl-1-pentenyl, 1 , 4-hexadienyl, 1-heptenyl, 1,6-heptadienyl, 1,
3,6-heptatrienyl, 1-octenyl, 1-butyl-2-butenyl, 4-propyl-2-pentenyl,
3,5-dimethyl-1-hexenyl, 1-nonenyl, 1
-Decenyl, 1-undecenyl, 1-dodecenyl, 1,
7-dimethyl-1,5,7,9-undecatetraenyl, 1-tridecenyl, 1-tetradecenyl or 1-
It may be pentadecenyl, preferably a straight-chain or branched hydrocarbon group having 1 to 4 double bonds and 5 to 14 carbon atoms, and more preferably a double-bonded hydrocarbon group. It is a linear or branched hydrocarbon group having 1 or 2 carbon atoms and 5 to 7 carbon atoms.

When R ³ represents a straight-chain or branched hydrocarbon group having hydroxy as a substituent, having 1 to 5 double bonds, and having 2 to 15 carbon atoms,
Examples of the hydrocarbon group include 2-hydroxyvinyl,
2-hydroxy-1-methylvinyl, 3-hydroxy-
1-propenyl, 3-hydroxy-2-propenyl, 4
-Hydroxy-1-butenyl, 4-hydroxy-2-butenyl, 3-hydroxy-2-methyl-2-propenyl, 4-hydroxy-1,3-butadienyl, 5-hydroxy-1-pentenyl, 5-hydroxy-2 -Pentenyl, 4-hydroxy-1-methyl-1-butenyl, 6
-Hydroxy-1-hexenyl, 6-hydroxy-2-
Hexenyl, 5-hydroxy-1-methyl-1-pentenyl, 6-hydroxy-1,4-hexadienyl, 7-
Hydroxy-1-heptenyl, 7-hydroxy-1,6
-Heptadienyl, 7-hydroxy-1,3,6-heptatrienyl, 8-hydroxy-1-octenyl, 4-
Hydroxy-1-butyl-2-butenyl, 5-hydroxy-4-propyl-2-pentenyl, 6-hydroxy-
3,5-dimethyl-1-hexenyl, 9-hydroxy-
1-nonenyl, 10-hydroxy-1-decenyl, 11
-Hydroxy-1-undecenyl, 12-hydroxy-
1-dodecenyl, 11-hydroxy-1,7-dimethyl-1,5,7,9-undecatetraenyl, 13-hydroxy-1-tridecenyl, 14-hydroxy-1-tetradecenyl or 15-hydroxy-1-pentadecenyl Which preferably has hydroxy as a substituent, has 1 to 4 double bonds, and has 5 to 14 carbon atoms.
And more preferably a straight-chain or branched-chain hydrocarbon group having hydroxy as a substituent, having one or two double bonds, and having 5 to 7 carbon atoms. It is a chain or branched hydrocarbon group.

When R ³ represents a straight-chain or branched hydrocarbon group having formyl as a substituent, having 1 to 5 double bonds, and having 2 to 15 carbon atoms, Examples of the hydrocarbon group include 2-formylvinyl and 2-
Formyl-1-methylvinyl, 3-formyl-1-propenyl, 3-formyl-2-propenyl, 4-formyl-1-butenyl, 4-formyl-2-butenyl, 3-formyl-2-methyl-2-propenyl , 4-formyl-
1,3-butadienyl, 5-formyl-1-pentenyl, 5-formyl-2-pentenyl, 4-formyl-1
-Methyl-1-butenyl, 6-formyl-1-hexenyl, 6-formyl-2-hexenyl, 5-formyl-1
-Methyl-1-pentenyl, 6-formyl-1,4-hexadienyl, 7-formyl-1-heptenyl, 7-formyl-1,6-heptadienyl, 7-formyl-1,
3,6-heptatrienyl, 8-formyl-1-octenyl, 4-formyl-1-butyl-2-butenyl, 5-
Formyl-4-propyl-2-pentenyl, 6-formyl-3,5-dimethyl-1-hexenyl, 9-formyl-1-nonenyl, 10-formyl-1-decenyl, 11
-Formyl-1-undecenyl, 12-formyl-1-
Dodecenyl, 11-formyl-1,7-dimethyl-1,
5,7,9-undecatetraenyl, 13-formyl-
It may be 1-tridecenyl, 14-formyl-1-tetradecenyl or 15-formyl-1-pentadecenyl, preferably having formyl as a substituent, having 1 to 4 double bonds, and having 4 to 13 carbon atoms. A linear or branched formyl hydrocarbon group having 1 or 2 carbon atoms, more preferably having formyl as a substituent, having 1 or 2 double bonds, and having 4 to 6 carbon atoms. A linear or branched hydrocarbon group.

R ³ has a substituted or unsubstituted linear or branched alkoxycarbonyl having 2 to 7 carbon atoms, has 1 to 5 double bonds, and has 2 to 15 carbon atoms. When it represents a linear or branched hydrocarbon group, the hydrocarbon group includes, for example, 2-methoxycarbonylvinyl, 2-methoxycarbonyl-1-methylvinyl, 3-methoxycarbonyl-1-propenyl,
3-methoxycarbonyl-2-propenyl, 4-methoxycarbonyl-1-butenyl, 4-methoxycarbonyl-2-butenyl, 3-methoxycarbonyl-2-methyl-2-propenyl, 4-methoxycarbonyl-1,3-
Butadienyl, 5-methoxycarbonyl-1-pentenyl, 5-methoxycarbonyl-2-pentenyl, 4-methoxycarbonyl-1-methyl-1-butenyl, 6-methoxycarbonyl-1-hexenyl, 6-methoxycarbonyl-2-hexenyl , 5-methoxycarbonyl-1
-Methyl-1-pentenyl, 6-methoxycarbonyl-
1,4-hexadienyl, 7-methoxycarbonyl-1
-Heptenyl, 7-methoxycarbonyl-1,6-heptadienyl, 7-methoxycarbonyl-1,3,6-heptatrienyl, 8-methoxycarbonyl-1-octenyl, 4-methoxycarbonyl-1-butyl-2-butenyl, 5 -Methoxycarbonyl-4-propyl-2-pentenyl, 6-methoxycarbonyl-3,5-dimethyl-1-hexenyl, 9-methoxycarbonyl-1-nonenyl, 10-methoxycarbonyl-1-decenyl, 11
-Methoxycarbonyl-1-undecenyl, 12-methoxycarbonyl-1-dodecenyl, 9-methoxycarbonyl-1,7-dimethylundeca-1,5,7,9-tetraenyl, 11-methoxycarbonyl-1,7-dimethyl Undeca-1,5,7,9-tetraenyl, 13-
Methoxycarbonyl-1-tridecenyl, 14-methoxycarbonyl-1-tetradecenyl, 15-methoxycarbonyl-1-pentadecenyl; 2-ethoxycarbonylvinyl, 2-ethoxycarbonyl-1-methylvinyl, 3-ethoxycarbonyl-1-propenyl, 3-ethoxycarbonyl-2-propenyl, 4-ethoxycarbonyl-1-butenyl, 4-ethoxycarbonyl-2-
Butenyl, 3-ethoxycarbonyl-2-methyl-2-
Propenyl, 4-ethoxycarbonyl-1,3-butadienyl, 5-ethoxycarbonyl-1-pentenyl, 5
-Ethoxycarbonyl-2-pentenyl, 4-ethoxycarbonyl-1-methyl-1-butenyl, 6-ethoxycarbonyl-1-hexenyl, 6-ethoxycarbonyl-2-hexenyl, 5-ethoxycarbonyl-1-methyl-1-methyl Pentenyl, 6-ethoxycarbonyl-1,4
-Hexadienyl, 7-ethoxycarbonyl-1-heptenyl, 7-ethoxycarbonyl-1,6-heptadienyl, 7-ethoxycarbonyl-1,3,6-heptatrienyl, 8-ethoxycarbonyl-1-octenyl,
4-ethoxycarbonyl-1-butyl-2-butenyl,
5-ethoxycarbonyl-4-propyl-2-pentenyl, 6-ethoxycarbonyl-3,5-dimethyl-1-
Hexenyl, 9-ethoxycarbonyl-1-nonenyl,
10-ethoxycarbonyl-1-decenyl, 11-ethoxycarbonyl-1-undecenyl, 12-ethoxycarbonyl-1-dodecenyl, 9-ethoxycarbonyl-
1,7-dimethylundeca-1,5,7,9-tetraenyl, 11-ethoxycarbonyl-1,7-dimethylundeca-1,5,7,9-tetraenyl, 13-ethoxycarbonyl-1-tridecenyl, 14-ethoxycarbonyl-1-tetradecenyl, 15-ethoxycarbonyl-1-pentadecenyl; 2-propoxycarbonylvinyl, 2-propoxycarbonyl-1-methylvinyl, 3-propoxycarbonyl-1-propenyl, 3-
Propoxycarbonyl-2-propenyl, 4-propoxycarbonyl-1-butenyl, 4-propoxycarbonyl-2-butenyl, 3-propoxycarbonyl-2-methyl-2-propenyl, 4-propoxycarbonyl-
1,3-butadienyl, 5-propoxycarbonyl-1
-Pentenyl, 5-propoxycarbonyl-2-pentenyl, 4-propoxycarbonyl-1-methyl-1-butenyl, 6-propoxycarbonyl-1-hexenyl,
6-propoxycarbonyl-2-hexenyl, 5-propoxycarbonyl-1-methyl-1-pentenyl, 6-
Propoxycarbonyl-1,4-hexadienyl, 7-
Propoxycarbonyl-1-heptenyl, 7-propoxycarbonyl-1,6-heptadienyl, 7-propoxycarbonyl-1,3,6-heptatrienyl, 8-propoxycarbonyl-1-octenyl, 4-propoxycarbonyl-1-butyl-2 -Butenyl, 5-propoxycarbonyl-4-propyl-2-pentenyl, 6-propoxycarbonyl-3,5-dimethyl-1-hexenyl, 9-propoxycarbonyl-1-nonenyl, 10-
Propoxycarbonyl-1-decenyl, 11-propoxycarbonyl-1-undecenyl, 12-propoxycarbonyl-1-dodecenyl, 9-propoxycarbonyl-1,7-dimethylundeca-1,5,7,9-tetraenyl, 11- 2-propoxycarbonyl-1,7-dimethylundeca-1,5,7,9-tetraenyl, 13-propoxycarbonyl-1-tridecenyl, 14-propoxycarbonyl-1-tetradecenyl, 15-propoxycarbonyl-1-pentadecenyl; 2- Butoxycarbonylvinyl, 2-butoxycarbonyl-1-methylvinyl, 3-butoxycarbonyl-1-propenyl, 3-
Butoxycarbonyl-2-propenyl, 4-butoxycarbonyl-1-butenyl, 4-butoxycarbonyl-2
-Butenyl, 3-butoxycarbonyl-2-methyl-2
-Propenyl, 4-butoxycarbonyl-1,3-butadienyl, 5-butoxycarbonyl-1-pentenyl,
5-butoxycarbonyl-2-pentenyl, 4-butoxycarbonyl-1-methyl-1-butenyl, 6-butoxycarbonyl-1-hexenyl, 6-butoxycarbonyl-2-hexenyl, 5-butoxycarbonyl-1-methyl-1 -Pentenyl, 6-butoxycarbonyl-1,
4-hexadienyl, 7-butoxycarbonyl-1-heptenyl, 7-butoxycarbonyl-1,6-heptadienyl, 7-butoxycarbonyl-1,3,6-heptatrienyl, 8-butoxycarbonyl-1-octenyl, 4-butoxycarbonyl -1-butyl-2-butenyl, 5-butoxycarbonyl-4-propyl-2-pentenyl, 6-butoxycarbonyl-3,5-dimethyl-
1-hexenyl, 9-butoxycarbonyl-1-nonenyl, 10-butoxycarbonyl-1-decenyl, 11-
Butoxycarbonyl-1-undecenyl, 12-butoxycarbonyl-1-dodecenyl, 9-butoxycarbonyl-1,7-dimethylundeca-1,5,7,9-tetraenyl, 11-butoxycarbonyl-1,7-dimethylun Deca-1,5,7,9-tetraenyl, 13-butoxycarbonyl-1-tridecenyl, 14-butoxycarbonyl-1-tetradecenyl, 15-butoxycarbonyl-1-pentadecenyl; 2-pentyloxycarbonylvinyl, 2-pentyloxy Carbonyl-1-methylvinyl, 3-pentyloxycarbonyl-1-propenyl, 3-pentyloxycarbonyl-2-propenyl, 4-pentyloxycarbonyl-1-butenyl,
-Pentyloxycarbonyl-2-butenyl, 3-pentyloxycarbonyl-2-methyl-2-propenyl,
4-pentyloxycarbonyl-1,3-butadienyl, 5-pentyloxycarbonyl-1-pentenyl,
5-pentyloxycarbonyl-2-pentenyl, 4-
Pentyloxycarbonyl-1-methyl-1-butenyl, 6-pentyloxycarbonyl-1-hexenyl,
6-pentyloxycarbonyl-2-hexenyl, 5-
Pentyloxycarbonyl-1-methyl-1-pentenyl, 6-pentyloxycarbonyl-1,4-hexadienyl, 7-pentyloxycarbonyl-1-heptenyl, 7-pentyloxycarbonyl-1,6-heptadienyl, 7-pentyloxy Carbonyl-1,3,6-
Heptatrienyl, 8-pentyloxycarbonyl-1
-Octenyl, 4-pentyloxycarbonyl-1-butyl-2-butenyl, 5-pentyloxycarbonyl-
4-propyl-2-pentenyl, 6-pentyloxycarbonyl-3,5-dimethyl-1-hexenyl, 9-pentyloxycarbonyl-1-nonenyl, 10-pentyloxycarbonyl-1-decenyl, 11-pentyloxycarbonyl- 1-undecenyl, 12-pentyloxycarbonyl-1-dodecenyl, 9-pentyloxycarbonyl-1,7-dimethylundeca-1,5,7,
9-tetraenyl, 11-pentyloxycarbonyl-
1,7-dimethylundeca-1,5,7,9-tetraenyl, 13-pentyloxycarbonyl-1-tridecenyl, 14-pentyloxycarbonyl-1-tetradecenyl, 15-pentyloxycarbonyl-1-pentadecenyl; 2- Hexyloxycarbonylvinyl, 2-
Hexyloxycarbonyl-1-methylvinyl, 3-hexyloxycarbonyl-1-propenyl, 3-hexyloxycarbonyl-2-propenyl, 4-hexyloxycarbonyl-1-butenyl, 4-hexyloxycarbonyl-2-butenyl, 3 -Hexyloxycarbonyl-2-methyl-2-propenyl, 4-hexyloxycarbonyl-1,3-butadienyl, 5-hexyloxycarbonyl-1-pentenyl, 5-hexyloxycarbonyl-2-pentenyl, 4-hexyloxycarbonyl -1-methyl-1-butenyl, 6-hexyloxycarbonyl-1-hexenyl, 6-hexyloxycarbonyl-2-hexenyl, 5-hexyloxycarbonyl-1-methyl-1-pentenyl, 6-hexyloxycarbonyl-1 , - hexadienyl, 7-hexyloxycarbonyl-1-heptenyl, 7-hexyloxycarbonyl-1,6-heptadienyl, 7- hexyloxycarbonyl 1,3,6 heptatrienyl, 8-
Hexyloxycarbonyl-1-octenyl, 4-hexyloxycarbonyl-1-butyl-2-butenyl, 5
-Hexyloxycarbonyl-4-propyl-2-pentenyl, 6-hexyloxycarbonyl-3,5-dimethyl-1-hexenyl, 9-hexyloxycarbonyl-1-nonenyl, 10-hexyloxycarbonyl-1
-Decenyl, 11-hexyloxycarbonyl-1-undecenyl, 12-hexyloxycarbonyl-1-dodecenyl, 9-hexyloxycarbonyl-1,7-dimethylundeca-1,5,7,9-tetraenyl, 11
-Hexyloxycarbonyl-1,7-dimethylundeca-1,5,7,9-tetraenyl, 13-hexyloxycarbonyl-1-tridecenyl, 14-hexyloxycarbonyl-1-tetradecenyl or 15-hexyloxycarbonyl-1 -Pentadecenyl; preferably having a straight-chain or branched alkoxycarbonyl having 2 to 5 carbon atoms as a substituent, having 1 to 4 double bonds, and having 5 carbon atoms. Or 14
A linear or branched hydrocarbon group having 2 or 3 carbon atoms, more preferably a straight or branched alkoxycarbonyl group having 2 or 3 carbon atoms, and having 3 double bonds. Or a linear or branched hydrocarbon group having 4 and 12 to 14 carbon atoms.

When R ³ represents a straight-chain or branched-chain hydrocarbon group having 1 to 5 double bonds and 2 to 15 carbon atoms and having halogen as a substituent, said hydrocarbon As the group, for example, 2-fluorovinyl, 2-
Fluoro-1-methylvinyl, 3-fluoro-1-propenyl, 3-fluoro-2-propenyl, 4-fluoro-1-butenyl, 4-fluoro-2-butenyl, 3-fluoro-2-methyl-2-propenyl , 4-fluoro-
1,3-butadienyl, 5-fluoro-1-pentenyl, 5-fluoro-2-pentenyl, 4-fluoro-1
-Methyl-1-butenyl, 6-fluoro-1-hexenyl, 6-fluoro-2-hexenyl, 5-fluoro-1
-Methyl-1-pentenyl, 6-fluoro-1,4-hexadienyl, 7-fluoro-1-heptenyl, 7-fluoro-1,6-heptadienyl, 7-fluoro-1,
3,6-heptatrienyl, 8-fluoro-1-octenyl, 4-fluoro-1-butyl-2-butenyl, 5-
Fluoro-4-propyl-2-pentenyl, 6-fluoro-3,5-dimethyl-1-hexenyl, 9-fluoro-1-nonenyl, 10-fluoro-1-decenyl, 11
-Fluoro-1-undecenyl, 12-fluoro-1-
Dodecenyl, 11-fluoro-1,7-dimethyl-1,
5,7,9-undecatetraenyl, 13-fluoro-
1-tridecenyl, 14-fluoro-1-tetradecenyl, 15-fluoro-1-pentadecenyl; 2-chlorovinyl, 2-chloro-1-methylvinyl, 3-chloro-
1-propenyl, 3-chloro-2-propenyl, 4-chloro-1-butenyl, 4-chloro-2-butenyl, 3-
Chloro-2-methyl-2-propenyl, 4-chloro-
1,3-butadienyl, 5-chloro-1-pentenyl,
5-chloro-2-pentenyl, 4-chloro-1-methyl-1-butenyl, 6-chloro-1-hexenyl, 6-chloro-2-hexenyl, 5-chloro-1-methyl-1-
Pentenyl, 6-chloro-1,4-hexadienyl, 7
-Chloro-1-heptenyl, 7-chloro-1,6-heptadienyl, 7-chloro-1,3,6-heptatrienyl, 8-chloro-1-octenyl, 4-chloro-1-butyl-2-butenyl, 5 -Chloro-4-propyl-2-
Pentenyl, 6-chloro-3,5-dimethyl-1-hexenyl, 9-chloro-1-nonenyl, 10-chloro-1
-Decenyl, 11-chloro-1-undecenyl, 12-
Chloro-1-dodecenyl, 11-chloro-1,7-dimethyl-1,5,7,9-undecatetraenyl, 13-
Chloro-1-tridecenyl, 14-chloro-1-tetradecenyl, 15-chloro-1-pentadecenyl; 2-bromovinyl, 2-bromo-1-methylvinyl, 3-bromo-1-propenyl, 3-bromo-2-propenyl , 4
-Bromo-1-butenyl, 4-bromo-2-butenyl,
3-bromo-2-methyl-2-propenyl, 4-bromo-1,3-butadienyl, 5-bromo-1-pentenyl, 5-bromo-2-pentenyl, 4-bromo-1-methyl-1-butenyl, 6-bromo-1-hexenyl, 6
-Bromo-2-hexenyl, 5-bromo-1-methyl-
1-pentenyl, 6-bromo-1,4-hexadienyl, 7-bromo-1-heptenyl, 7-bromo-1,6
-Heptadienyl, 7-bromo-1,3,6-heptatrienyl, 8-bromo-1-octenyl, 4-bromo-
1-butyl-2-butenyl, 5-bromo-4-propyl-2-pentenyl, 6-bromo-3,5-dimethyl-1
-Hexenyl, 9-bromo-1-nonenyl, 10-bromo-1-decenyl, 11-bromo-1-undecenyl,
12-bromo-1-dodecenyl, 11-bromo-1,7
-Dimethyl-1,5,7,9-undecatetraenyl,
13-bromo-1-tridecenyl, 14-bromo-1-
Tetradecenyl, 15-bromo-1-pentadecenyl;
2-iodovinyl, 2-iodo-1-methylvinyl, 3
-Iodo-1-propenyl, 3-iodo-2-propenyl, 4-iodo-1-butenyl, 4-iodo-2-butenyl, 3-iodo-2-methyl-2-propenyl, 4-
Iodo-1,3-butadienyl, 5-iodo-1-pentenyl, 5-iodo-2-pentenyl, 4-iodo-1
-Methyl-1-butenyl, 6-iodo-1-hexenyl, 6-iodo-2-hexenyl, 5-iodo-1-methyl-1-pentenyl, 6-iodo-1,4-hexadienyl, 7-iodo-1 -Heptenyl, 7-iodo-
1,6-heptadienyl, 7-iodo-1,3,6-heptatrienyl, 8-iodo-1-octenyl, 4-iodo-1-butyl-2-butenyl, 5-iodo-4-propyl-2-pentenyl, 6-iodo-3,5-dimethyl-1-hexenyl, 9-iodo-1-nonenyl, 10
-Iodo-1-decenyl, 11-iodo-1-undecenyl, 12-iodo-1-dodecenyl, 11-iodo-
Substituted with iodo such as 1,7-dimethyl-1,5,7,9-undecatetraenyl, 13-iodo-1-tridecenyl, 14-iodo-1-tetradecenyl or 15-iodo-1-pentadecenyl. A linear or branched chain having chloro, bromo or iodo as a substituent, having 1 to 4 double bonds, and having 5 to 14 carbon atoms; And more preferably a linear or branched hydrocarbon group having chloro or bromo, having 1 or 2 double bonds, and having 5 to 7 carbon atoms. It is.

