Method for producing thiolane skeleton-type glycoconjugate, and thiolane skeleton-type glycoconjugate

Patent metadata

Field	Value
Publication number	US-9884882-B2
Application number	US-201615238232-A
Country	US
Kind code	B2
Filing date	Aug 16, 2016
Priority date	Feb 18, 2014
Publication date	Feb 6, 2018
Grant date	Feb 6, 2018

Abstract

There is provided a production method of a compound represented by the following formula (II) through a step of reacting a compound represented by the following General Formula (I) with a sulfur compound.

In General Formulas (I) and (II), R 1 represents a hydrogen atom or an acyl group, R 2 represents a hydrogen atom, a fluorine atom, an acyloxy group, an arylmethyloxy group, an allyloxy group, an arylmethyloxycarbonyloxy group, or an allyloxycarbonyloxy group, R 3 represents a hydrogen atom or an acyloxy group, R 5 represents an alkyl group or an aryl group, and X represents a leaving group. Here, in a case where R 2 is a fluorine atom, an acyloxy group, an arylmethyloxy group, an allyloxy group, an arylmethyloxycarbonyloxy group, or an allyloxycarbonyloxy group, R 3 is an acyloxy group.

First claim

What is claimed is:

1. A production method of a compound represented by the following General Formula (II) through a step of reacting a compound represented by the following General Formula (I) with a sulfur compound, via the compound represented by General Formula (III),

A represents SH or S − ,
wherein, in General Formulas (I) (II), and (III), R 2 represents a hydrogen atom, a fluorine atom, an acyloxy group having 1 to 20 carbon atoms, which may have a substituent selected from a halogen atom, an alkyl group, an aryl group, a heterocyclic group, an alkoxy group, an aryloxy group, an alkylthio group, and an arylthio group, an arylmethyloxy group having 7 to 20 carbon atoms, which may have a substituent selected from a halogen atom, an alkyl group, an aryl group, a heterocyclic group, an alkoxy group, an aryloxy group, an alkylthio group, and an arylthio group, an allyloxy group, which may have a substituent selected from a halogen atom, an alkyl group, an aryl group, a heterocyclic group, an alkoxy group, an aryloxy group, an alkylthio group, and an arylthio group, an arylmethyloxycarbonyloxy group having 8 to 21 carbon atoms, which may have a substituent selected from a halogen atom, an alkyl group, an aryl group, a heterocyclic group, an alkoxy group, an aryloxy group, an alkylthio group, and an arylthio group, or an allyloxycarbonyloxy group, which may have a substituent selected from a halogen atom, an alkyl group, an aryl group, a heterocyclic group, an alkoxy group, an aryloxy group, an alkylthio group, and an arylthio group, R 3 represents a hydrogen atom or an acyloxy group having 1 to 20 carbon atoms, which may have a substituent selected from a halogen atom, an alkyl group, an aryl group, a heterocyclic group, an alkoxy group, an aryloxy group, an alkylthio group, and an arylthio group, R 5 represents an aryl group having 6 to 19 carbon atoms, which may have a substituent selected from a halogen atom, an alkyl group, an aryl group, a heterocyclic group, an alkoxy group, an aryloxy group, an alkylthio group, and an arylthio group, and X represents a halogen atom, an alkylsulfonyloxy group having 1 to 10 carbon atoms, or an arylsulfonyloxy group having 6 to 16 carbon atoms;
wherein, if R 2 is the fluorine atom, the acyloxy group, the arylmethyloxy group, the allyloxy group, the arylmethyloxycarbonyloxy group, or the allyloxycarbonyloxy group, R 3 is the acyloxy group; and
wherein the sulfur compound is hydrogen sulfide or a salt thereof.

2. The production method according to claim 1 ,
wherein the compound represented by General Formula (II) is any one of the following General Formulas (II-1) to (II-14),

wherein, in General Formulas (II-1) to (II-14), R 1 is a hydrogen atom and R 5 has the same meaning R 5 in General Formula (II), each of R 2a and R 3a independently represents an alkyl group having 1 to 20 carbon atoms, which may have a substituent selected from a halogen atom, an alkyl group, an aryl group, a heterocyclic group, an alkoxy group, an aryloxy group, an alkylthio group, and an arylthio group or an aryl group having 6 to 19 carbon atoms, which may have a substituent selected from a halogen atom, an alkyl group, an aryl group, a heterocyclic group, an alkoxy group, an aryloxy group, an alkylthio group, and an arylthio group, R 2b represents —CH 2 —Ar, an allyl group, —C(═O)OCH 2 —Ar, or an allyloxycarbonyl group wherein Ar represents an aryl group having 6 to 19 carbon atoms, which may have a substituent selected from a halogen atom, an alkyl group, an aryl group, a heterocyclic group, an alkoxy group, an aryloxy group, an alkylthio group, and an arylthio group, and, the direct bond represented by a dashed line having a constant thickness which is bonded to a thiolane ring is positioned at any one of an α-position or a β-position.

