Optical resolution methods for bicyclic compounds using enzymes

Patent metadata

Field	Value
Publication number	US-9394235-B2
Application number	US-201414511386-A
Country	US
Kind code	B2
Filing date	Oct 10, 2014
Priority date	Apr 10, 2012
Publication date	Jul 19, 2016
Grant date	Jul 19, 2016

Abstract

An object of the present invention is to efficiently produce an optically active bicyclic compound. The optically active bicyclic compound is efficiently produced using an enzyme.

First claim

The invention claimed is:

1. A method of producing a compound of formula (I):

comprising:
(1) allowing a racemic mixture of the compound of formula (I) and a compound of formula (II)

 to react in the presence of:
a reductase or an alcohol dehydrogenase,
a coenzyme, and
a compound selected from formic acid, a salt of formic acid, glucose and a combination of the foregoing,

in a buffer solution to convert the compound of formula (II) to a compound of formula (II′):

wherein R 1 is an ethyl group,
and
(2) separating the compound of formula (I) from the compound of formula (II′) to produce the compound of formula (I).

2. The method of claim 1 , wherein the reductase or the alcohol dehydrogenase is a formate dehydrogenase, and the coenzyme is NAD + or NADH.

3. The method of claim 1 , wherein the step (2) comprises reacting the compound of formula (II′) with a cyclic acid anhydride in the presence of a base, followed by the separation.

4. The method of claim 3 , wherein in the step (2), the cyclic acid anhydride is succinic anhydride, maleic anhydride, or phthalic anhydride, and the base is a tertiary amine.

5. The method of claim 1 , wherein the reaction in the step (1) is performed at a temperature of 20 to 40° C.

6. The method of claim 1 , wherein in the step (1), the reductase or the alcohol dehydrogenase is in an amount of 4 to 20% by weight with respect to the compound of formula (I) or the compound of formula (II), and the coenzyme is in an amount of 0.0001 to 0.001 equivalents with respect to the compound of formula (I) or the compound of formula (II).

7. The method of claim 1 , wherein the formic acid or the salt thereof is sodium formate.

8. The method of claim 1 , wherein the buffer solution is a phosphate buffer solution, and the phosphate buffer solution has a concentration of 50 to 200 mmol.

Assignees

• Daiichi Sankyo Co Ltd

Inventors

• Nakamura Yoshitaka
• Furuya Yukito
• Shimada Kousei
• Onishi Yoshiyuki

Classifications

• C12P7/02

  containing a hydroxy group · CPC title

• C07C45/85

  by treatment giving rise to a chemical modification (by chemisorption C07C45/79) · CPC title

• C07C205/50

  having nitro groups and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton · CPC title

• C12P41/002

  by oxidation/reduction reactions · CPC title

• C07C227/12 Primary

  Formation of amino and carboxyl groups · CPC title