When the epoxyethane derivative having the above general formula (I) of the present invention has a basic group according to a conventional method, it can be converted into an acid addition salt. Such salts are, for example, salts of hydrohalic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid; inorganic acids such as nitrates, perchlorates, sulfates, phosphates Salts; salts of lower alkanesulfonic acids such as methanesulfonic acid, trifluoromethanesulfonic acid, ethanesulfonic acid; benzenesulfonic acid, p
Salts of arylsulfonic acids such as toluenesulfonic acid; salts of amino acids such as glutamic acid and aspartic acid; acetic acid, fumaric acid, tartaric acid, oxalic acid, maleic acid, malic acid, succinic acid, benzoic acid, mandelic acid, ascorbic acid And carboxylic acids such as lactic acid, gluconic acid and citric acid. Preferably, it is a salt of hydrohalic acid.

Further, when the epoxyethane derivative having the general formula (I) has an acidic group, it can be converted into a metal salt according to a conventional method. Examples of such salts include alkali metal salts such as lithium, sodium and potassium; alkaline earth metal salts such as calcium, barium and magnesium; aluminum salts; and the like. Preferably, it is an alkali metal salt.

The epoxyethane derivative having the general formula (I) or a salt thereof has various isomers, for example, cis-trans isomer. In the general formula (I), all of these isomers and a mixture of equal and unequal amounts of these isomers are represented by a single formula. Therefore, in the present invention, all of these isomers and a mixture of these isomers are also included.

Further, in the present invention, when the epoxyethane derivative having the general formula (I) or a salt thereof forms a solvate (for example, a hydrate), it includes all of them.

In the epoxyethane derivative having the general formula (I), preferably, (1) an epoxyethane derivative wherein R ¹ is a linear or branched alkyl group having 1 to 4 carbon atoms, or Its salt.

(2) An epoxyethane derivative or a salt thereof, wherein R ¹ is an alkyl group having 1 or 2 carbon atoms.

(3) An epoxyethane derivative or a salt thereof in which R ¹ is a methyl group.

(4) R ¹ is a straight-chain or branched alkoxy having 1 to 4 carbon atoms and an alkoxy consisting of a straight-chain or branched alkyl having 1 to 4 carbon atoms. An epoxyethane derivative or a salt thereof, which is an alkyl group.

(5) An epoxyethane derivative or a salt thereof, wherein R ¹ is an alkoxyalkyl group comprising an alkoxy having 1 or 2 carbons and an alkyl having 1 or 2 carbons.

(6) An epoxyethane derivative or a salt thereof, wherein R ¹ is a linear or branched hydroxyalkyl group having 1 to 4 carbon atoms.

(7) An epoxyethane derivative or a salt thereof, wherein R ¹ is a hydroxyalkyl group having 1 or 2 carbon atoms.

(8) An epoxyethane derivative or a salt thereof, wherein R ² is a hydrogen atom.

(9) An epoxyethane derivative or a salt thereof, wherein R ² is a protecting group for a hydroxyl group.

(10) R ³ is an unsubstituted C 5 -C 1
An epoxyethane derivative or a salt thereof, which is a linear or branched alkyl group having four.

(11) An epoxyethane derivative or a salt thereof, wherein R ³ is an unsubstituted linear or branched alkyl group having 10 to 14 carbon atoms.

(12) An epoxyethane derivative or a salt thereof, wherein R ³ is a straight-chain or branched-chain alkyl group having 5 to 14 carbon atoms and having hydroxy as a substituent.

(13) An epoxyethane derivative or a salt thereof, wherein R ³ is a linear or branched alkyl group having 5 to 7 carbon atoms and having hydroxy as a substituent. (14) R ³ has formyl as a substituent and has 4 carbon atoms
An epoxyethane derivative or a salt thereof, which is a linear or branched alkyl group having from 13 to 13. (15) R ³ has formyl as a substituent and has 4 carbon atoms
An epoxyethane derivative or a salt thereof, which is a linear or branched alkyl group having from 6 to 6;

(16) R ³ has a straight-chain or branched-chain alkoxycarbonyl having 2 to 5 carbon atoms as a substituent, and a straight-chain or branched-chain having 5 to 14 carbon atoms having an alkoxycarbonyl. An epoxyethane derivative or a salt thereof, which is an alkyl group.

(17) R ³ has a carbon number of 5 having an alkoxycarbonyl having 2 or 3 carbons as a substituent.
An epoxyethane derivative or a salt thereof, which is a linear or branched alkyl group having 7 to 7 carbon atoms.

(18) An epoxyethane derivative or a salt thereof, wherein R ³ is a linear or branched alkyl group having 5 to 14 carbon atoms and having chloro, bromo or iodo as a substituent.

(19) An epoxyethane derivative or a salt thereof, wherein R ³ is a linear or branched alkyl group having 5 to 7 carbon atoms having chloro or bromo as a substituent.

(20) An epoxyethane derivative wherein R ³ is a linear or branched hydrocarbon group having 1 to 4 unsubstituted double bonds and 5 to 14 carbon atoms, or an epoxyethane derivative thereof. salt.

(21) An epoxyethane derivative wherein R ³ is a linear or branched hydrocarbon group having 1 or 2 unsubstituted double bonds and 5 to 7 carbon atoms, or an epoxyethane derivative thereof. salt.

(22) R ³ has hydroxy as a substituent, has 1 to 4 double bonds, and has 5 to 1 carbon atoms.
An epoxyethane derivative which is a linear or branched hydrocarbon group having four or a salt thereof.

(23) R ³ has hydroxy as a substituent, has one or two double bonds, and has 5 to 7 carbon atoms.
An epoxyethane derivative or a salt thereof, which is a linear or branched hydrocarbon group having a single bond.

(24) R ³ has formyl as a substituent, has 1 to 4 double bonds, and has 4 to 13 carbon atoms.
An epoxyethane derivative or a salt thereof, which is a linear or branched hydrocarbon group having a single bond.

(25) R ³ is a straight-chain or branched hydrocarbon group having formyl as a substituent, one or two double bonds, and 4 to 6 carbon atoms. Epoxyethane derivatives or salts thereof.

(26) R ³ has a straight-chain or branched alkoxycarbonyl having 2 to 5 carbon atoms as a substituent, has 1 to 4 double bonds, and has 5 to 5 carbon atoms. An epoxyethane derivative or a salt thereof, which is a linear or branched hydrocarbon group having 14 groups.

(27) R ³ has a substituted or unsubstituted alkoxycarbonyl having 2 or 3 carbon atoms, has 3 or 4 double bonds, and has a straight or branched chain having 12 to 14 carbon atoms. An epoxyethane derivative or a salt thereof, which is a branched hydrocarbon group.

(28) R ³ has chloro, bromo or iodo as a substituent, has 1 to 4 double bonds,
An epoxyethane derivative or a salt thereof, which is a linear or branched hydrocarbon group having 5 to 14 carbon atoms.

(29) R ³ has chloro or bromo as a substituent, has one or two double bonds, and has 5 carbon atoms.
An epoxyethane derivative or a salt thereof, which is a straight-chain or branched-chain hydrocarbon group having 7 to 7 carbon atoms.

(30) An epoxyethane derivative or a salt thereof, wherein R ³ is a linear or branched alkoxy group having 1 to 4 carbon atoms.

(31) An epoxyethane derivative or a salt thereof, wherein R ³ is a linear or branched alkoxy group having 3 or 4 carbon atoms.

(32) An epoxyethane derivative or a salt thereof, wherein R ³ is a hydroxy group.

(33) R ³ is a group having the formula —N (R ^5a ) (R ^6a ) (provided that R ^5a is a linear or branched alkyl group having 1 to 4 carbon atoms or a carbon atom R ^6a represents a linear or branched alkyl group having 1 to 4 carbon atoms, and R ^6a represents a linear or branched alkyl group having 1 to 4 carbon atoms. An ethane derivative or a salt thereof.

(34) R ³ is a group having the formula —N (R ^5b ) (R ^6b ) (provided that R ^5b is an alkyl group having 1 or 2 carbon atoms or an alkoxy group having 1 or 2 carbon atoms) R ^6b represents an alkyl group having 1 or 2 carbon atoms.) Or a salt thereof.

(35) An epoxyethane derivative or a salt thereof, wherein R ⁴ is a linear or branched alkoxy group having 1 to 4 carbon atoms.

(36) An epoxyethane derivative or a salt thereof, wherein R ⁴ is a linear or branched alkoxy group having 3 or 4 carbon atoms.

(37) R ⁴ is a group having the formula —NH (R ^7a ) (provided that R ^7a is a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms). )
Or a salt thereof.

(38) An epoxyethane derivative or a salt thereof in which R ⁴ is a group having the formula —NH (R ^7b ) (where R ^7b represents a hydrogen atom or an alkyl group having 1 or 2 carbon atoms). .

(39) An epoxyethane derivative or a salt thereof, wherein R ⁴ is a group having the formula —NH (R ^7c ) (where R ^7c represents a hydrogen atom).

(40) An epoxyethane derivative or a salt thereof in which R ² and R ⁴ are bonded together to show a single bond.

(41) An epoxyethane derivative or a salt thereof in which the substituted α is hydroxy, formyl, or a linear or branched alkoxycarbonyl having 2 to 7 carbon atoms.

(42) An epoxyethane derivative or a salt thereof in which the substituted α is hydroxy, formyl, or a linear or branched alkoxycarbonyl having 2 to 5 carbon atoms.

(43) An epoxyethane derivative or a salt thereof, wherein the substituted α is hydroxy, formyl or alkoxycarbonyl having 2 or 3 carbon atoms.

[0077] In addition, (1) to select R ¹ from (7), (8) or (9) to select the R ² from, select R ³ from to (10) to (34), (35) Or (3
Select R ⁴ to 9), (40) to select the R ² and R ⁴ from, select the substituent α from (41) to (43),
Compounds in any combination are also suitable.

For example, in the epoxyethane derivative having the general formula (I), (44) R ¹ is a linear or branched alkyl group having 1 to 4 carbon atoms, 1 to 4 carbon atoms. An alkoxyalkyl group consisting of a linear or branched alkoxy having 1 to 4 carbon atoms and a linear or branched alkyl having 1 to 4 carbon atoms, or a linear or branched alkyl having 1 to 4 carbon atoms R ² is a hydrogen atom or a protecting group for a hydroxyl group; R ³ is an unsubstituted linear or branched alkyl group having 5 to 14 carbon atoms; A straight-chain or branched alkyl group having 5 to 14 carbon atoms having hydroxy as a substituent, a straight-chain or branched alkyl group having 4 to 13 carbon atoms having formyl as a substituent. A branched-chain alkyl group, a straight-chain or branched-chain alkyl having 5 to 14 carbon atoms having a straight-chain or branched-chain alkoxycarbonyl having 2 to 5 carbon atoms as a substituent. A straight-chain or branched alkyl group having 5 to 14 carbon atoms having chloro, bromo or iodo as a group or substituent, having 1 to 4 unsubstituted double bonds, and having 5 to 5 carbon atoms. A straight-chain or branched hydrocarbon group having 14 carbon atoms, a straight-chain or branched chain having hydroxy as a substituent, having 1 to 4 double bonds, and having 5 to 14 carbon atoms A linear hydrocarbon group having 1 to 4 double bonds and having 4 to 13 carbon atoms, a linear or branched hydrocarbon group having formyl as a substituent, Having 2 to 5 carbon atoms It has a linear or branched alkoxycarbonyl having four to 1 double bonds, carbon atoms 5
A straight-chain or branched hydrocarbon group having 1 to 14 carbon atoms, having chloro, bromo or iodo as a substituent, having 1 to 4 double bonds, and having 5 to 14 carbon atoms.
Or a straight-chain or branched-chain hydrocarbon group having 1 to 4 carbon atoms, a straight-chain or branched-chain alkoxy group having 1 to 4 carbon atoms, a hydroxy group, or a compound of the formula -N ( ^R5a ) (R
^6a ) (wherein R ^5a is a linear or branched alkyl group having 1 to 4 carbon atoms or a linear or branched alkoxy group having 1 to 4 carbon atoms) R ^6a represents a linear or branched alkyl group having 1 to 4 carbon atoms);
⁴ is a linear or branched alkoxy group having 1 to 4 carbon atoms or a group having the formula —NH (R ^7a ), provided that R ^7a is a hydrogen atom or a straight chain having 1 to 4 carbon atoms. R ² and R ⁴ are bonded together to form a single bond; an epoxyethane derivative or a salt thereof.

(45) R ¹ is a linear or branched alkyl group having 1 to 4 carbon atoms or a carbon number of 1
R ² is a hydrogen atom or a protecting group for a hydroxyl group; R ³ is an unsubstituted linear group having 5 to 14 carbon atoms. Or a branched-chain alkyl group, a straight-chain or branched-chain hydrocarbon group having hydroxy as a substituent, having 1 to 4 double bonds, and having 5 to 14 carbon atoms. A straight-chain or branched-chain hydrocarbon group having 1 to 4 double bonds and 4 to 13 carbon atoms, having 2 to 5 carbon atoms as a substituent, Having a linear or branched alkoxycarbonyl, having 1 to 4 double bonds,
A linear or branched hydrocarbon group having 5 to 14 carbon atoms, a linear or branched alkoxy group having 1 to 4 carbon atoms, a hydroxy group, or
A group having the formula —N (R ^5a ) (R ^6a ), wherein R ^5a is a linear or branched alkyl group having 1 to 4 carbon atoms or a linear group having 1 to 4 carbon atoms. R ^6a represents a linear or branched alkyl group having 1 to 4 carbon atoms, and R ⁴ represents a linear or branched alkyl group having 1 to 4 carbon atoms. A linear or branched alkoxy group having the formula
(R ^7a) groups having a (wherein, R ^7a is from 1 number hydrogen atom or a C a linear or branched alkyl radical having 4 carbon atoms.) In there; or, R ² and R ⁴ Linked together to form a single bond; an epoxyethane derivative or a salt thereof.

(46) R ¹ is an alkyl group having 1 or 2 carbon atoms, an alkoxyalkyl group consisting of an alkoxy having 1 or 2 carbon atoms and an alkyl having 1 or 2 carbon atoms, or an alkyl group having 1 or 2 carbon atoms. R ² is a hydrogen atom or a protecting group for a hydroxyl group; R ³ is an unsubstituted hydroxyalkyl group having 2 carbon atoms;
A straight or branched alkyl group having from 14 to 14 carbon atoms, a straight or branched alkyl group having 5 to 7 carbon atoms having hydroxy as a substituent, and a carbon atom having formyl as a substituent. A straight-chain or branched-chain alkyl group having 4 to 6 carbon atoms, a straight-chain or branched-chain alkyl group having 5 to 7 carbon atoms having an alkoxycarbonyl having 2 or 3 carbon atoms as a substituent. A linear or branched alkyl group having 5 to 7 carbon atoms having chloro or bromo as a substituent, having 1 or 2 unsubstituted double bonds, and having 5 to 7 carbon atoms. A straight-chain or branched hydrocarbon group having 7 carbon atoms, having a hydroxy as a substituent, having 1 or 2 double bonds, and having 5 to 7 carbon atoms; A branched or branched hydrocarbon group, having formyl as a substituent, having one or two double bonds, and having 4 to 6 carbon atoms, a linear or branched hydrocarbon group; Having an alkoxycarbonyl having 2 or 3 carbon atoms, and having a double bond of 3 or 4
A straight or branched hydrocarbon group having 12 to 14 carbon atoms, having chloro or bromo as a substituent, having one or two double bonds, and having 5 or more carbon atoms. A linear or branched hydrocarbon group having 7 carbon atoms, a linear or branched alkoxy group having 3 or 4 carbon atoms, a hydroxy group, or a compound of the formula -N
A group having (R ^5b ) (R ^6b ) (provided that R ^5b represents an alkyl group having 1 or 2 carbon atoms or an alkoxy group having 1 or 2 carbon atoms. R ^6b represents 1 or 2 carbon atoms) Wherein R ⁴ is a linear or branched alkoxy group having 3 or 4 carbon atoms or a group having the formula —NH (R ^7b ), provided that R ^7b is A hydrogen atom or an alkyl group having 1 or 2 carbon atoms); or R ² and R ⁴
Are bonded together to form a single bond; an epoxyethane derivative or a salt thereof.

(47) R ¹ is an alkyl group having 1 or 2 carbon atoms; R ² is a hydrogen atom or a protecting group for a hydroxyl group; R ³ is an unsubstituted straight-chain having 10 to 14 carbon atoms. Chain or branched alkyl group, straight or branched chain hydrocarbon group having hydroxy as a substituent, having one or two double bonds, and having 5 to 7 carbon atoms A straight-chain or branched hydrocarbon group having formyl as a substituent, having one or two double bonds and having 4 to 6 carbon atoms, and having 2 or 3 carbon atoms as a substituent A linear or branched hydrocarbon group having 3 or 4 double bonds, and having 12 to 14 carbon atoms,
A linear or branched alkoxy group having 3 or 4 carbon atoms, a hydroxy group, or a compound of the formula -N ( ^R5b )
A group having (R ^6b ) (provided that R ^5b has 1 or 2 carbon atoms)
An alkyl group having 1 or 2 or an alkoxy group having 1 or 2 carbon atoms. R ^6b represents an alkyl group having 1 or 2 carbon atoms. And R ⁴ has 3 carbon atoms.
Or a linear or branched alkoxy group having four or a group having the formula —NH (R ^7b ) (provided that R ^7b
Represents a hydrogen atom. Or R ² and R ⁴ are bonded together to form a single bond; an epoxyethane derivative or a salt thereof.