3. The production method according to claim 1 ,
wherein R 5 is an aryl group, and R 3 is an arylcarbonyloxy group.

4. The production method according to claim 1 ,
wherein R 5 is a phenyl group, a 4-methylphenyl group, a 4-phenylphenyl group, or a 2-naphthyl group, and R 3 is a phenylcarbonyloxy group, a 4-methylphenylcarbonyloxy group, a 4-phenylphenylcarbonyloxy group, or a 2-naphthylcarbonyloxy group.

5. The production method according to claim 1 ,
wherein, after a compound represented by the following General Formula (IIA) is synthesized in the step of reacting the compound represented by General Formula (I) with a sulfur compound, a compound represented by the following General Formula (IIB) is synthesized in a step of acylating the compound represented by General Formula (IIA),

wherein, in General Formulas (IIA) and (IIB), R 2 , R 3 , and R 5 have the same meaning as R 2 , R 3 , and R 5 in General Formula (II), respectively, and R 1a represents an acyl group having 1 to 20 carbon atoms, which may have a substituent selected from a halogen atom, an alkyl group, an aryl group, a heterocyclic group, an alkoxy group, an aryloxy group, an alkylthio group, and an arylthio group.

6. The production method according to claim 1 ,
wherein R 1 is an acetyl group or an arylcarbonyl group.

7. The production method according to claim 1 ,
wherein the sulfur compound is MSH or M 2 S in which M is an alkali metal.

8. A compound represented by any one of the following General Formulas (II-4) to (II-7), (II-13) and (II-14),

wherein, in General Formulas (II-4) to (II-7), (II-13) and (II-14), R 1 represents a hydrogen atom or an acyl group having 1 to 20 carbon atoms, which may have a substituent selected from a halogen atom, an alkyl group, an aryl group, a heterocyclic group, an alkoxy group, an aryloxy group, an alkylthio group, and an arylthio group, and R 3a represents an aryl group having 6 to 19 carbon atoms, which may have a substituent selected from a halogen atom, an alkyl group, an aryl group, a heterocyclic group, an alkoxy group, an aryloxy group, an alkylthio group, and an arylthio group, and R 5 represents an aryl group having 6 to 19 carbon atoms, which may have a substituent selected from a halogen atom, an alkyl group, an aryl group, a heterocyclic group, an alkoxy group, an aryloxy group, an alkylthio group, and an arylthio group, R 2b represents —CH 2 —Ar, an allyl group, —C(═O)OCH 2 —Ar, or an allyloxycarbonyl group, wherein Ar represents an aryl group having 6 to 19 carbon atoms, which may have a substituent selected from a halogen atom, an alkyl group, an aryl group, a heterocyclic group, an alkoxy group, an aryloxy group, an alkylthio group, and an arylthio group, and the direct bond represented by a dashed line having a constant thickness which is bonded to a thiolane ring is positioned on any one of an α-side or a β-side.

9. The compound according to claim 8 ,
wherein R 1 is a hydrogen atom, an acetyl group, or an arylcarbonyl group, and each of R 3a and R 5 is independently an aryl group.

10. The compound according to claim 8 ,
wherein each of R 3a and R 5 is independently a phenyl group, a 4-methylphenyl group, a 4-phenylphenyl group, or a 2-naphthyl group.

11. A compound represented by any one of the following General Formula (II-6B)(II-13′), and (II-14′),

Assignees

• Fujifilm Corp

Inventors

• Ito Takayuki
• Watanabe Toru
• Okada Hideki
• Kuniyoshi Hidenobu

Classifications

• C07H15/04

  attached to an oxygen atom of the saccharide radical · CPC title

• C07D333/32

  Oxygen atoms · CPC title

• C07H15/18

  Acyclic radicals, substituted by carbocyclic rings · CPC title

• C07H13/08 Primary

  having the esterifying carboxyl radicals directly attached to carbocyclic rings · CPC title