Specific examples of the epoxyethane derivative having the general formula (I) of the present invention include the following compounds.

In Tables 1 and 2, abbreviations indicate the following groups.

Bu: butyl, sBu: s-butyl, tB
u: t-butyl, Et: ethyl, Hex: hexyl,
Me: methyl, Pen: pentyl, Pr: propyl,
iPr: isopropyl, TBS: t-butyldimethylsilyl, TES: triethylsilyl, TMS: trimethylsilyl.

[0085]

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[0086]

[Table 1] Examples R ¹ R ² R ³ R ⁴ compounds No.──────────────────────────────────── 1-1 Me H OMe OMe 1-2 Me H OEt OEt 1-3 Me H OPr OPr 1-4 Me H OiPr OiPr 1-5 Me H OBu OBu 1-6 Me H OtBu OtBu 1-7 Me H OPen OPen 1-8 Me H OHex OHex 1-9 Me TMS OMe OMe 1-10 Me TES OMe OMe 1-11 Me TBS OMe OMe 1-12 Me TBS OEt OEt 1-13 Me TBS OPr OPr 1-14 Me TBS OiPr OiPr 1-15 Me TBS OBu OBu 1-16 Me TBS OtBu OtBu 1 -17 Me TBS OPen OPen 1-18 Me TBS OHex OHex 1-19 Et H OMe OMe 1-20 Et H OEt OEt 1-21 Et H OtBu OtBu 1-22 iPr H OMe OMe 1-23 iPr H OEt OEt 1- 24 iPr H OPr OPr 1-25 iPr H OiPr OiPr 1-26 iPr H OBu OBu 1-27 iPr H OtBu OtBu 1-28 iPr H OPen OPen 1-29 iPr H OHex OHex 1-30 (CH ₂ ) ₂ OH H OMe OMe 1-31 (CH ₂ ) ₂ OH H OEt OEt 1-32 (CH ₂ ) ₂ OH H OPr OPr 1-33 (CH ₂ ) ₂ OH H OiPr OiPr 1-34 (CH ₂ ) ₂ OH H OBu OBu 1-35 (CH ₂ ) ₂ OH H OtBu OtBu 1-36 (CH ₂ ) ₂ OH H OPen OPen 1-37 (CH ₂ ) ₂ OH H OHex OHex 1-38 Pr H OtBu OtBu 1-39 Bu H OtBu OtBu 1-40 tBu H OtBu OtBu 1-41 Pen H OtBu OtBu 1-42 Hex H OtBu OtBu 1-43 Pr TMS OtBu OtBu 1-44 Bu TMS OtBu OtBu 1-45 tBu TMS OtBu OtBu 1-46 Pen TMS OtBu OtBu 1-47 Hex TMS OtBu OtBu 1 -48 Pr TES OtBu OtBu 1-49 Bu TES OtBu OtBu 1-50 tBu TES OtBu OtBu 1-51 Pen TES OtBu OtBu 1-52 Hex TES OtBu OtBu 1-53 Me HN (OMe) Me OMe 1-54 Me HN ( OMe) Me OEt 1-55 Me HN (OMe) Me OtBu 1-56 Me TBS N (OMe) Me OMe 1-57 Me TBS N (OMe) Me OEt 1-58 Me TBS N (OMe) Me OtBu 1-59 iPr HN (OMe) Me OtBu 1-60 Me HN (OMe) Me NH ₂ 1-61 Me HN (OMe) Me NHMe 1-62 Me HN (OMe) Me NHEt 1-63 Me HN (OMe) Me NHPr 1- 64 Me HN (OMe) Me NHBu 1-65 iPr HN (OMe) Me NHMe 1-66 iPr HN (OMe) Me NHEt 1-67 iPr HN (OMe) Me NHPr 1-68 iPr HN (OMe) Me NHBu 1- 69 (CH ₂ ) ₂ OH HN (OMe) Me NHMe 1-70 (CH ₂ ) ₂ OH HN (OMe) Me NHEt 1-71 (CH ₂ ) ₂ OH HN (OMe) Me NHPr 1-72 (CH ₂ ) _{2 OH HN (OMe) Me NHBu} 1-73 Me TMS N (OMe) Me NH 2 1-74 Me TES N (OMe) Me NH 2 1-75 Me TBS N (OMe) Me NH 2 1-76 E t TBS N (OMe) Me NH 2 1-77 Pr TBS N (OMe) Me NH 2 1-78 iPr TBS N (OMe) Me NH 2 1-79 Bu TBS N (OMe) Me NH 2 1-80 (CH ₂ ) ₂ OH TBS N (OMe) Me NH ₂ 1-81 Me TBS N (OMe) Me NHMe 1-82 Me TBS N (OMe) Me NHEt 1-83 Me TBS N (OMe) Me NHPr 1-84 Me TBS N (OMe) Me NHBu 1-85 iPr TBS N (OMe) Me NHMe 1-86 iPr TBS N (OMe) Me NHEt 1-87 iPr TBS N (OMe) Me NHPr 1-88 iPr TBS N (OMe) Me NHBu 1-89 (CH ₂ ) ₂ OH TBS N (OMe) Me NHMe 1-90 (CH ₂ ) ₂ OH TBS N (OMe) Me NHEt 1-91 (CH ₂ ) ₂ OH TBS N (OMe) Me NHPr 1- _{92 (CH 2) 2 OH TBS} N (OMe) Me NHBu 1-93 Me TBS Et NH 2 1-94 Me TBS CH = CH 2 NH 2 1-95 Me TBS CMe = CH 2 NH 2 1-96 Me TBS iPr NH ₂ 1-97 Me TBS Bu NH ₂ 1-98 Me TBS tBu NH ₂ 1-99 Me TBS (CH ₂ ) ₄ CH ₃ NH ₂ 1-100 Me TBS (CH ₂ ) ₅ CH ₃ NH ₂ 1-101 Me TBS (CH ₂ ) ₆ CH ₃ NH ₂ 1-102 Me TBS (CH ₂ ) ₇ CH ₃ NH ₂ 1-103 Me TBS (CH ₂ ) ₈ CH ₃ NH ₂ 1-104 Me TBS (CH ₂ ) ₉ CH ₃ NH ₂ 1-105 Me TBS (CH ₂ ) ₁₀ CH ₃ NH ₂ 1-106 Me TBS (CH ₂ ) ₁₁ CH ₃ NH ₂ 1-107 Me TBS CMe = CH (CH ₂ ) ₃ OH NH ₂ 1-108 Me TMS CMe = CH (CH ₂ ) ₃ OH NH ₂ 1-109 Me TES CMe = CH (CH ₂ ) ₃ OH NH ₂ 1-110 Me TBS CMe = CH (CH ₂ ) ₂ CHO NH ₂ 1-111 Me TMS CMe = CH (CH ₂ ) ₂ CHO NH ₂ 1-112 Me TES CMe = CH (CH ₂ ) ₂ CHO NH ₂ 1-113 Me TBS CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NH ₂ 1-114 Me TMS CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NH ₂ 1-115 Me TES CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NH ₂ 1-116 iPr TBS CMe = CH (CH ₂ ) ₃ OH NH ₂ 1-117 iPr TBS CMe = CH (CH ₂ ) ₂ CHO NH ₂ 1-118 iPr TBS CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NH ₂ 1-119 (CH ₂ ) ₂ OH TBS CMe = CH (CH ₂ ) ₃ OH NH ₂ 1-120 (CH ₂ ) ₂ OH TBS CMe = CH (CH ₂ ) ₂ CHO NH ₂ 1-121 (CH ₂ ) ₂ OH TBS CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC ( COOMe) = CHMe NH ₂ 1-122 Me TBS Et NHMe 1-123 Me TBS CH = CH ₂ NHMe 1-124 Me TBS CMe = CH ₂ NHMe 1-125 Me TBS iPr NHMe 1-126 Me TBS Bu NHMe 1-127 Me TBS (CH ₂ ) ₈ CH ₃ NHMe 1-128 Me TBS (CH ₂ ) ₉ CH ₃ NHMe 1-129 Me TBS (CH ₂ ) ₁₀ CH ₃ NHMe 1-130 Me TBS (CH ₂ ) ₁₁ CH ₃ NHMe 1 -131 Me TBS CMe = CH (CH ₂ ) ₃ OH NHMe 1-132 Me TBS CMe = CH (CH ₂ ) ₂ CHO NHMe 1-133 Me TBS CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NHMe 1-134 Me TBS Et NHEt 1-135 Me TBS CH = CH ₂ NHEt 1-136 Me TBS CMe = CH ₂ NHEt 1-137 Me TBS iPr NHEt 1-138 Me TBS Bu NHEt 1-139 Me TBS (CH ₂ ) ₈ CH ₃ NHEt 1-140 Me TBS (CH ₂ ) ₉ CH ₃ NHEt 1-141 Me TBS (CH ₂ ) ₁₀ CH ₃ NHEt 1-142 Me TBS (CH ₂ ) ₁₁ CH ₃ NHEt 1-143 Me TBS CMe = CH (CH ₂ ) ₃ OH NHEt 1-144 Me TBS CMe = CH (CH ₂ ) ₂ CHO NHEt 1-145 Me TBS CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NHEt 1 -146 Me TBS CMe = CH (CH ₂ ) ₃ OH NHPr 1-147 Me TBS CMe = CH (CH ₂ ) ₂ CHO NHPr 1-148 Me TBS CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NHPr 1-149 Me TBS CMe = CH (CH ₂ ) ₃ OH NHiPr 1-150 Me TBS CMe = CH (CH ₂ ) ₂ CHO NHiPr 1-151 Me TBS CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NHiPr 1-152 Me TBS Et NHBu 1-153 Me TBS CH = CH ₂ NHBu 1-154 Me TBS CMe = CH ₂ NHBu 1-155 Me TBS iPr NHBu 1-156 Me TBS Bu NHBu 1- 157 Me TBS (CH ₂ ) ₈ CH ₃ NHBu 1-158 Me TBS (CH ₂ ) ₉ CH ₃ NHBu 1-159 Me TBS (CH ₂ ) ₁₀ CH ₃ NHBu 1-160 Me TBS (CH ₂ ) ₁₁ CH ₃ NHBu 1-161 Me TBS CMe = CH (CH ₂ ) ₃ OH NHBu 1-162 Me TBS CMe = CH (CH ₂ ) ₂ CH O NHBu 1-163 Me TBS CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NHPen 1-164 Me TBS CMe = CH (CH ₂ ) ₃ OH NHtBu 1-165 Me TBS CMe = CH ( CH ₂ ) ₂ CHO NHtBu 1-166 Me TBS CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NHtBu 1-167 Me TBS CMe = CH (CH ₂ ) ₃ OH NHPen 1-168 Me TBS CMe = CH (CH ₂ ) ₂ CHO NHPen 1-169 Me TBS CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NHPen 1-170 Me TBS CMe = CH (CH ₂ ) ₃ OH NHHex 1 -171 Me TBS CMe = CH (CH ₂ ) ₂ CHO NHHex 1-172 Me TBS CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NHHex 1-173 Me TBS CMe = CH (CH ₂ ) ₃ OH NHPr 1-174 Me TBS CMe = CH (CH ₂ ) ₂ CHO NHPr 1-175 Me TBS CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NHPr 1-176 Me H Et NH ₂ 1-177 Me H CH = CH ₂ NH ₂ 1-178 Me H CMe = CH ₂ NH ₂ 1-179 Me H CMe = CHCH ₃ NH ₂ 1-180 Me H CMe = CH (CH ₂ ) ₃ CH ₃ NH ₂ 1-181 Me H iPr NH ₂ 1-182 Me H Bu NH ₂ 1-183 Me H sBu NH ₂ 1-184 Me H iBu NH ₂ 1-185 Me H tBu NH ₂ 1-186 Me H (CH ₂ ) ₄ CH ₃ NH ₂ 1-187 Me H (CH ₂ ) ₅ CH ₃ NH ₂ 1-188 Me H (CH ₂ ) ₆ CH ₃ NH ₂ 1-189 Me H (CH ₂ ) ₇ CH ₃ NH ₂ 1-190 Me H (CH ₂ ) ₈ CH ₃ NH ₂ 1-191 Me H (CH ₂ ) ₉ CH ₃ NH ₂ 1-192 Me H (CH ₂ ) ₁₀ CH ₃ NH ₂ 1-193 Me H (CH ₂ ) ₁₁ CH ₃ NH ₂ 1- 194 Me H CMe = CH (CH ₂ ) ₃ OH NH ₂ 1-195 Me H CMe = CH (CH ₂ ) ₂ CHO NH ₂ 1-196 Me H CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe ) = CHMe NH ₂ 1-197 Me H Et NHMe 1-198 Me H CH = CH ₂ NHMe 1-199 Me H CMe = CH ₂ NHMe 1-200 Me H iPr NHMe 1-201 Me H Bu NHMe 1-202 Me H (CH ₂ ) ₈ CH ₃ NHMe 1-203 Me H (CH ₂ ) ₉ CH ₃ NHMe 1-204 Me H (CH ₂ ) ₁₀ CH ₃ NHMe 1-205 Me H (CH ₂ ) ₁₁ CH ₃ NHMe 1- 206 Me H CMe = CH (CH ₂ ) ₃ OH NHMe 1-207 Me H CMe = CH (CH ₂ ) ₂ CHO NHMe 1-208 Me H CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NHMe 1-209 Me H Et NHEt 1-210 Me H CH = CH ₂ NHEt 1-211 Me H CMe = CH ₂ NHEt 1-212 Me H iPr NHEt 1-213 Me H Bu NHEt 1-214 Me H (CH ₂ ) ₈ CH ₃ NHEt 1-215 Me H (CH ₂ ) ₉ CH ₃ NHEt 1-216 Me H (CH ₂ ) ₁₀ CH ₃ NHEt 1-217 Me H (CH ₂ ) ₁₁ CH ₃ NHEt 1-218 Me H CMe = CH (CH ₂ ) ₃ OH NHEt 1-219 Me H CMe = CH (CH ₂ ) ₂ CHO NHEt 1-220 Me H CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NHEt 1 -221 Me H CMe = CH (CH ₂ ) ₃ OH NHPr 1-222 Me H CMe = CH (CH ₂ ) ₂ CHO NHPr 1-223 Me H CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NHPr 1-224 Me H CMe = CH ( CH ₂ ) ₃ OH NHiPr 1-225 Me H CMe = CH (CH ₂ ) ₂ CHO NHiPr 1-226 Me H CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NHiPr 1-227 Me H Et NHBu 1-228 Me H CH = CH ₂ NHBu 1-229 Me H CMe = CH ₂ NHBu 1-230 Me H iPr NHBu 1-231 Me H Bu NHBu 1-232 Me H (CH ₂ ) ₈ CH ₃ NHBu 1 -233 Me H (CH ₂ ) ₉ CH ₃ NHBu 1-234 Me H (CH ₂ ) ₁₀ CH ₃ NHBu 1-235 Me H (CH ₂ ) ₁₁ CH ₃ NHBu 1-236 Me H CMe = CH (CH ₂ ) ₃ OH NHBu 1-237 Me H CMe = CH (CH ₂ ) ₂ CHO NHBu 1-238 Me H CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NHBu 1-239 Me H CMe = CH (CH ₂ ) ₃ OH NHPen 1-240 Me H CMe = CH (CH ₂ ) ₂ CHO NHPen 1-241 Me H CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NHPen 1-242 Me H CMe = CH (CH ₂ ) ₃ OH NHHex 1-243 Me H CMe = CH (CH ₂ ) ₂ CHO NHHex 1-244 Me H CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NHHex 1-245 Et H CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NH ₂ 1-246 Pr H CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NH ₂ 1-247 Bu HC Me = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NH ₂ 1-248 Pen H CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NH ₂ 1-249 Hex H CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NH ₂ 1-259 iPr H CMe = CH (CH ₂ ) ₃ OH NH ₂ 1-251 iPr H CMe = CH (CH ₂ ) ₂ CHO NH ₂ 1-252 iPr H CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NH ₂ 1-253 (CH ₂ ) ₂ OH H CMe = CH (CH ₂ ) ₃ OH NH ₂ 1- 254 (CH ₂ ) ₂ OH H CMe = CH (CH ₂ ) ₂ CHO NH ₂ 1-255 (CH ₂ ) ₂ OH H CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NH ₂ 1 -256 (CH ₂ ) ₃ OH H CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NH ₂ 1-257 (CH ₂ ) ₄ OH H CMe = CH (CH ₂ ) ₂ CH = CHCMe = CHC (COOMe) = CHMe NH ₂に お い て In the above exemplified compound 1) Suitable compounds include 1-1, 1-6, 1-16, 1-27,
1-35, 1-60, 1-65, 1-73, 1-75, 1-78, 1-80, 1-93, 1-
95, 1-104, 1-105, 1-106, 1-107, 1-110, 1-113
, 1-116, 1-117, 1-118, 1-119, 1-120, 1-121
, 1-176, 1-178, 1-180, 1-191, 1-192, 1-193
, 1-196, 1-206, 1-207, 1-208, 1-218, 1-219
, 1-220, 1-245, 1-246, 1-250, 1-251, 1-252
, 1-253, 1-254, and 1-255.

2) More preferred compounds include 1-6 and 1-
60, 1-75, 1-78, 1-80, 1-93, 1-107, 1-110, 1-113
, 1-118, 1-121, 1-176, 1-196, 1-252, and 1-255.

3) Examples of the most preferable compound include the following: Exemplified Compound No. 1-6) 3- (1-hydroxyethyl) oxirane-2,2-dicarboxylic acid di (t-butyl) ester 1-60) 3- (1) -Hydroxyethyl) oxirane-2,2-dicarboxylic acid amide methoxy-methylamide 1-75) 3- (1- (t-butyldimethylsilyloxy) ethyl) oxirane-2,2-dicarboxylic acid amide methoxy-methylamide 1- 93) 3- (1- (t-butyldimethylsilyloxy) ethyl) -2-propionyloxirane-2-carboxylic acid amide 1-107) 3- (1- (t-butyldimethylsilyloxy) ethyl) -2- (6-Hydroxy-2-methyl-2-hexenoyl) oxirane-2-carboxylic acid amide 1-110) 3- (1 (T-butyldimethylsilyloxy) ethyl) -2- (2-methyl-6-oxo-2-hexenoyl) oxiran-2-carboxylic acid amide 1-113) 11- (3- (1- (t-butyldimethyl) Silyloxy) ethyl) -2-carbamoyloxiranyl) -2-ethylidene-4,10-dimethyl-11-oxo-3,5,9-undecatrienoic acid methyl ester 1-176) 3- (1- (Hydroxyethyl) -2-propionyloxirane-2-carboxylic acid amide 1-196) 11- (2-carbamoyl-3- (1-hydroxyethyl) oxolanyl) -2-ethylidene-4,10-dimethyl-11-oxo Mso-3,5,9-undecatrienoic acid methyl ester.

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[0090]

[Table 2] {Example compound R ¹ R ³ number} ───────────────────────────────── 2-1 Me OH 2-2 Et OH 2-3 Pr OH 2- 4 iPr OH 2-5 (CH ₂ ) ₂ OH OH 2-6 Me OMe 2-7 Me OEt 2-8 Me OPr 2-9 Me OiPr 2-10 Me OBu 2-11 Me OtBu 2-12 Me OPen 2- 13 Me OHex 2-14 Me N (OMe) Me 2-15 Et N (OMe) Me 2-16 iPr N (OMe) Me 2-17 (CH ₂ ) ₂ OH N (OMe) Me ──────に お い て In the above exemplified compounds, 1) Suitable compounds are 2-1 and 2- 4, 2-5, 2-6,
2-14, 2-16, 2-17.

2) More preferred compounds include 2-1 and 2-
4, 2-14 and 2-16.

3) The most preferred compound is exemplified compound number 2-1) 4-methyl-2-oxo-3,6-dioxabicyclo [3.1.0] hexane-1-carboxylic acid 2-14 ) 4-Methyl-2-oxo-3,6-dioxabicyclo [3.1.0] hexane-1-carboxylic acid methoxy-methylamide.

[0093]

BEST MODE FOR CARRYING OUT THE INVENTION The epoxyethane derivative having the general formula (I) or a salt thereof according to the present invention can be easily produced according to the following method.

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[0095]

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In the above formula, R ¹ , R ⁵ , R ⁶ and R ⁷ are as defined above.

R ^3a and R ^4a are the same or different and have the same meaning as the above-mentioned alkoxy groups in the case where R ³ and R ⁴ represent a linear or branched alkoxy group having 1 to 6 carbon atoms. Show. R ^4b is the same or different and has the same meaning as the above-mentioned alkoxy group when R ³ and R ⁴ represent a linear or branched alkoxy group having 1 to 6 carbon atoms. R ⁹ represents a hydrocarbon group such as methyl, butyl and phenyl. A ¹ may have a substituted α, and may further have a linear or branched hydrocarbon group having 1 to 14 carbon atoms which may have 1 to 5 double bonds. Show. R ⁸ and A
² formula -A ² -CH joined together with the base -CH = CH-
ＣＨCH—R ⁸ to form a group having 1 to 15 carbon atoms which may have 1 to 5 double bonds. Shows a chain or branched hydrocarbon group. In A ³ , R ³ is substituted α
A linear or branched hydrocarbon group having 1 to 15 carbon atoms which may further have 1 to 5 double bonds Is equivalent to W ¹ , W ² , W ³ , W ⁴ , W ⁵ , W ⁶ ,
W ⁷ , W ⁸ and W ⁹ are the same or different and have the same meaning as the hydroxyl-protecting group when R ² represents a hydroxyl-protecting group. X ¹ , X ² , X ³ and X ⁴ are the same or different and represent a halogen atom such as chlorine or bromine.

Step 1 Introduction reaction of a protecting group for a hydroxyl group This step is a step of producing a compound having the general formula (2), and is achieved by protecting the hydroxyl group of the compound having the general formula (1). Is done.

Examples of the compound used for protecting a hydroxyl group include carboxylic acids such as acetic acid, propionic acid, butyric acid, benzoic acid and naphthalene carboxylic acid; acetic acid chloride;
Acid halide compounds such as acetic acid bromide, benzoyl chloride, benzoyl bromide and naphthoyl chloride; reactive derivatives of carboxylic acids such as acid anhydrides such as acetic anhydride, propionic anhydride and benzoic anhydride; benzyl chloride, benzyl bromide, -Nitrobenzyl bromide,
Aralkyl halide compounds such as 4-methoxybenzyl bromide; trityl halides such as trityl chloride and trityl bromide; dihydropyran, dihydrothiopyran, dihydrothiophene, 4-methoxy-5,6-
5- or 6-membered heterocyclic compound such as dihydro- (2H) pyran; alkoxy, alkylthio or aralkyloxy-substituted alkyl halide compound such as methoxymethyl chloride, methylthiomethyl chloride, ethoxyethyl chloride, benzyloxymethyl chloride; methyl Unsaturated ethers such as vinyl ether and ethyl vinyl ether; silyl compounds such as hexamethyldisilazane, trimethylsilyl chloride, tri-n-propylsilyl chloride, t-butyldimethylsilyl chloride, diphenyl-t-butylsilyl chloride; Suitable compounds can be mentioned.

For the method of introducing a protecting group, see “Protecti
ve Group in Organic Synthesis, 2nd edition
”, T.W. Greene & P.G.M. Wut; John Wiley
and Sons, Inc. , New York (1991). When a carboxylic acid compound is used, it is suitably performed in the presence of a condensing agent such as dicyclohexylcarbodiimide. When a reactive derivative of a carboxylic acid is used, it is suitably performed in the presence of an organic base such as triethylamine, pyridine, 4-N, N-dimethylaminopyridine, quinoline, and N, N-dimethylaniline.

The reaction is usually performed in the presence of a solvent. The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, and is preferably a halogenated hydrocarbon such as methylene chloride, chloroform, dichloroethane, carbon tetrachloride, or chlorobenzene. Hydrocarbons such as benzene, toluene, xylene and hexane; diethyl ether, tetrahydrofuran,
Ethers such as dioxane and dimethoxyethane; ketones such as acetone and methyl ethyl ketone; amides such as formamide, dimethylformamide and dimethylacetamide; preferably ethers (particularly tetrahydrofuran), amides (Especially dimethylformamide) and halogenated hydrocarbons (especially methylene chloride).

The reaction temperature varies depending on the solvent, raw materials, reagents and the like, but is usually from -20 ° C to 100 ° C, preferably from 0 ° C to 50 ° C.

The reaction time varies depending on the solvent, starting materials, reagents, reaction temperature and the like, but is usually from 10 minutes to 48 hours, preferably from 30 minutes to 24 hours.

When an aralkyl halide compound, trityl halide, alkoxy, alkylthio or aralkyloxy-substituted alkyl halide compound or silyl compound is used, the compound having the above general formula (1) is treated with sodium hydride, hydrogen hydride in an inert solvent. This is achieved by reacting with an alkali metal hydride such as potassium halide to produce an alkali metal salt, followed by reaction with a corresponding halide compound or a silylating reagent such as disilazane.

The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Examples thereof include ethers such as ether, tetrahydrofuran and dioxane; dimethylformamide, dimethylacetamide, Examples thereof include amides such as methylphosphoryltriamide; nitriles such as acetonitrile and benzonitrile; and sulfoxides such as dimethylsulfoxide. Preferred are amides. The reaction temperature varies depending on the solvent, raw materials, reagents and the like, but is usually 0 ° C to 100 ° C.

The reaction time varies depending on the solvent, raw materials, reagents, reaction temperature and the like, but is usually from 10 minutes to 3 hours.

Also, triethylamine, pyridine, 4-
N, N-dimethylaminopyridine, imidazole, 1,
Organic bases or sodium hydroxide, such as 8-diazabicyclo [5.4.0] undec-7-ene (DBU),
In the presence of an inorganic base such as potassium hydroxide or potassium carbonate, the compound having the general formula (1) can be reacted with a corresponding halide compound. 5 or 6
When using membered heterocyclic compounds or unsaturated ethers, the reaction is carried out in the presence or absence of an inert solvent with a small amount of an acid, for example a mineral acid such as hydrochloric acid, hydrobromic acid or picric acid, Trifluoroacetic acid, benzenesulfonic acid,
It is carried out in the presence of an organic acid such as 4-toluenesulfonic acid, camphorsulfonic acid.

The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Examples thereof include ethers such as ether, tetrahydrofuran and dioxane; methylene chloride, chloroform and tetrachloride Halogenated hydrocarbons such as carbon; or aromatic hydrocarbons such as benzene, toluene and xylene can be mentioned, but halogenated hydrocarbons are preferred. The reaction is also carried out by using an excess of a heterocyclic compound or a vinyl ether compound also as a solvent in the absence of an inert solvent.

The reaction temperature varies depending on the solvent, raw materials, reagents and the like, but is usually from 0 ° C. to 50 ° C.

The reaction time varies depending on the solvent, raw materials, reagents, reaction temperature and the like, but is usually 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, the reaction mixture is appropriately neutralized, and if insolubles are present, they are removed by filtration, and then an immiscible organic solvent such as water and ethyl acetate is added. It is obtained by separating and drying over anhydrous magnesium sulfate or the like, and then distilling off the solvent. If necessary, the obtained target compound can be further purified by a conventional method, for example, recrystallization, reprecipitation or chromatography.

Second Step Ester Reduction Reaction This step is a step for producing a compound having the general formula (3), and is achieved by reducing a compound having the general formula (2).

The reducing agent used is preferably diisobutylaluminum hydride.

The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent. Halogenated hydrocarbons such as chloride, chloroform, dichloroethane; benzene, toluene,
Aromatic hydrocarbons such as xylene; aliphatic hydrocarbons such as pentane and hexane; more preferably, aliphatic hydrocarbons such as pentane and hexane. This step is preferably performed under a stream of an inert gas such as nitrogen, helium, or argon.

The reaction temperature varies depending on the solvent, raw materials, reagents and the like, but is usually from -100 ° C to 0 ° C, preferably from -100 ° C.
78 ° C to -50 ° C.

The reaction time varies depending on the solvent, the starting material, the reagent, the reaction temperature and the like, but is usually from 10 minutes to 24 hours, preferably from 1 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, the reaction mixture is appropriately neutralized, and if insolubles are present, they are removed by filtration, and then an immiscible organic solvent such as water and ethyl acetate is added. It is obtained by separating and drying over anhydrous magnesium sulfate or the like, and then distilling off the solvent. If necessary, the obtained target compound can be further purified by a conventional method, for example, recrystallization, reprecipitation or chromatography.

Third Step Ester Reduction Reaction This step is a step of producing a compound having the general formula (4), and is achieved by reducing a compound having the general formula (2).

The reduction reaction is suitably performed by using a reducing agent. The reducing agent used is preferably a hydride compound such as lithium aluminum hydride, sodium borohydride and diisobutylaluminum hydride.

The reaction is suitably performed in the presence of a solvent. The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. Preferably, diethyl ether, tetrahydrofuran, dioxane,
Ethers such as dimethoxyethane; alcohols such as methanol and ethanol; and ethers (particularly tetrahydrofuran) and alcohols (particularly methanol).

The reaction temperature varies depending on the solvent, raw materials, reagents and the like, but is usually from -78 ° C to 100 ° C, preferably from -78 ° C to room temperature.

The reaction time varies depending on the solvent, the starting material, the reagent, the reaction temperature and the like, but is usually from 10 minutes to 24 hours, preferably from 1 to 10 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 appropriately neutralized, and if insolubles are present, they are removed by filtration, and then an immiscible organic solvent such as water and ethyl acetate is added. It is obtained by separating and drying over anhydrous magnesium sulfate or the like, and then distilling off the solvent. If necessary, the obtained target compound can be further purified by a conventional method, for example, recrystallization, reprecipitation or chromatography.

Fourth Step Oxidation Reaction of Alcohol This step is a step for producing a compound having the general formula (3), and is achieved by oxidizing a compound having the general formula (4).

The oxidation reaction is suitably performed by using an oxidizing agent. The oxidizing agent to be used is not particularly limited as long as it is used in a usual oxidation reaction, and preferably, manganese oxides such as manganese dioxide; chromic acid compounds such as chromic anhydride-pyridine complex ; DMSO
Reagents used for oxidation (dimethylsulfoxide and dicyclohexylcarbodiimide, oxalyl chloride, complex with acetic anhydride or phosphorus pentoxide or complex of pyridine-sulfuric anhydride); transition metal oxidizing agent such as tetrapropylammonium perthenate; 1,1,1-triacetoxy-1,1-dihydro-1,2-benzidoxo-
A high-valent iodine oxidizing agent such as ru-3 (1H) -one is exemplified, and a high-valent iodine oxidizing agent is more preferable.

The reaction is suitably performed in the presence of a solvent. The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting material to some extent. Preferably, aromatic hydrocarbons such as benzene, toluene and xylene; methylene chloride, chloroform, Halogenated hydrocarbons such as dichloroethane; esters such as ethyl acetate; ethers such as tetrahydrofuran, dioxane and dimethoxyethane; ketones such as acetone and methyl ethyl ketone; nitriles such as acetonitrile and isobutyronitrile And are preferably halogenated hydrocarbons (particularly methylene chloride) or ethers (particularly tetrahydrofuran).

The reaction temperature varies depending on the solvent, raw materials, reagents and the like, but is usually from -60 ° C to 50 ° C.

The reaction time varies depending on the solvent, raw materials, reagents, reaction temperature and the like, but is usually 1 to 16 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 appropriately neutralized, and if insolubles are present, they are removed by filtration, and then an immiscible organic solvent such as water and ethyl acetate is added. It is obtained by separating and drying over anhydrous magnesium sulfate or the like, and then distilling off the solvent. If necessary, the obtained target compound can be further purified by a conventional method, for example, recrystallization, reprecipitation or chromatography.

[0130] Fifth Step aldol reaction This step is a step for preparing a compound having the general formula (6), the general formula (3) compound with a compound having the general formula (5) having a (CH ₂ (COR ^3a ) (CO
R ^4a )) in the presence of a base.

The base used in this step is not particularly limited as long as it is used in a usual aldol reaction. Examples thereof include alkyl lithium such as methyl lithium and butyl lithium; lithium hydride, sodium hydride, and the like.
Alkali metal hydrides such as potassium hydride; alkali metal amides such as lithium amide, sodium amide, potassium amide; sodium methoxide, sodium ethoxide, potassium propoxide, sodium butoxide, potassium-t-butoxide, sodium-t −
Alkali metal alkoxides such as pentoxide; alkali metal disilazides such as lithium hexamethyldisilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide; preferably alkali metal hydrides, alkali Metal alkoxides or alkali metal disilazides, more preferably sodium hydride, potassium hydride, potassium-t-butoxide, sodium-t-pentoxide, sodium hexamethyldisilazide, potassium hexamethyldisilazide or lithium Hexamethyldisilazide, particularly preferably potassium hydride, potassium-t-butoxide, potassium hexamethyldisilazide or lithium hexamethyldisilazide.

Further, in this reaction, a Lewis acid can be used. The Lewis acid used is, for example, magnesium chloride, magnesium bromide, zinc chloride, zinc bromide, zinc iodide, aluminum chloride, titanium tetrachloride, boron trifluoride ether complex; preferably zinc chloride, It is zinc bromide.

The reaction is suitably performed in the presence of a solvent. The inert solvent used is not particularly limited as long as it is used in a usual aldol reaction, and examples thereof include aliphatic or alicyclic hydrocarbons such as hexane and cyclohexane; and aromatics such as benzene, toluene and xylene. Aromatic hydrocarbons; ethers such as diethyl ether, tetrahydrofuran, and dioxane; amides such as dimethylformamide and dimethylacetamide; sulfoxides such as dimethylsulfoxide; preferably aromatic hydrocarbons and ethers Amides or sulfoxides, more preferably aromatic hydrocarbons or ethers, and particularly preferably ethers (particularly tetrahydrofuran). This step is preferably performed under a stream of an inert gas such as nitrogen, helium, or argon.

The reaction temperature varies depending on the type of the starting compound, base, inert solvent and the like, but it is usually from -100 ° C to 50 ° C.
° C, preferably -100 ° C to room temperature, more preferably -100 ° C to 10 ° C, particularly preferably -100 ° C to -20 ° C.

The reaction time varies depending on the solvent, raw materials, reagents, reaction temperature and the like, but is usually 5 minutes to 3 hours, preferably 10 minutes to 1 hour, particularly preferably
10 to 30 minutes.

After completion of the reaction, the target compound is collected from the reaction mixture according to a conventional method. For example, after the completion of the reaction, the reaction mixture is poured into a cooled aqueous solution of saturated ammonium chloride or the like, extracted with a water-immiscible organic solvent such as hexane, and the obtained extract is diluted with saturated aqueous sodium hydrogen carbonate, saturated saline, or the like. After washing and drying, it can be obtained by distilling off the solvent. The obtained target compound can be further purified by a conventional method, for example, chromatography if necessary.

Step 6 Deprotection reaction of hydroxyl-protecting group This step is a step of producing a compound having the general formula (7), and removing the hydroxyl-protecting group of the compound having the general formula (6). Is achieved by doing The removal of the protecting group depends on its type, but is generally carried out by a method well known in the art as follows.

When the hydroxyl-protecting group is a lower aliphatic or aromatic acyl group, the removal is carried out by a usual hydrolysis or solvolysis reaction. As the acid or base to be used, an acid or base used in a general hydrolysis reaction or solvolysis reaction is used without any particular limitation. Usually, for example, lithium hydroxide, sodium hydroxide, potassium hydroxide, water It is preferably carried out under basic conditions using an alkali metal and alkaline earth metal hydroxide such as calcium oxide and barium hydroxide or an alkali metal carbonate such as potassium carbonate.

The reaction is suitably performed in the presence of a solvent. The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. Examples thereof include alcohols such as methanol, ethanol, n-propanol and isopropyl alcohol; diethyl ether, tetrahydrofuran, Ethers such as dioxane and dimethoxyethane; dialkyl sulfoxides such as dimethyl sulfoxide; and mixed solvents of these organic solvents and water.

The reaction temperature varies depending on the type of the starting compound, the base, the inert solvent and the like, but is usually from about room temperature to the reflux temperature of the solvent.

The reaction time varies depending on the solvent, raw materials, reagents, reaction temperature and the like, but is usually 1 hour to 12 hours.

When the protecting group for the hydroxyl group is an aralkyl group, this can be achieved by contacting the corresponding compound with a reducing agent in an inert solvent. Examples of the reducing agent used include alkali metals such as lithium, sodium and potassium. The reaction is suitably carried out in liquid ammonia or a mixed solvent of liquid ammonia and ethers such as ether and tetrahydrofuran. The reaction temperature is
The temperature is usually -78 ° C to -20 ° C, although it varies depending on the type of the starting compound, base, inert solvent and the like.

The reaction time varies depending on the solvent, raw materials, reagents, reaction temperature and the like, but is usually 20 minutes to 6 hours.

Further, when the protecting group is 4-methoxybenzyl group, the protecting group is removed by treatment with cerium ammonium nitrate and aqueous acetone at about room temperature, or by using an oxidizing agent such as dichlorodicyanoquinone or sodium persulfate. Is also removed. When the protecting group for the hydroxyl group is a heterocyclic group, a methyl group, a 1-alkoxyethyl group or a trityl group having an alkoxy or an aralkyloxy as a substituent, it can be easily achieved by contacting with an acid. Examples of the acid used include organic acids such as formic acid, acetic acid, trifluoroacetic acid, propionic acid, butyric acid, oxalic acid, malonic acid, methanesulfonic acid, benzenesulfonic acid, 4-toluenesulfonic acid, and camphorsulfonic acid;
Mineral acids such as hydrochloric acid, hydrobromic acid and sulfuric acid are preferably used.

The reaction is carried out in the presence or absence of a solvent, but it is preferable to use a solvent in order to carry out the reaction smoothly. The solvent used does not inhibit the reaction,
There is no particular limitation as long as it can dissolve the starting material to some extent, and examples thereof include water; alcohols such as methanol and ethanol; ethers such as tetrahydrofuran and dioxane; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; Ketones such as methyl ethyl ketone; or a mixed solvent of these organic solvents and water is preferably used.

The reaction temperature varies depending on the type of the starting compound, the base, the inert solvent and the like, but is usually from room temperature to the reflux temperature of the solvent.

The reaction time varies depending on the solvent, raw materials, reagents, reaction temperature and the like, but is usually 30 minutes to 10 hours. Alternatively, the methylthiomethyl group is also removed by treatment with mercuric chloride in aqueous acetonitrile.

When the protecting group of the hydroxyl group is a tri-lower alkyl or diaryl lower alkylsilyl group, it can be easily attained by contacting with water or water containing an acid or a base. When water containing an acid or a base is used, examples of the acid or base contained therein include organic acids such as formic acid, acetic acid, propionic acid, butyric acid, oxalic acid, and malonic acid; hydrochloric acid, hydrobromic acid, and sulfuric acid. Acids such as mineral acids or hydroxides of alkali metals and alkaline earth metals such as potassium hydroxide and calcium hydroxide; bases such as carbonates of alkali metals and alkaline earth metals such as potassium carbonate and calcium carbonate It is used without particular limitation. In the reaction, if water is used as a solvent, other solvents are not particularly required. When another solvent is used, a mixed solvent of water and an organic solvent such as ethers such as tetrahydrofuran and dioxane; alcohols such as methanol and ethanol is used.

The reaction temperature varies depending on the type of the starting compound, the base, the inert solvent and the like, but is usually preferably carried out at room temperature.

The reaction time varies depending on the solvent, raw materials, reagents, reaction temperature and the like, but is usually 30 minutes to 5 hours.

When the protecting group is a trimethylsilyl group, t-
In the case of a butyldimethylsilyl group or a diphenyl-t-butylsilyl group, tetrabutylammonium fluoride, triethylamine-trihydrofluoride is used in the presence of ethers such as tetrahydrofuran and dioxane; amides such as dimethylformamide. It is also achieved by processing.

After the completion of the reaction, the target compound for the reaction for removing the protecting group for the hydroxyl group is collected from the reaction mixture according to a conventional method. For example, after the reaction is completed, the solvent is appropriately distilled off under reduced pressure,
The reaction mixture is poured into ice-water without neutralization, neutralized as necessary, and then an appropriate organic solvent is added for extraction.The extract is washed with water and dried, and the solvent is distilled off from the extract. can get. Seventh Step Introduction Reaction of Protecting Group for Hydroxy Group This step is a step of producing a compound having the general formula (8), and is achieved by protecting the hydroxyl group of the compound having the general formula (7).

The reaction for introducing a protecting group for a hydroxyl group can be carried out according to the first step.

Eighth Step Halogenation Reaction This step is a step for producing a compound having the general formula (9), and is accomplished by substituting an active methylene hydrogen of the compound having the general formula (8) with halogen. Is done.

The reaction is carried out by reacting the compound having the general formula (8) with a halogenating agent in the presence of a base.

As the halogenating agent used in the reaction,
For example, haloimides such as N-chlorosuccinimide, N-bromosuccinimide, N-iodosuccinimide; halogens such as chlorine, bromine and iodine; preferably iodine, N-bromosuccinimide, -Iodosuccinimide.

The base used in the reaction is not particularly limited as long as it does not affect the reaction. Examples thereof include alkyllithium such as methyllithium and butyllithium; and alkali metal such as lithium hydride, sodium hydride and potassium hydride. Hydride; lithium amide, sodium amide,
Alkali metal amides such as potassium amide; alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium propoxide, sodium butoxide, potassium-t-butoxide, sodium-t-pentoxide; lithium hexamethyldisilazide;
Alkali metal disilazides such as sodium hexamethyldisilazide, potassium hexamethyldisilazide; preferably alkali metal hydride, alkali metal alkoxide or alkali metal disilazide;
More preferably, they are sodium hydride, potassium hydride, potassium-t-butoxide, sodium-t-pentoxide, sodium hexamethyldisilazide, potassium hexamethyldisilazide or lithium hexamethyldisilazide, and particularly preferably. Is potassium hydride, potassium-
t-butoxide or lithium hexamethyldisilazide.

The reaction is suitably performed in the presence of a solvent. The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. For example, aliphatic or alicyclic hydrocarbons such as hexane and cyclohexane; benzene, toluene, xylene Aromatic ethers such as diethyl ether, tetrahydrofuran and dioxane; amides such as dimethylformamide and dimethylacetamide; sulfoxides such as dimethyl sulfoxide; and preferably aromatic hydrocarbons. , Ethers, amides or sulfoxides, more preferably aromatic hydrocarbons or ethers, particularly preferably ethers (particularly tetrahydrofuran).

The reaction temperature varies depending on the solvent, raw materials, reagents and the like, but is usually from -78 ° C to 100 ° C, preferably from -78 ° C to 0 ° C.

The reaction time varies depending on the solvent, starting materials, reagents, reaction temperature and the like, but is usually from 10 minutes to 24 hours, preferably from 30 minutes to 10 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 appropriately neutralized, and if insolubles are present, they are removed by filtration, and then an immiscible organic solvent such as water and ethyl acetate is added. It is obtained by separating and drying over anhydrous magnesium sulfate or the like, and then distilling off the solvent. If necessary, the obtained target compound can be further purified by a conventional method, for example, recrystallization, reprecipitation or chromatography.

Ninth Step Epoxidation Reaction by Deprotection This step is a step of producing a compound having the general formula (10), and removing the hydroxyl-protecting group of the compound having the general formula (9). Epoxidation is thereby achieved.

The deprotection reaction of the protecting group for the hydroxyl group can be carried out according to the sixth step.

Tenth Step Introduction Reaction of Protecting Group for Hydroxy Group This step is a step for producing a compound having the general formula (11), and is achieved by protecting the hydroxyl group of the compound having the general formula (10). Is done.

The introduction of the hydroxyl-protecting group can be carried out according to the first step.

Eleventh Step Lactonization Reaction by Deprotection This step is a step for producing a compound having the general formula (12).
Achieved by removing the ^4a group and lactonizing.

The reaction is performed in the presence of an acid. Examples of the acid used include trifluoroacetic acid, trichloroacetic acid,
Organic acids such as trifluoromethanesulfonic acid and formic acid, preferably formic acid.

The reaction is suitably performed in the presence of a solvent. The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, and is preferably a halogenated hydrocarbon such as methylene chloride, chloroform and dichloroethane.

The reaction temperature varies depending on the solvent, raw materials, reagents and the like, but is preferably from 0 ° C. to 50 ° C.

The reaction time varies depending on the solvent, raw materials, reagents, reaction temperature and the like, but is usually 1 to 48 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 appropriately neutralized. And an organic solvent that is immiscible, such as ethyl acetate, is added, washed with water, the organic layer containing the target compound is separated, dried over anhydrous magnesium sulfate or the like, and the solvent is distilled off. If necessary, the obtained target compound can be further purified by a conventional method, for example, recrystallization, reprecipitation or chromatography.

Step 12 Deprotection Reaction This step is a step for producing a compound having the general formula (13).
Achieved by removing the ^3a group.

The reaction is carried out by subjecting the compound having the general formula (12) to a hydrolysis reaction in the presence of a base or an acid.

The base to be used is not particularly limited as long as it is used as a base in a usual reaction. Preferably, alkali metal carbonates such as sodium carbonate, potassium carbonate and lithium carbonate; sodium hydroxide , Potassium hydroxide, barium hydroxide, alkali metal hydroxides or alkaline earth metal hydroxides such as lithium hydroxide;
Potassium hydroxide.

The reaction is suitably performed in the presence of a solvent. The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, and is preferably an alcohol such as methanol or ethanol; a mixed solvent of alcohol and water. The reaction temperature depends on the solvent, raw materials,
Although it varies depending on the reagent and the like, it is usually 0 ° C to 150 ° C, preferably 25 ° C to 100 ° C.

The reaction time varies depending on the solvent, raw materials, trial construction, reaction temperature and the like, but is usually 30 minutes to 24 hours, preferably 1 to 10 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 solution is acidified with an acid such as hydrochloric acid, extracted with an organic solvent not mixed with water such as ether, dried over anhydrous magnesium sulfate or the like, and then the solvent is distilled off to obtain the desired compound. Can be.

When the R ^3a group is a tertiary alkyl group (preferably a t-butyl group), an acid is used instead of a base. The acid used in the reaction is, for example, an organic acid such as trifluoroacetic acid, trichloroacetic acid, trifluoromethanesulfonic acid, and formic acid, and is preferably formic acid.

The reaction is suitably performed in the presence of a solvent. The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, and is preferably a halogenated hydrocarbon such as methylene chloride, chloroform and dichloroethane.

The reaction temperature varies depending on the solvent, raw materials, reagents and the like, but is preferably from 0 ° C. to 50 ° C.

The reaction time varies depending on the solvent, raw materials, trial construction, reaction temperature and the like, but is usually 1 to 48 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 insolubles are present, they are removed by filtration, an immiscible organic solvent such as water and ethyl acetate are added, and after washing with water, the organic layer containing the target compound is separated and dried over anhydrous magnesium sulfate or the like. Obtained by distilling off the solvent. If necessary, the obtained target compound can be further purified by a conventional method, for example, recrystallization, reprecipitation or chromatography.

Thirteenth Step Lactonization reaction by deprotection This step is a step of producing a compound having the general formula (13), and removing the protecting group R ^3a of the compound having the general formula (10). At the same time by removing the R ^4a group to form a lacton.

The protective group R ^{3a in} this step is removed, and
^The lactonization reaction by removing the ^4a group can be carried out according to the eleventh step and / or the twelfth step.

Fourteenth Step Condensation Reaction This step is a step for producing a compound having the general formula (15), and a compound having the general formula (13) and a compound having the general formula (14) (R ⁵ —NH—R ⁶ )
And condensed.

The reaction is carried out according to a conventional method for peptide synthesis, for example, an active ester method, a mixed acid anhydride method or a condensation method (preferably a condensation method).

1) The active ester method comprises the steps of:
The reaction is carried out by reacting the compound having the general formula (13) with an active esterifying agent to produce an active ester, and then reacting the compound with the compound having the general formula (14) in an inert solvent.

The active esterifying agent used is, for example, N
-Hydroxysuccinimide, 1-hydroxybenzotriazole or N-hydroxy-5-norbornene-
N-hydroxy compounds such as 2,3-dicarboximide; disulfide compounds such as dipyridyl disulfide; Further, the active esterification reaction is suitably performed in the presence of a condensing agent such as dicyclohexylcarbodiimide, carbonyldiimidazole or triphenylphosphine.

The solvent used in both reactions is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. For example, methylene chloride, chloroform,
Halogenated hydrocarbons such as carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane or diethylene glycol dimethyl ether; nitriles such as acetonitrile or isobutyronitrile And the like: formamide, dimethylformamide, dimethylacetamide, hexamethylphosphoramide (HMPA),
Amides such as hexamethylphosphorus triamide (HMPT); preferably ethers (particularly tetrahydrofuran), nitriles (particularly acetonitrile) or amides (particularly dimethylformamide).

The reaction temperature varies depending on the starting compounds, reagents and the like, but is usually from -20 ° C to 100 ° C, preferably from 0 ° C to 50 ° C for the active esterification reaction.
In the reaction between the active ester compound and the compound having the general formula (14), the reaction temperature is from -20 ° C to 100 ° C, preferably 0 ° C.
C. to 50C.

The reaction time varies depending on the starting compounds, the reagents and the reaction temperature.
4 hours, preferably 1 hour to 12 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, after the reaction is over,
The solvent was distilled off, or water was poured into the residue from which the solvent was distilled off, a water-immiscible solvent (eg, benzene, ether, ethyl acetate, etc.) was added to extract the target compound, and the extracted organic layer was washed with water. Thereafter, the target compound is obtained by drying using anhydrous magnesium sulfate or the like and distilling off the solvent. The obtained target compound can be obtained by a conventional method, if necessary.
For example, it can be further purified by recrystallization, reprecipitation, chromatography or the like.

2) In the mixed acid anhydride method, the compound having the general formula (13) is mixed with an acid anhydride in the presence or absence (preferably in the presence) of a base in an inert solvent. To produce a mixed acid anhydride, and then reacting the mixed acid anhydride with a compound having the general formula (14) in an inert solvent.

The mixed acid anhydride agents used are, for example, oxalyl halides such as oxalyl chloride; chloroformate C such as ethyl chloroformate and isobutyl chloroformate.
₁ -C ₅ esters; C _1, such as pivaloyl chloride
-C ₅ alkanoyl halide diethyl cyano phosphate,
C ₁ -C ₄ alkyl or di C ₆ -C ₁₄ aryl cyanophosphate such as diphenyl cyanophosphate; is, preferably a halogenated oxalyl (particularly oxalyl chloride). The reaction is carried out in the presence or absence of a base, but is preferably carried out in the presence of a base. The bases used are, for example, alkali metal carbonates such as sodium carbonate, potassium carbonate or lithium carbonate; triethylamine, tributylamine, diisopropylethylamine,
N-methylmorpholine, pyridine, 4- (N, N-dimethylamino) pyridine, N, N-dimethylaniline,
N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2.2.2] octane (DABCO), 1,8-diazabicyclo [5. 4.0] Undec-7-ene (DB
Organic amines such as U); and preferably organic amines (especially triethylamine).

The reaction for producing the mixed acid anhydride is suitably carried out in the presence of a solvent. The solvent to be used is not particularly limited as long as it can dissolve the starting materials to some extent. For example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; diethyl ether, diisopropyl Ethers such as ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; amides such as formamide, dimethylformamide, dimethylacetamide, hexamethylphosphoramide (HMPA), hexamethylphosphorous triamide (HMPT); And preferably halogenated hydrocarbons (dichloromethane).

The reaction temperature in the reaction for producing the mixed acid anhydride varies depending on the starting compounds, reagents and the like.
The temperature is from 50 ° C to 100 ° C, preferably from -10 ° C to 50 ° C.

The reaction time in the reaction for producing the mixed acid anhydride varies depending on the starting compounds, the reagents and the reaction temperature, but is usually from 5 minutes to 20 hours, preferably from 10 minutes to 10 hours.

The solvent used in the reaction between the mixed acid anhydride and the compound having the general formula (14) is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. For example, ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; formamide, dimethylformamide, dimethylacetamide, hexamethylphosphoramide (HMPA), hexamethylphosphorus triamide (H
Amides such as MPT), and preferably amides (particularly dimethylformamide).

The reaction temperature of the reaction between the mixed acid anhydride and the compound having the general formula (14) varies depending on the starting compounds, reagents and the like, but is usually -30 ° C to 100 ° C, preferably 0 ° C. ° C to 80 ° C.

The reaction time in the reaction between the mixed acid anhydride and the compound having the general formula (14) varies depending on the starting compound, the reagent and the reaction temperature, but is usually from 5 minutes to 24 hours.
Time, preferably 10 minutes to 12 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, after completion of the reaction, the solvent is distilled off, or water is poured into the residue from which the solvent is distilled off, and a water-immiscible solvent (eg, benzene, ether, ethyl acetate, etc.) is added to extract the target compound, and the extraction is performed. The obtained organic layer is washed with water, dried over anhydrous magnesium sulfate or the like, and the solvent is distilled off to obtain the desired compound. The obtained target compound can be further purified, if necessary, by a conventional method, for example, recrystallization, reprecipitation or chromatography.

3) Next, the condensation method is carried out by reacting the compound having the general formula (13) with the compound having the general formula (14) using a condensing agent and a base in an inert solvent. Will be

The condensing agent used is, for example, azodicarboxylic acid diester-lower alkyl ester triphenylphosphine such as triphenylphosphine; N, N'-dicyclohexylcarbodiimide (DCC) such as N, N'-dicyclohexylcarbodiimide (DCC). N-dicycloalkylcarbodiimides; 2-halo-1-lower alkylpyridinium halides such as 2-chloro-1-methylpyridinium iodide; diarylphosphoryl azides such as diphenylphosphoryl azide (DPPA); Chloroformates such as ethyl chloroformate and isobutyl chloroformate; phosphoryl chlorides such as diethylphosphoryl chloride; imidazole derivatives such as N, N'-carbodiimidazole (CDI);
Carbodiimide derivatives such as ethyl-3- (3-diethylaminopropyl) carbodiimide hydrochloride (EDAPC); sulfonyl chloride derivatives such as 2,4,6-triisopropylbenzenesulfonyl chloride; and preferably DDC and CDI. , 2-chloro-1-methylpyridinium iodide, isobutyl chloroformate, and diethylphosphoryl chloride.

As the base used, for example, triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4- (N, N
-Dimethylamino) pyridine, 4-pyrrolidinopyridine, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] nona-5
-Ene, 1,4-diazabicyclo [2.2.2] octane (DABCO), 1,8-diazabicyclo [5.4.
0] Organic bases such as undec-7-ene (DBU), preferably triethylamine, diisopropylethylamine, pyridine and 4-pyrrolidinopyridine.

The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Preferably, aromatic solvents such as benzene, toluene and xylene; dichloromethane, Chloroform,
Halogenated hydrocarbons such as dichloroethane; esters such as ethyl acetate and propyl acetate; ethers such as diethyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; ketones such as acetone and methyl ethyl ketone; Nitro compounds such as acetonitrile and isobutyronitrile; amides such as dimethylformamide, dimethylacetamide and hexamethylphosphorotriamide; more preferably, nitriles (particularly acetonitrile);
Aromatic hydrocarbons (especially benzene), halogenated hydrocarbons (especially dichloromethane) and ethers (especially tetrahydrofuran).

The reaction temperature varies depending on the solvent, raw materials, reagents and the like, but is usually 0 ° C. to 150 ° C., preferably 25 ° C.
° C to 120 ° C.

The reaction time varies depending on the solvent, starting materials, reagents, reaction temperature and the like, but is usually 10 minutes to 48 hours, preferably 1 to 24 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 obtained by adding a water-immiscible organic solvent such as ethyl acetate, washing with water, separating the organic layer containing the target compound, drying over anhydrous magnesium sulfate or the like, and distilling off the solvent. . If necessary, the obtained target compound can be obtained by a conventional method,
For example, it can be further purified by recrystallization, reprecipitation or chromatography.

Fifteenth Step Amidation reaction This step is a step for producing a compound having the general formula (17), and a compound having the general formula (12) and a compound having the general formula (16) (R ^7- NH ₂ ).

The reaction is suitably performed in the presence of a solvent. The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. For example, halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, and dichlorobenzene Ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether; nitriles such as acetonitrile and iributyronitrile; formamide, dimethylformamide, dimethylacetamide, hexamethylphosphoramide (HMPA) , Hexamethylphosphorustriamide (H
Amides such as MPT); alcohols such as methanol and ethanol; and preferably alcohols.

The reaction temperature varies depending on the solvent, starting compounds, reagents and the like, but is usually from -20 ° C to 100 ° C, preferably from 0 ° C to 50 ° C, and from -20 ° C to 100 ° C for the reaction with ammonia. And preferably between 0 ° C and 50 ° C.

The reaction time varies depending on the solvent, the starting compound, the reagent, the reaction temperature and the like, but is usually from 10 minutes to 24 hours, preferably from 30 minutes to 12 hours for both reactions.

After completion of the reaction, the target compound of this step is collected from the reaction mixture according to a conventional method. For example, after completion of the reaction, the solvent is distilled off, or water is poured into the residue obtained by distilling off the solvent, and a water-immiscible solvent (eg, benzene, ether, ethyl acetate, etc.) is added to extract the target compound. The extracted organic layer is washed with water, dried using anhydrous magnesium sulfate or the like, and the target compound is obtained by distilling off the solvent. The obtained target compound can be further purified, if necessary, by a conventional method, for example, recrystallization, reprecipitation or chromatography.

Step 16 Introduction Reaction of Protecting Group for Hydroxyl Group This step is a step for producing a compound having the general formula (18), and is achieved by protecting the hydroxyl group of the compound having the general formula (17). Is done.

The reaction of introducing a protecting group for a hydroxyl group (preferably a trialkylsilyl group) in this step can be carried out according to the first step.

Seventeenth Step Amidation Reaction This step is a step for producing a compound having the general formula (19), and a compound having the general formula (15) and a compound having the general formula (16) (R ^7- NH ₂ ).

The amidation reaction in this step can be carried out according to the fifteenth step.

Eighteenth Step Introduction Reaction of Protecting Group for Hydroxyl Group This step is a step for producing a compound having the general formula (20), and is achieved by protecting the hydroxyl group of the compound having the general formula (19). Is done.

The reaction of introducing a protecting group for a hydroxyl group (preferably a trialkylsilyl group) in this step can be carried out according to the first step.

Nineteenth Step Substitution Reaction This step is a step for producing a compound having the general formula (22), and a compound having the general formula (20) and a compound having the general formula (21) (X ² -A ¹ -CH ²
-OH).

In the reaction, a carbanion obtained by reacting a halide having the general formula (21) with a base is brought into contact with a compound having the general formula (20).

When a base is allowed to act on the halide having the general formula (21), examples of the base include alkyl lithium such as methyl lithium, butyl lithium, s-butyl lithium, and t-butyl lithium. , Preferably butyllithium, s-butyllithium and t-butyllithium, and more preferably t-butyllithium.

The reaction is preferably performed in the presence of a solvent.
The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. For example, aliphatic or alicyclic hydrocarbons such as hexane and cyclohexane; benzene, toluene, and xylene Such aromatic hydrocarbons; diethyl ether, tetrahydrofuran,
Ethers such as dioxane; amides such as dimethylformamide and dimethylacetamide; sulfoxides such as dimethylsulfoxide; preferably aromatic hydrocarbons, ethers and amides;
More preferred are aromatic hydrocarbons or ethers, and particularly preferred are ethers (particularly, tetrahydrofuran). This step is preferably performed under a stream of an inert gas such as nitrogen, helium, or argon.

The reaction temperature varies depending on the solvent, starting compounds, reagents and the like, but is usually from -78 ° C to 0 ° C, preferably from -78 ° C to -20 ° C.

The reaction time varies depending on the solvent, the starting compound, the reagent, the reaction temperature and the like, but is usually 30 minutes to 24 hours, preferably 30 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, after completion of the reaction, the reaction mixture is poured into a cooled aqueous solution of saturated ammonium chloride or the like, and a water-immiscible solvent (eg, benzene, ether, ethyl acetate, etc.) is added to extract the target compound, and the extracted organic layer is washed with water. After that, drying is performed using anhydrous magnesium sulfate or the like, and the solvent is distilled off to obtain the desired compound. The obtained target compound can be further purified, if necessary, by a conventional method, for example, recrystallization, reprecipitation or chromatography.

Twentieth Step Oxidation Reaction of Alcohol This step is a step for producing a compound having the general formula (23), and is achieved by oxidizing a compound having the general formula (22).

The oxidation reaction of the alcohol in this step can be carried out according to the fourth step.

Step 21 Deprotection of hydroxyl-protecting group This step is for producing a compound having the general formula (24), and removing the hydroxyl-protecting group of the compound having the general formula (22). Is achieved by doing

The reaction for removing the hydroxyl-protecting group in this step can be carried out according to the sixth step.

Twenty-second step Wittig
Reaction This step is a step for producing a compound having the general formula (27), and a compound having the general formula (23) and a Wittig reagent having the general formula (25) ((R ⁹ ) _{3
^{P + CH 2 (X 3)}} - R 8) or the general formula (Wittig having 26) - Horner Emon scan reagent ((R ⁹ O) ₂
(P (O) CH ₂ R ⁸ ).

The reaction is performed in the presence of a base. Examples of the base used include alkyl lithiums such as methyl lithium and butyl lithium; alkali metal hydrides such as sodium hydride and potassium hydride; alkali metal amides such as lithium amide, sodium amide and potassium amide; sodium Alkali metal alkoxides such as methoxide, sodium ethoxide, potassium propoxide, sodium butoxide, potassium-t-butoxide, sodium-t-pentoxide; lithium hexamethyldisilazide, sodium hexamethyldisilazide, potassium hexamethyldioxide Alkali metal disilazides such as silazide; preferably alkali metal hydrides, alkali metal alkoxides or alkali metal disilazides; more preferably potassium-t-butoxide; Lithium-t-pentoxide, sodium hexamethyldisilazide, potassium hexamethyldisilazide, and lithium hexamethyldisilazide; potassium-t-butoxide, potassium hexamethyldisilazide, and lithium hexamethyldisilazide are particularly preferred. It is silazide. In this reaction, a crown ether compound can be used. The crown ether compounds used are, for example, 12-crown-4, 15-crown-5, 18-crown-6, 1-aza-12-crown-4, 1-aza-15-crown-5, 1-aza -18-crown-
6, benzo-15-crown-5, 4'-nitrobenzo-15-crown-5, benzo-18-crown-6,
Dibenzo-18-crown-6, dibenzo-24-crown-8, dicyclohexano-18-crown-6, dicyclohexano-24-one crown-8, preferably 15-crown-5,18-crown -6, 1-aza
15-crown-5, 1-aza-18-crown-6,
Benzo-15-crown-5,4'-nitrobenzo-1
5-Crown-5, benzo-18-crown-6, dibenzo-18-crown-6 or dicyclohexano-1
8-crown-6, more preferably 15-crown-5, 18-one crown-6, 1-aza-18-crown-6, benzo-18-crown-6, dibenzo-18-
Crown-6 or dicyclohexano-18-crown-6, particularly preferably 18-crown-6.

The reaction is suitably performed in the presence of a solvent. As the solvent to be used, ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether (particularly, tetrahydrofuran) are preferable.

This reaction is preferably carried out under a stream of an inert gas such as nitrogen, helium, or argon.

The reaction temperature varies depending on the solvent, starting compounds, reagents and the like, but is preferably from -78 ° C to 0 ° C.

The reaction time varies depending on the solvent, starting compound, reagent, reaction temperature and the like, but is preferably from 10 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, after the reaction is completed, the reaction solution is poured into an aqueous ammonium chloride solution, extracted with a water-immiscible solvent such as benzene, ether, ethyl acetate, and the like, and the solvent is distilled off from the extract. The obtained target compound can be further purified, if necessary, by a conventional method, for example, recrystallization, reprecipitation or chromatography.

Twenty-third Step Deprotection reaction of hydroxyl-protecting group This step is a step of producing a compound having the general formula (28), and removing the hydroxyl-protecting group of the compound having the general formula (23). Is achieved by doing

The reaction for removing the hydroxyl-protecting group in this step can be carried out according to the sixth step.

Twenty-fourth Step Deprotection of hydroxyl-protecting group This step is a step of producing a compound having the general formula (29), and removing the hydroxyl-protecting group of the compound having the general formula (27). Is achieved by doing

The reaction for removing the hydroxyl-protecting group in this step can be carried out according to the sixth step.

Twenty-fifth Step Substitution Reaction This step is a step for producing a compound having the general formula (31), and a compound having the general formula (20) and a compound having the general formula (30) (X ⁴ -A ² ).

The substitution reaction in this step can be carried out according to the nineteenth step.

Twenty- Sixth Step The deprotection reaction of the protecting group for the hydroxyl group This step is a step of producing a compound having the general formula (32), and removing the hydroxyl protecting group of the compound having the general formula (31). Is achieved by doing

The reaction for removing the hydroxyl-protecting group in this step can be carried out according to the sixth step.

Step 27 Amidation Reaction This step is a step for producing a compound having the general formula (33), and a compound having the general formula (13) and a compound having the general formula (16) (R ^7- NH ₂ ).

The amidation reaction in this step can be carried out according to the fifteenth step.

Twenty-eighth Step Introduction Reaction of Protecting Group for Hydroxy Group This step is a step for producing a compound having the general formula (34), and is achieved by protecting the hydroxyl group of the compound having the general formula (33). Is done.

The introduction of a protecting group for a hydroxyl group (preferably a trialkylsilyl group) in this step can be carried out according to the first step.

Twenty- ninth Step S by opening the lactone ring
Etherification reaction This step is a step for preparing a compound having the general formula (36), the general formula (13) compound with a compound having the general formula (35) with a (R ^4b -OH) Achieved by contact.

The reaction is performed in the presence of a base. Examples of the base used include metals such as lithium, sodium, potassium and magnesium; and metal hydrides such as lithium hydride, sodium hydride, potassium hydride and calcium hydride. Preferably, they are sodium hydride and potassium hydride. This reaction is preferably carried out under a stream of an inert gas such as nitrogen, helium or argon.

The reaction is suitably performed in the presence of a solvent. The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. Examples thereof include ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether; Is raised. In addition, an excess of the alcohol compound used as a reagent can also be used as a solvent. Preferably, they are alcohols.

The reaction temperature varies depending on the solvent, starting compound, reagent and the like, but is preferably from -20 ° C to 70 ° C.
More preferably, it is 0 ° C to 50 ° C.

The reaction time varies depending on the solvent, starting compound, reagent, reaction temperature and the like, but is preferably from 10 minutes to 48 hours, more preferably from 30 minutes to 10 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, after the reaction is completed, the reaction solution is poured into an aqueous ammonium chloride solution, extracted with a water-immiscible solvent such as benzene, ether, ethyl acetate, and the like, and the solvent is distilled off from the extract. The obtained target compound can be further purified, if necessary, by a conventional method, for example, recrystallization, reprecipitation or chromatography.

Step 30 Introduction Reaction of Protecting Group for Hydroxy Group This step is a step for producing a compound having the general formula (37), and is achieved by protecting the hydroxyl group of the compound having the general formula (36). Is done.

The introduction of a hydroxyl-protecting group (preferably a trialkylsilyl group) in this step can be carried out according to the first step.

Step 31 S by opening the lactone ring
Etherification reaction This step is a step for preparing a compound having the general formula (38), the general formula (15) compound with a compound with the general formula (35) with a (R ^4a -OH) Achieved by contact.

The esterification reaction by ring-opening of the lactone ring in this step can be carried out according to the 29th step.

Thirty-second Process Introducing a Protecting Group for a Hydroxy Group This step is a process for producing a compound having the general formula (39), and is achieved by protecting the hydroxyl group of the compound having the general formula (38). Is done.

The introduction of a protecting group for a hydroxyl group (preferably a trialkylsilyl group) in this step can be carried out according to the first step.

Step 33 : Lactonization by hydrolysis
Response The present step is a step for preparing a compound having the general formula (40) is achieved by lactonization of a compound having the general formula (32).

The lactonization reaction in this step can be carried out according to the eleventh step.

Thirty-fourth Step S by opening the lactone ring
Etherification reaction This step is a step for preparing a compound having the general formula (41), the general formula (40) compound with a compound with the general formula (35) with a (R ^4a -OH) Achieved by contact.

The esterification reaction in this step can be carried out according to the 29th step.

Step 35 Introduction Reaction of Protecting Group for Hydroxy Group This step is a step for producing a compound having the general formula (42), and is achieved by protecting the hydroxyl group of the compound having the general formula (41). Is done.

The introduction of a protecting group for a hydroxyl group (preferably a trialkylsilyl group) in this step can be carried out according to the first step.

[0268]

Next, the present invention will be described in more detail with reference to examples and reference examples, but the present invention is not limited to these examples.

Example 1 3- (1-hydroxyethyl)
Oxirane-2,2-dicarboxylic acid di (t-butyl) ester
Ster (Exemplified Compound No. 1-6) The crude product of di (t-butyl) 2- (1,2-bistrimethylsilyloxypropyl) -2-iodomalonate obtained in Reference Example 6 was treated with tetrahydrofuran under a nitrogen stream. Dissolved in 100 ml and cooled to -45 ° C. Then, 25 ml (1.0 M, 25 mmol) of a tetrabutylammonium fluoride solution in tetrahydrofuran was added dropwise thereto, and the mixture was heated to -15 ° C and stirred for 1 hour. Water was added to the reaction mixture, the aqueous layer was extracted with ether, and the organic layer was washed with an aqueous solution of sodium thiosulfate and water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure.
The obtained residue was subjected to column chromatography (15 to 3).
Purification with 5% ethyl acetate-hexane) provided 1.35 g (46%) of the desired compound.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 19.4, 27.8, 61.0, 65.1, 65.9, 83.4, 84.0, 163.7, 1
64.6.

Example 2 4-Methyl-2-oxo-3,
6-dioxabicyclo [3.1.0] hexane-1-ca
Rubonic acid (exemplified compound number 2-1) Formic acid was added to 1.28 g (4.4 mmol) of 3- (1-hydroxyethyl) oxirane-2,2-dicarboxylic acid di (t-butyl) ester obtained in Example 1. Add 5 ml,
Stirred overnight. The target compound was obtained by removing formic acid from the reaction mixture under reduced pressure. The obtained target compound was used for the next reaction without purification.

1) ¹ H-NMR (270 MHz, CDC
l ₃ ) δ, ppm 1.50 (d, J = 6.5 Hz, 3 H), 4.45 (d, J = 1.2 Hz, 1
H), 4.76 (qd, J = 6.5 Hz, 1.2 Hz, 1 H).

Example 3 4-Methyl-2-oxo-3,
6-dioxabicyclo [3.1.0] hexane-1-ca
Rubonic acid methoxy-methylamide (Exemplary Compound No. 2
-14) 4-Methyl-2-oxo-3,6- obtained in Example 2.
The crude product of dioxabicyclo [3.1.0] hexane-1-carboxylic acid is dissolved in 20 ml of methylene chloride under a stream of nitrogen, and then N, O-dimethylhydroxylamine 6
44 mg (6.6 mmol) and 1.1 ml (6.2 mmol) of diisopropylethylamine were sequentially added, and the mixture was cooled with ice. Next, 1.28 g (6.2 mmol) of N, N′-dicyclohexylcarbodiimide was added thereto, and the mixture was stirred at 0 ° C. for 1 hour. After the reaction, water was added to the reaction mixture,
The solvent was distilled off under reduced pressure, then ethyl acetate was added, and the insolubles were filtered. The obtained filtrate was extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography (30-60% ethyl acetate-hexane) to give 293 mg (33%) of the desired compound.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 14.9, 32.2, 59.3, 61.3, 62.3, 74.9, 161.4, 167.2.

Example 4 3- (1-hydroxyethyl)
Oxirane-2,2-dicarboxylic acid amide methoxy-meth
Cylamide (Exemplified Compound No. 1-60) 4-Methyl-2-oxo- 3,6- obtained in Example 3
Dioxabicyclo [3.1.0] hexane-1-carboxylic acid methoxy-methylamide 100 mg (0.50 mm
ol) was dissolved in 1 ml of methanol, 4 ml of a methanol solution saturated with ammonia was added, and the mixture was stirred at room temperature for 30 minutes. After completion of the reaction, the solvent was distilled off from the reaction mixture under reduced pressure to obtain the target compound. The obtained target compound was used for the next reaction without purification.

1) ¹ H-NMR (270 MHz, CDC
l ₃ ) δ, ppm 1.34 (d, J = 6.5 Hz, 3 H), 3.25 (br.s, 3H), 3.56
(br.d, J = 8.4 Hz, 1 H), 3.79 (s, 3H), 3.75-3.85
(m, 1H), 5.76 (br. s, 1H), 6.43 (br. s, 1H).

Example 5 3- (1- (t-butyl dimethyl)
Lucylyloxy) ethyl) oxirane-2,2-dical
Bonamide methoxy-methylamide (Exemplified Compound No. 1-75) 3- (1-hydroxyethyl) oxirane-2,2-dicarboxylic acid amide methoxy-methylamide obtained in Example 4 and imidazole 136 2 mg (2.
0 mmol) was dissolved in 3 ml of N, N-dimethylformamide under a nitrogen stream and cooled with ice. Then, 150.7 mg (1.0 mm) of t-butylchlorodimethylsilane was added thereto.
ol), and the mixture was heated to room temperature and stirred for 1 hour. After completion of the reaction, a saturated aqueous solution of sodium hydrogen carbonate was added to the reaction mixture, the aqueous layer was extracted with ethyl acetate, the extract was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography (30-60% ethyl acetate-hexane) to give 155 mg (93%) of the desired compound.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 4.7, 4.5, 18.1, 20.3, 25.7, 32.4, 61.5, 62.1, 66.
7, 67.2, 165.2, 167.7.

Example 6 3- (1- (t-butyl dimethyl)
Lucylyloxy) ethyl) -2- (6-hydroxy-2
-Methyl-2-hexenoyl) oxirane-2-carbo
Acid amide (Exemplified Compound No. 1-107) 5-bromo-4-hexene-1- obtained in Reference Example 10
269 mg (1.5 mmol) of allol was dissolved in 5 ml of tetrahydrofuran under a nitrogen stream and cooled to -78 ° C. Next, 2.5 ml (1.64 M, 4.2 mmol) of a pentane solution of t-butyllithium was slowly added dropwise thereto, followed by stirring at -78 ° C for 20 minutes. 99 mg of 3- (1- (t-butyldimethylsilyloxy) ethyl) oxirane-2,2-dicarboxylic acid amide methoxy-methylamide obtained in Example 5 (0.3 mmol) was added to this solution.
1) A solution of 3 ml of tetrahydrofuran was added dropwise, and -78 was added.
Stirred at C for an additional hour. After completion of the reaction, a saturated aqueous solution of ammonium chloride was added to the reaction mixture, the aqueous layer was extracted with ethyl acetate, the extract was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography (40-70% ethyl acetate-hexane) to give 91.5 of the desired compound
mg (83%) were obtained.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 4.7, 4.5, 11.2, 18.0, 20.4, 25.7, 26.0, 31.2, 62.
1, 65.2, 66.9, 67.6, 135.3, 149.4, 167.1, 192.7.

Example 7 3- (1- (t-butyl dimethyl)
Lucylyloxy) ethyl) -2- (2-methyl-6-o
Oxo-2-hexenoyl) oxirane-2-carboxylic acid
Amide (Exemplified Compound No. 1-110) 3- (1- (t-butyldimethylsilyloxy) ethyl) -2- (6-hydroxy-2-methyl-2-hexenoyl) oxiran-2 obtained in Example 6 -51.1 mg (0.14 mmol) of carboxylic acid amide was dissolved in 1.5 ml of methylene chloride under a nitrogen stream, and 1,1,1-triacetoxy-1,1-dihydro-1,2-benzidoxol-3 was dissolved. (1H) -one 178.1 mg (0.42
mmol) and stirred at room temperature for 20 minutes. After completion of the reaction, an aqueous solution of sodium thiosulfate and an aqueous solution of saturated sodium hydrogen carbonate were sequentially added to the reaction mixture, the aqueous layer was extracted with ethyl acetate, the extract was washed with water, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. Was distilled off. The obtained residue was purified by column chromatography (30-50% ethyl acetate-hexane) to give the desired compound 4
1.0 mg (81%) was obtained.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 4.8, 4.5, 11.3, 18.0, 20.3, 21.8, 25.7, 42.2, 65.
1, 66.7, 67.5, 135.7, 146.8, 167.1, 192.6, 200.3
.

Example 8 11- (3- (1- (t-butyl)
Dimethylsilyloxy) ethyl) -2-carbamoyl
Oxiranyl) -2-ethylidene-4,10-dimethyl
Methyl 11-oxo-3,5,9-undecatrienoate
Glycol ester (Compound No. 1-113) tributyl obtained in Reference Example 15 - (4-methoxycarbonyl-2-methyl-2,4-hexadienyl) phosphonium bromide 179 mg (. 0 41 mmol) and 18-crown-6 / acetonitrile 125 mg (0.
41 mmol) in tetrahydrofuran 1m under a nitrogen stream
and cooled to -78 ° C. Then, 0.33 ml of potassium t-butoxide (1.0 M,
0.33 mmol) was added dropwise, and the temperature was raised to -45 ° C.
Stir for 5 minutes. The 3- (1-) obtained in Example 7 was
(T-butyldimethylsilyloxy) ethyl) -2-
(2-Methyl-6-oxo-2-hexenoyl) oxirane-2-carboxylic acid amide 30.1 mg (0.081
mmol) in 1 ml of tetrahydrofuran solution,
Stirred at -45 ° C for 10 minutes. After completion of the reaction, a saturated aqueous solution of sodium hydrogen carbonate was added to the reaction mixture, the aqueous layer was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography (10 to 25% ethyl acetate-hexane) to give 28.6 mg (69%) of the desired compound.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 4.7, 4.5, 11.3, 14.3, 15.8, 18.0, 20.4, 25.7, 28.
8, 31.4, 51.9, 65.1, 66.8, 67.5, 122.9, 128.4, 130.
4, 135.2, 135.5, 138.1, 139.8, 148.3,167.0, 167.8,
192.6.

Example 9 11- (2-carbamoyl-3
-(1-hydroxyethyl) oxiranyl) -2-ethyl
Riden-4,10-dimethyl-11-oxo-3,5
9- Undecatrienoic acid methyl ester (Exemplary Compound No. 1-196) 11- (3- (1- (t-butyldimethylsilyloxy) ethyl) -2-carbamoyloxiranyl)-obtained in Example 8 2-ethylidene-4,10-dimethyl-1
15.0 mg (0.030 mmol) of 1-oxo-3,5,9-undecatrienoic acid methyl ester was dissolved in 0.3 ml of tetrahydrofuran, 0.2 ml of triethylamine trihydrofluoride was added, and the mixture was stirred for 5 days.
After completion of the reaction, the solvent was distilled off from the reaction mixture under reduced pressure, and the residue was purified by column chromatography (60-80% ethyl acetate-hexane) to give the target compound 6.1.
mg (53%) were obtained.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 11.3, 14.3, 15.8, 19.3, 28.5, 31.3, 52.0, 65.6, 6
5.8, 66.2, 123.0, 128.2, 130.3, 135.0, 135.8, 138.
2, 140.0, 148.5, 166.9, 168.0, 192.7.

Example 10 3- (1- (t-butyldimethyl)
Tylsilyloxy) ethyl) -2-propionyloxy
Run-2-carboxylic acid amide (Exemplary Compound No. 1-9
3) 703 mg (2.1 m) of 3- (1- (t-butyldimethylsilyloxy) ethyl) oxirane-2,2-dicarboxylic acid amide methoxy-methylamide obtained in Example 5
mol) was dissolved in 10 ml of tetrahydrofuran under a stream of nitrogen, cooled to -45 ° C, and 5.0 ml of a solution of ethylmagnesium bromide in tetrahydrofuran (1.0 M,
5.0 mmol) was added dropwise, and the mixture was heated to 0 ° C and stirred for 3 hours. After completion of the reaction, a saturated aqueous solution of ammonium chloride was added to the reaction mixture, the aqueous layer was extracted with ethyl acetate, the extract was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography (5 to 10% ethyl acetate-hexane) to give 482 mg (76%) of the desired compound.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 4.8, 4.6, 7.2, 18.1, 20.2, 25.7, 31.9, 64.4, 66.9,
67.2, 165.8, 204.6.

Example 11 3- (1-hydroxyethyl)
B) -2-propionyloxirane-2-carboxylic acid
Mido (Exemplified Compound No. 1-176) As in Example 9, using 3- (1- (t-butyldimethylsilyloxy) ethyl) -2-propionyloxirane-2-carboxylic acid amide obtained in Example 10. The desired compound was obtained.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 7.5, 19.2, 32.3, 65.7, 67.1, 67.2, 168.7, 204.9.

Reference Example 1 2-Trityloxypropion
Acid methyl ester Methyl lactate (10.4 g, 100 mmol) and trityl chloride were dissolved in methylene chloride (500 ml) under a nitrogen stream, and 1,8-diazabicyclo [5.4.0] -7-undecene (19.4 ml, 130 mmol) was added dropwise. And stirred overnight at room temperature. After completion of the reaction, water was added to the reaction mixture, the aqueous layer was extracted with methylene chloride, the obtained extract was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography (6 to 10% ethyl acetate-hexane) to give 24.4 g (78%) of the desired compound.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 20.1, 51.3, 69.7, 127.2, 127.8, 129.0, 143.9, 173.
9.

Reference Example 2 2-Trityloxypropion
To 23.1 g (67 mmol) of 2-trityloxypropionic acid methyl ester obtained in Aldehyde Reference Example 1, 300 ml of hexane and 80 ml of methylene chloride were added under a nitrogen stream, and the mixture was cooled to -78 ° C. Then, 78 ml of a hexane solution of diisobutylaluminum hydride (0.95
M, 74 mmol) was added dropwise and stirred for 1 hour. After completion of the reaction, 32.2 sodium sulfate decahydrate was added to the reaction mixture.
g was added and the temperature was raised to room temperature. The solid was filtered off, and the solvent in the filtrate was distilled off under reduced pressure. The obtained residue was purified by column chromatography (5 to 8% ethyl acetate-hexane), and the obtained crystals were recrystallized from hexane to obtain 12.9 g (61%) of the desired compound. Was.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 17.3, 75.3, 87.8, 127.5, 128.1, 128.7, 143.9, 202.
6.

Reference Example 3 2- (1-hydroxy-2-to
(Richyloxypropyl) malonic acid di (t-butyl) s
Ether Reference Example 2 2-trityloxy propionaldehyde obtained in 35. 3mg (0. 11mmol) was dissolved in tetrahydrofuran 1ml under a stream of nitrogen, tetrahydrofuran solution in the presence of zinc chloride 0. 25ml (0. 5M,
0.12 mmol) and stirred at room temperature for 20 minutes.
Cooled to 78 ° C. To this, 0.045 ml (0.22 mmol) of malonic acid di (t-butyl) ester was dissolved in 1 ml of tetrahydrofuran under a nitrogen stream, cooled to -78 ° C, and then 0.20 ml of a solution of lithium hexamethyldisilazide in tetrahydrofuran. (1.0M, 0.20mm
ol) was added dropwise, and the solution stirred at -78 ° C for 20 minutes was added dropwise and stirred at -78 ° C for 15 minutes. After completion of the reaction, a saturated aqueous solution of ammonium chloride was added to the reaction mixture, the aqueous layer was extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography (5 to 10% ethyl acetate-hexane) to give 31.6 mg of the desired compound (51.6%).
3%).

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 17.5, 27.9, 55.2, 71.2, 73.2, 81.8, 82.0, 86.8, 12
7.1, 127.7, 128.9, 144.7, 167.1, 168.5.

Reference Example 4 2- (1,2-dihydroxyprop)
Ropyl) malonic acid di (t-butyl) ester 156 mg (0.29 mmol) of 2- (1-hydroxy-2-trityloxypropyl) malonic acid di (t-butyl) ester obtained in Reference Example 3 was placed under a nitrogen stream. After dissolving in 2 ml of methylene chloride with ice cooling, 0.045 ml (0.58 mmol) of trifluoroacetic acid was added dropwise, and the mixture was stirred at 0 ° C. for 20 minutes. After completion of the reaction, a saturated aqueous solution of sodium hydrogen carbonate was added to the reaction mixture, the aqueous layer was extracted with methylene chloride, the extract was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was subjected to column chromatography (15 to 40% ethyl acetate-
Hexane) to give 65.7m of the desired compound
g (77%) were obtained.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 19.4, 27.9, 55.9, 68.3, 74.2, 82.5, 82.8, 167.4, 1
68.5.

Reference Example 5 2- (1,2-bistrimethyl)
Silyloxypropyl) malonic acid di (t-butyl) s
54.4 mg of 2- (1,2-dihydroxypropyl) malonic acid di (t-butyl) ester obtained in Tell Reference Example 4
(0.19 mmol) and 74.9 mg of imidazole
(1.1 mmol) was dissolved in 2 ml of N, N-dimethylformamide under a stream of nitrogen, cooled with ice, added with 0.058 ml (0.48 mmol) of chlorotrimethylsilane, and stirred at 0 ° C. for 1 hour. After completion of the reaction, a saturated aqueous solution of sodium hydrogen carbonate was added to the reaction mixture, the aqueous layer was extracted with hexane, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue is subjected to column chromatography (0 to 2% ethyl acetate-hexane).
And purified to give 71.0 mg (87%) of the target compound.
%)was gotten.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 18.7, 28.0, 56.6, 69.7, 74.3, 81.1, 167.0, 167.2.

Reference Example 6 2- (1,2-bistrimethyl)
Di (t-silyloxypropyl) -2-iodomalonate
Butyl) ester 2 obtained in Reference Example 5 (1,2-bis-trimethylsilyloxy-propyl) malonate (t-butyl) ester 4. 42 g of (10 mmol) was dissolved in tetrahydrofuran 50ml under nitrogen flow, -23 ° C, and lithium hexamethyldisilazide in tetrahydrofuran solution 1
2 ml (1.0 M, 12 mmol) was added dropwise at -20 ° C.
For 1 hour. After cooling this to -45 ° C, 3.05 g (12 mmol) of iodine in tetrahydrofuran 1
0 ml of the solution was added dropwise, and the mixture was stirred at -20 ° C for 1 hour. After the completion of the reaction, a saturated aqueous solution of ammonium chloride was added to the reaction mixture, an aqueous solution of sodium thiosulfate was further added, the aqueous layer was extracted with hexane, and the extract was washed with an aqueous solution of sodium thiosulfate and water, and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure to obtain the target compound. This was used for the next reaction without purification.

1) ¹ H-NMR (270 MHz, CDC
l ₃ ) δ, ppm 0.14 (s, 9H), 0.18 (s, 9H), 1.17 (d, J = 6.3 Hz, 3
H), 1.46 (s, 9H), 1.47 (s, 9 H), 3.86 (d, J = 3.0
Hz, 1 H), 4.28 (qd, J = 6.3 Hz, 3.0 Hz, 1 H).

Reference Example 7 2- (3-bromo-2-buteni)
Lu) Malonic acid diethyl ester Tetrahedron lett. , 1978, 1
4.53 g (30 mmol) of 3-bromo-2-buten-1-ol obtained according to the method of 9,1051 was dissolved in 100 ml of tetrahydrofuran, and triethylamine was added to the residue.
4 ml (39 mmol) was added and the mixture was ice-cooled. Then, 2.8 ml of methanesulfonic acid chloride (36 mmol) was added thereto.
1) was added dropwise, and the mixture was stirred at 0 ° C. for 30 minutes, and the generated crystals were separated by filtration to obtain a filtrate. 2.62 g of sodium hydride
(55%, 60 mmol) were suspended in 150 ml of tetrahydrofuran under a nitrogen stream, 9.7 ml (60 mmol) of diethyl malonate was added dropwise under ice cooling, and the mixture was stirred at 0 ° C. for 10 minutes. At 0 ° C slowly
Stirred at C for 2 hours. After completion of the reaction, a saturated aqueous solution of ammonium chloride was added to the reaction mixture, the aqueous layer was extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography (5 to 10% ethyl acetate-hexane) to give the desired compound.

1) ¹ H-NMR (270 MHz, CDC
l ₃ ) δ, ppm 1.23-1.31 (m, 6H), 2.25 (s, 3H), 2.61 (dd, J = 7.6
Hz, 7.2 Hz, 2 H), 3.37 (t, J = 7.6 Hz, 1 H), 4.21
(q, J = 7.2 Hz, 4 H), 5.81 (t, J = 8.3 Hz, 1 H).

Reference Example 8 2- (3-bromo-2-buteni)
Ru) 2- (3-bromo-2-butenyl) obtained in malonic acid reference example 7
Malonic acid diethyl ester was dissolved in ethanol (80 ml), 1N aqueous sodium hydroxide solution (80 ml) was added, and the mixture was stirred at room temperature overnight. After completion of the reaction, the reaction mixture was neutralized by adding a 1N aqueous hydrochloric acid solution, the solvent was distilled off under reduced pressure, the aqueous layer was extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. Then, the target compound was obtained. This was used for the next reaction without purification.

1) ¹ H-NMR (270 MHz, CDC
l ₃ ) δ, ppm 2.27 (s, 3H), 2.67 (dd, J = 7.8 Hz, 7.0 Hz, 2 H),
3.51 (t, J = 7.8 Hz, 1 H), 5.85 (t, J = 7.0 Hz, 1
H), 6.46 (br. S, 2H).

Reference Example 9 5-bromo-4-hexenoic acid
2- (3-Bromo-2-butenyl) obtained in chill ester Reference Example 8
The crude product of malonic acid was converted to N, N-dimethylformamide 1
The mixture was dissolved in 00 ml and stirred at 100 ° C. for 2 hours. This was cooled to room temperature and 6.22 g (45 mmo) of potassium carbonate was added.
l) and 2.4 ml (39 mmol) of methyl iodide were added, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, water was added to the reaction mixture, the aqueous layer was extracted with ether, the extract was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography (5 to 10% ethyl acetate-hexane) to give 3.14 g (51%) of the desired compound.

1) ¹ H-NMR (270 MHz, CDC
l ₃ ) δ, ppm 2.24 (s, 3H), 2.29-2.43 (m, 4 H), 3.69 (s, 3 H), 5.
82 (t, J = 6.3 Hz, 1 H).

Reference Example 10 5-bromo-4-hexene-
3.13 g (15 mmol) of 5-bromo-4-hexenoic acid methyl ester obtained in 1-ole Reference Example 9 was dissolved in 50 ml of tetrahydrofuran under a nitrogen stream and cooled to -78 ° C. Then, this was added to lithium aluminum hydride 1.1.
4 g (30 mmol) was added and stirred for 30 minutes. After completion of the reaction, 1.1 ml of water, 1.1 ml of a 15% aqueous sodium hydroxide solution and 3.4 ml of water were added to the reaction mixture, 50 ml of tetrahydrofuran was added, the mixture was stirred for 30 minutes, and the solution was filtered using Hyfloss-Parcel. Then, the solvent of the filtrate was distilled off under reduced pressure. The obtained residue was purified by column chromatography (10 to 25% ethyl acetate-hexane) to give 2.40 g (89%) of the desired compound.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 23.1, 25.9, 31.8, 61.9, 119.8, 130.4.

Reference Example 11 t-Butyl- (3-iodo-
2-methylallyloxy) diphenylsilane Chem. Soc. Parkin Trans
3-Iodo-2 obtained according to the method of
-Methyl-2-propen-1-ol 7.06 g (36
mmol) and 7.28 g of imidazole (107 mmol)
l) in a nitrogen stream under N, N-dimethylformamide 10
0 ml, and t-butylchlorodiphenylsilane 1
0 ml (39 mmol) was added, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, a saturated aqueous solution of sodium hydrogen carbonate was added to the reaction mixture, the aqueous layer was extracted with ether, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure.
The obtained residue was purified by column chromatography (3% ethyl acetate-hexane) to give the title compound 1
4.9 g (96%) were obtained.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 19.3, 21.2, 26.8, 67.6, 76.0, 127.8, 129.8, 133.1,
135.5, 146.4.

Reference Example 12 5- (t-butyldiphenyl)
Silyloxy) -2-ethylidene-4-methyl-3-pe
T -butyl- (3-iodo-2-) obtained in Reference Example 11
2.18 g of methyl allyloxy) diphenylsilane
(5.0 mmol) was dissolved in 50 ml of tetrahydrofuran under a nitrogen stream and cooled to -78 ° C. Then, 7.6 ml of a pentane solution of t-butyllithium (1.
64M, 12.5 mmol) was slowly added dropwise and -78.
After stirring at 10 ° C for 10 minutes, 10 ml (10 mmol) of a solution of tributyltin chloride in tetrahydrofuran was added, and -78
Stirred at C for an additional 20 minutes. After completion of the reaction, a saturated aqueous solution of ammonium chloride was added to the reaction mixture, the aqueous layer was extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was dissolved in toluene under a nitrogen stream, Am. Chem. Soc. , 1
895 mg (5.0 mmol) of methyl 2-bromo-2-butenoate obtained according to the method of 990, 112, 5085.
And tetrakistriphenylphosphine palladium 5
78 mg (0.50 mmol) was added, and the mixture was heated under reflux overnight. After completion of the reaction, the solvent of the reaction solution was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (3 to 5% ethyl acetate-hexane) to give 961 mg (47%) of the desired compound. Obtained.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 15.2, 15.5, 19.3, 26.8, 51.7, 68.1, 117.0, 127.6,
129.6, 130.4, 133.7, 135.5, 139.0, 139.5, 168.1.

Reference Example 13 2-ethylidene-5-hydro
Xy-4-methyl-3 -pentenoic acid methyl ester 1.33 g of 5- (t-butyldiphenylsilyloxy) -2-ethylidene-4-methyl-3-pentenoic acid methyl ester obtained in Reference Example 12 (3.3. 2 mmol) was dissolved in 20 ml of tetrahydrofuran under a nitrogen stream, and 3.6 ml (1.0 M, 3.6 mmol) of a solution of tetrabutylammonium fluoride in tetrahydrofuran was added dropwise under ice cooling, and the mixture was heated to room temperature and stirred for 3 hours. . After completion of the reaction, water was added to the reaction mixture, the aqueous layer was extracted with ethyl acetate, the extract was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography (15-30% ethyl acetate-hexane) to give 473 mg (86%) of the desired compound.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 15.3, 15.6, 51.8, 67.8, 117.9, 130.0, 139.6, 140.
5, 167.9.

Reference Example 14 5-Bromo-2-ethylidene
-4-Methyl-3-pentenoic acid methyl ester 2-ethylidene-5-hydroxy-4-methyl-3-pentenoic acid methyl ester 264 obtained in Reference Example 13.
3 mg (1.6 mmol) was dissolved in 10 ml of tetrahydrofuran under a nitrogen stream, and triphenylphosphine 81 was dissolved.
After adding 3 mg (3.1 mmol) and cooling with ice, add 1.03 g (3.1 mmol) of carbon tetrabromide, and add
Stirred for minutes. After completion of the reaction, the solvent of the reaction solution was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (0 to 3% ethyl acetate-hexane) to give 343 mg (95%) of the desired compound. Obtained.

1) ¹ H-NMR (270 MHz, CDC
l ₃ ) δ, ppm 1.69 (d, J = 1.2 Hz, 3 H), 1.75 (dd, J = 7.3 Hz,
1.3 Hz, 3 H), 3.74 (s, 3 H), 4.07 (s, 2 H), 6.17 (b
rs, 1 H), 6.99 (q, J = 7.3 Hz, 1 H).

Reference Example 15 Tributyl- (4-methoxy)
Carbonyl-2-methyl-2,4-hexadienyl) e
5-Bromo-2-ethylidene-4 obtained in Suphonium Bromide Reference Example 14
-Methyl-3-pentenoic acid methyl ester 132 mg
(0.57 mmol) was dissolved in 4 ml of acetonitrile, and 0.18 ml (0.74 mm) of tributylphosphine was dissolved.
ol) and heated to reflux for 20 minutes. After completion of the reaction, the solvent of the reaction solution was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (0 to 2% methanol-chloroform) to obtain 249 mg of the desired compound (q
ant) was obtained.

1) ¹³ C-NMR (67.5 MHz, CD
Cl ₃ ) δ, ppm 13.4, 15.8, 19.2 (d, J = 46.2 Hz), 20.4, 23.9, 24.
1,29.3 (d, J = 44.6 Hz), 51.9, 126.8, 127.0, 129.
0, 141.3, 166.7.

Reference Example 16 2-ethylidene-11- (4
-Hydroxy-4-methyl-2-oxo-6-oxa-
3-azabicyclo [3.1.0] -1-hexyl-4,
10-dimethyl-11-oxo-3,5,9-undeca
Trienoic acid methyl ester (epolactaene) 11- (2-carbamoyl-3-) obtained in Example 9
(1-hydroxyethyl) oxiranyl) -2-ethylidene-4,10-dimethyl-11-oxo-3,5,9
-Undecatrienoic acid methyl ester 6.1 mg (0.1 mg)
016 mmol) in a stream of nitrogen under 0.5 m of methylene chloride.
1,1,1-triacetoxy-1,1-dihydro-1,2-benzidoxol-3 (1H)-
66.2 mg (0.078 mmol) of ON was added, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, an aqueous solution of sodium thiosulfate and an aqueous solution of saturated sodium hydrogen carbonate were sequentially added to the reaction mixture, the aqueous layer was extracted with ethyl acetate, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography (40-60% ethyl acetate-hexane) to give 4.5 mg (74%) of the desired compound.

1) ¹³ C-NMR (67.5 MHz, CD
₃ OD) δ, ppm 11.2, 14.6, 16.0, 22.2, 30.2, 32.5, 52.4, 64.0, 6
6.1, 84.8, 123.6, 129.7, 131.9, 136.6, 137.3, 139.
6, 140.9, 150.1, 169.5, 172.2, 192.1.

[0323]

The compounds having the above general formula (I) of the present invention are useful as intermediates for synthesizing various compounds.

Claims (48)

[Claims] 1. A compound of the general formula [In the formula, R ¹ is a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxyalkyl group having 2 to 12 carbon atoms in total, or A linear or branched hydroxyalkyl group having 1 to 6 carbon atoms, R ² represents a hydrogen atom or a hydroxyl-protecting group, and R ³ has 1 to 3 substituted α. A straight-chain or branched hydrocarbon group having 1 to 15 carbon atoms which may further have 1 to 5 double bonds, and a straight-chain hydrocarbon group having 1 to 6 carbon atoms Jo or branched alkoxy group, hydroxy group or formula -N (R ⁵⁾
A group having (R ⁶ ) (provided that R ⁵ is a linear or branched alkyl group having 1 to 6 carbon atoms or a linear or branched alkyl group having 1 to 6 carbon atoms) R ⁶ represents a linear or branched alkyl group having 1 to 6 carbon atoms), and R ⁴ represents a linear or branched alkyl group having 1 to 6 carbon atoms. A branched alkoxy group or a group having the formula —NH (R ⁷ ) (provided that R ⁷ represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms). Or R ² and R ⁴ are bonded together to form a single bond. The substituted α is hydroxy, formyl, carbon number 2
A straight-chain or branched alkoxycarbonyl or halogen having from 7 to 7; Or a salt thereof. 2. The epoxyethane derivative according to claim 1, wherein R ¹ is a linear or branched alkyl group having 1 to 4 carbon atoms, or a salt thereof. 3. The epoxyethane derivative or a salt thereof according to claim 1, wherein R ¹ is an alkyl group having 1 or 2 carbon atoms. 4. The epoxyethane derivative or a salt thereof according to claim 1, wherein R ¹ is a methyl group. 5. The method according to claim 1, wherein R ¹ is a straight-chain or branched alkoxy having 1 to 4 carbon atoms and a straight-chain or branched alkoxy having 1 to 4 carbon atoms. An epoxyethane derivative or a salt thereof, which is an alkoxyalkyl group consisting of: 6. An epoxyethane derivative or a salt thereof according to claim 1, wherein R ¹ is an alkoxyalkyl group comprising an alkoxy having 1 or 2 carbons and an alkyl having 1 or 2 carbons. 7. An epoxyethane derivative or a salt thereof according to claim 1, wherein R ¹ is a straight-chain or branched hydroxyalkyl group having 1 to 4 carbon atoms. 8. The epoxyethane derivative or a salt thereof according to claim 1, wherein R ¹ is a hydroxyalkyl group having 1 or 2 carbon atoms. 9. An epoxyethane derivative or a salt thereof according to one of claims 1 to 8, wherein R ² is a hydrogen atom. 10. An epoxyethane derivative or a salt thereof according to one of claims 1 to 8, wherein R ² is a hydroxyl-protecting group. 11. The method according to claim 1, wherein R ³ is an unsubstituted linear or branched alkyl group having 5 to 14 carbon atoms. An epoxyethane derivative or a salt thereof. 12. The method according to claim 1, wherein R ³ is an unsubstituted linear or branched alkyl group having 10 to 14 carbon atoms. An epoxyethane derivative or a salt thereof. 13. The method according to claim 1, wherein R ³ is a straight-chain or branched-chain having 5 to 14 carbon atoms having hydroxy as a substituent. An epoxyethane derivative or a salt thereof, which is an alkyl group. 14. The method according to claim 1, wherein R ³ is a straight or branched chain having 5 to 7 carbon atoms having hydroxy as a substituent. An epoxyethane derivative or a salt thereof, which is an alkyl group. 15. The method according to claim 1, wherein R ³ is a straight or branched chain having 4 to 13 carbon atoms having formyl as a substituent. An epoxyethane derivative or a salt thereof, which is an alkyl group. 16. A method according to claim 1, wherein R ³ is a straight or branched chain having 4 to 6 carbon atoms having formyl as a substituent. An epoxyethane derivative or a salt thereof, which is an alkyl group. 17. The method according to claim 1, wherein R ³ is substituted with 2 carbon atoms.
An epoxyethane derivative or a salt thereof, which is a linear or branched alkyl group having 5 to 14 carbon atoms and having a linear or branched alkoxycarbonyl group having 5 to 5 carbon atoms. 18. The method according to claim 1, wherein R ³ is substituted with 2 carbon atoms.
Or an epoxyethane derivative or a salt thereof, which is a linear or branched alkyl group having 5 to 7 carbon atoms having 3 alkoxycarbonyl groups. 19. The method according to claim 1, wherein R ³ is chloro,
An epoxyethane derivative or a salt thereof, which is a linear or branched alkyl group having 5 to 14 carbon atoms having bromo or iodo. 20. A linear or branched chain having 5 to 7 carbon atoms, wherein R ³ has chloro or bromo as a substituent, according to claim 1 selected from [1] to [10]. An epoxyethane derivative or a salt thereof, which is an alkyl group. 21. The method according to claim 1, wherein R ³ is an unsubstituted double bond.
An epoxyethane derivative or a salt thereof, which is a straight-chain or branched-chain hydrocarbon group having 5 to 4 carbon atoms and having 5 to 14 carbon atoms. 22. The method according to claim 1, wherein R ³ is an unsubstituted double bond.
Or an epoxyethane derivative or a salt thereof, which is a linear or branched hydrocarbon group having 2 and 5 to 7 carbon atoms. 23. The method according to claim 1, wherein R ³ has hydroxy as a substituent, has 1 to 4 double bonds, and has 5 to 5 carbon atoms. An epoxyethane derivative or a salt thereof, which is a linear or branched hydrocarbon group having 14 groups. 24. The method according to claim 1, wherein R ³ has hydroxy as a substituent, has 1 or 2 double bonds, and has 5 to 5 carbon atoms. An epoxyethane derivative or a salt thereof, which is a linear or branched hydrocarbon group having seven. 25. The method according to claim 1, wherein R ³ has formyl as a substituent, has 1 to 4 double bonds, and has 4 to 4 carbon atoms. An epoxyethane derivative or a salt thereof, which is a linear or branched hydrocarbon group having 13 groups. 26. The method according to claim 1, wherein R ³ has formyl as a substituent, has 1 or 2 double bonds, and has 4 to 4 carbon atoms. An epoxyethane derivative or a salt thereof, which is a linear or branched hydrocarbon group having six. 27. The method according to claim 1, wherein R ³ is substituted with 2 carbon atoms.
A straight-chain or branched-chain hydrocarbon having 1 to 4 double bonds and having 5 to 14 carbon atoms, having a straight-chain or branched alkoxycarbonyl having from 5 to 5 carbon atoms An epoxyethane derivative or a salt thereof. 28. The method according to claim 1, wherein R ³ is substituted with 2 carbon atoms.
Or an epoxyethane derivative or a salt thereof, which is a straight-chain or branched hydrocarbon group having 3 or 4 double bonds, having 3 or 4 double bonds, and having 12 to 14 carbon atoms. . 29. The method according to claim 1, wherein R ³ is chloro,
An epoxyethane derivative or a salt thereof, which is a linear or branched hydrocarbon group having 1 to 4 double bonds, having 5 to 14 carbon atoms, having bromo or iodo. 30. The method according to claim 1, wherein R ³ has chloro or bromo as a substituent, has one or two double bonds, and has at least one carbon atom. An epoxyethane derivative or a salt thereof which is a linear or branched hydrocarbon group having 5 to 7 carbon atoms. 31. The epoxy ethane according to claim 1, wherein R ³ is a linear or branched alkoxy group having 1 to 4 carbon atoms. Derivatives or salts thereof. 32. The epoxy ethane according to claim 1, wherein R ³ is a linear or branched alkoxy group having 3 or 4 carbon atoms. Derivatives or salts thereof. 33. An epoxyethane derivative or a salt thereof according to one of claims 1 to 10, wherein R ³ is a hydroxy group. 34. The method according to claim 1, wherein R ³ is a group selected from the group consisting of a group represented by the formula -N (R ^5a )
A group having (R ^6a ) (where R ^5a is a linear or branched alkyl group having 1 to 4 carbon atoms or a linear or branched alkyl group having 1 to 4 carbon atoms) R ^6a represents a linear or branched alkyl group having 1 to 4 carbon atoms), or a salt thereof. 35. The method according to claim 1, wherein R ³ is a compound of the formula —N (R ^5b )
A group having (R ^6b ) (provided that R ^5b has 1 or 2 carbon atoms)
An alkyl group having 1 or 2 or an alkoxy group having 1 or 2 carbon atoms. R ^6b represents an alkyl group having 1 or 2 carbon atoms. ) Or a salt thereof. 36. The epoxy ethane according to claim 1, wherein R ⁴ is a linear or branched alkoxy group having 1 to 4 carbon atoms. Derivatives or salts thereof. 37. The epoxy ethane according to claim 1, wherein R ⁴ is a linear or branched alkoxy group having 3 or 4 carbon atoms. Derivatives or salts thereof. 38. The method according to claim 1, wherein R ⁴ is a group having the formula —NH (R ^7a ) (where R ^7a is a hydrogen atom or a group having 1 to 4 carbon atoms). 4
Represents a linear or branched alkyl group having a single bond. ) Or a salt thereof. 39. The method according to claim 1, wherein R ⁴ is a group having the formula —NH (R ^7b ), provided that R ^7b is a hydrogen atom or a group having 1 or more carbon atoms. An epoxy ethane derivative or a salt thereof. 40. The method according to claim 1, wherein R ⁴ is a group having the formula —NH (R ^7c ) (where R ^7c represents a hydrogen atom). An epoxyethane derivative or a salt thereof. 41. One selected from [Claim 1] to [Claim 8] and [Claim 11] to [Claim 35]
In the item, an epoxyethane derivative or a salt thereof, wherein R ² and R ⁴ are bonded together to show a single bond. 42. The method according to claim 1, wherein the substituent α is hydroxy, formyl, or a linear or branched alkoxy having 2 to 7 carbon atoms. An epoxyethane derivative or a salt thereof which is carbonyl. 43. The method according to claim 1, wherein the substituted α is hydroxy, formyl, or a linear or branched alkoxy having 2 to 5 carbon atoms. An epoxyethane derivative or a salt thereof which is carbonyl. 44. The method according to claim 1, wherein the substituent α is hydroxy, formyl, or a linear or branched alkoxy having 2 or 3 carbon atoms. An epoxyethane derivative or a salt thereof which is carbonyl. 45. R ¹ is a linear or branched alkyl group having 1 to 4 carbon atoms, a linear or branched alkoxy group having 1 to 4 carbon atoms and 1 carbon atom. to a straight-chain or branched alkoxyalkyl group or C 1 -C consisting of alkyl straight-chain or branched hydroxyalkyl group having 4 having four; R ² is a hydrogen atom R ³ is an unsubstituted linear or branched alkyl group having 5 to 14 carbon atoms, a linear group having 5 to 14 carbon atoms having hydroxy as a substituent. Linear or branched alkyl group having 4 to 13 carbon atoms having formyl as a substituent, and 2 to 5 carbon atoms as a substituent.
Linear or branched alkylcarbonyl having 5 to 14 carbon atoms having a linear or branched alkoxycarbonyl having 5 or more carbon atoms having 5 to 14 carbon atoms having a chloro, bromo or iodo substituent. A straight-chain or branched-chain alkyl group having 14 carbon atoms, a straight-chain or branched-chain hydrocarbon group having 1 to 4 unsubstituted double bonds and 5 to 14 carbon atoms A straight-chain or branched hydrocarbon group having 1 to 4 double bonds and 5 to 14 carbon atoms having hydroxy as a substituent, formyl as a substituent, A linear or branched hydrocarbon group having 1 to 4 heavy bonds and 4 to 13 carbon atoms, a linear or branched hydrocarbon group having 2 to 5 carbon atoms as a substituent Having an alkoxycarbonyl A straight-chain or branched hydrocarbon group having 1 to 4 double bonds and 5 to 14 carbon atoms, chloro, bromo or iodo as a substituent, and 1 to 2 double bonds. Has 4 carbon atoms, 5 to 1
A linear or branched hydrocarbon group having 4 carbon atoms, a linear or branched alkoxy group having 1 to 4 carbon atoms, a hydroxy group, or a compound of the formula -N ( ^R5a )
A group having (R ^6a ) (where R ^5a is a linear or branched alkyl group having 1 to 4 carbon atoms or a linear or branched alkyl group having 1 to 4 carbon atoms) .R ^6a showing the alkoxy group is a straight or branched alkyl group having 1 to 4 carbon atoms be);. R ⁴ is a linear or amount having 1 to 4 carbon atoms A branched alkoxy group or a group having the formula —NH (R ^7a ) (provided that R ^7a is a hydrogen atom or a C 1 to C 4
Represents a linear or branched alkyl group having a single bond. Or R ² and R ⁴ are bonded together to form a single bond; an epoxyethane derivative or a salt thereof. 46. R ¹ is a straight-chain or branched alkyl group having 1 to 4 carbon atoms or a straight-chain or branched hydroxyalkyl group having 1 to 4 carbon atoms. R ² is a hydrogen atom or a protecting group for a hydroxyl group; R ³ is an unsubstituted linear or branched alkyl group having 5 to 14 carbon atoms, having hydroxy as a substituent, Having 1 to 4 bonds and 5 carbon atoms
A straight-chain or branched-chain hydrocarbon group having 1 to 14 carbon atoms, a formyl as a substituent, 1 to 4 double bonds and 4 to 13 carbon atoms. It has a branched hydrocarbon group, a linear or branched alkoxycarbonyl group having 2 to 5 carbon atoms as a substituent, has 1 to 4 double bonds, and has 5 to 14 carbon atoms. Or a straight-chain or branched-chain hydrocarbon group having 1 to 4 carbon atoms, a straight-chain or branched-chain alkoxy group having 1 to 4 carbon atoms, a hydroxy group, or a compound of the formula -N
(R ^5a ) a group having (R ^6a ) (where R ^5a is a linear or branched alkyl group having 1 to 4 carbon atoms or a linear or branched alkyl group having 1 to 4 carbon atoms) .R ^6a showing a branched chain alkoxy group is a straight or branched alkyl group having 1 to 4 carbon atoms be);. straight R ⁴ is having 1 to 4 carbon atoms A chain or branched alkoxy group or a formula -NH
(R ^7a) groups having a (wherein, R ^7a is from 1 number hydrogen atom or a C a linear or branched alkyl radical having 4 carbon atoms.) In there; or, R ² and R ⁴ Linked together to form a single bond; an epoxyethane derivative or a salt thereof. 47. An alkyl group having 1 or 2 carbon atoms, an alkoxyalkyl group consisting of an alkoxy having 1 or 2 carbon atoms and an alkyl having 1 or 2 carbon atoms, or R ¹ having 1 or 2 carbon atoms. R ² is a hydrogen atom or a protecting group for a hydroxyl group; R ³ is an unsubstituted linear or branched alkyl group having 10 to 14 carbon atoms;
A straight-chain or branched alkyl group having 5 to 7 carbon atoms having hydroxy as a substituent, and a straight-chain or branched alkyl group having 4 to 6 carbon atoms having formyl as a substituent. A straight-chain or branched alkyl group having 5 to 7 carbon atoms having an alkoxycarbonyl group having 2 or 3 carbon atoms as a substituent, and 5 to 7 carbon atoms having a chloro or bromo group as a substituent. Linear or branched alkyl group having one or two unsubstituted double bonds,
A straight-chain or branched hydrocarbon group having 5 to 7 carbon atoms, a straight-chain having 5 to 7 carbon atoms, having hydroxy as a substituent, 1 or 2 double bonds, Or branched hydrocarbon group, having formyl as a substituent, having one or two double bonds, and having 4 carbon atoms.
A straight-chain or branched hydrocarbon group having 6 to 6 carbon atoms, an alkoxycarbonyl having 2 or 3 carbon atoms as a substituent, having 3 or 4 double bonds, and having 12 to 12 carbon atoms. A straight-chain or branched-chain hydrocarbon group having 14 carbon atoms, chloro or bromo as a substituent, 1 or 2 double bonds and 5 to 7 carbon atoms; A branched hydrocarbon group, a linear or branched alkoxy group having 3 or 4 carbon atoms, a hydroxy group, or a compound of the formula -N
A group having (R ^5b ) (R ^6b ) (provided that R ^5b represents an alkyl group having 1 or 2 carbon atoms or an alkoxy group having 1 or 2 carbon atoms. R ^6b represents 1 or 2 carbon atoms) Wherein R ⁴ is a linear or branched alkoxy group having 3 or 4 carbon atoms or a group having the formula —NH (R ^7b ), provided that R ^7b is A hydrogen atom or an alkyl group having 1 or 2 carbon atoms); or R ² and R ⁴
Are bonded together to form a single bond; an epoxyethane derivative or a salt thereof. 48. R ¹ is an alkyl group having 1 or 2 carbon atoms; R ² is a hydrogen atom or a protecting group for a hydroxyl group; R ³ is an unsubstituted linear group having 10 to 14 carbon atoms. Linear or branched alkyl group, having a hydroxy as a substituent, having one or two double bonds, and having 5 to 7 carbon atoms, a linear or branched hydrocarbon group; It has formyl as a substituent and has one double bond.
Or a linear or branched hydrocarbon group having 2 and 4 to 6 carbon atoms, and having 2 carbon atoms as a substituent.
Or a straight-chain or branched hydrocarbon group having 3 or 4 double bonds and having 12 to 14 carbon atoms, having 3 or 4 double bonds, and having 3 or 4 carbon atoms. A linear or branched alkoxy group, a hydroxy group, or a compound of the formula -N ( ^R5b )
A group having (R ^6b ) (provided that R ^5b has 1 or 2 carbon atoms)
An alkyl group having 1 or 2 or an alkoxy group having 1 or 2 carbon atoms. R ^6b represents an alkyl group having 1 or 2 carbon atoms. And R ⁴ has 3 carbon atoms.
Or a linear or branched alkoxy group having four or a group having the formula —NH (R ^7b ) (provided that R ^7b
Represents a hydrogen atom. Or R ² and R ⁴ are bonded together to form a single bond; an epoxyethane derivative or a salt thereof.