Resolution of racemic indene oxide to yield (1S,2R)-indene oxide using Diplodia gossipina
AssigneeMerck & Co., Inc.
InventorsMichel M. Chartrain, Chris H. Senanayake, John P. N. Rosazza, Jinyou Zhang
Life of this patent
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Abstract
A process is disclosed that hydrolyzes, by the action of an epoxide hydrolase of Diplodia gossipina (alternatively named Diplodia gossypina) ATCC 16391 or ATCC 10936, the undesired enantiomer of racemic indene oxide, an epoxide of indan.
Claims5
A process of separating (1S,2R) indanyl epoxide in substantially 100% enantiomeric excess from a mixture comprising (1R,2S) indanyl epoxide and (1S,2R) indanyl epoxide, comprising the steps of
- (a) providing a mixture comprising (1R,2S) indanyl epoxide and (1S,2R) indanyl epoxide in buffer;
- (b) incubating the mixture with a suspension of fungal cells selected from the group consisting of Diplodia gossipina and Lasiodiplodia theobromae until substantially all of the (1R, 2S) indanyl epoxide is consumed;
- and
- (c) isolating the resulting (1S,2R) indanyl epoxide.
A process of purifying (1S,2R) indanyl epoxide in substantially 100% enantiomeric excess from a mixture comprising (1R,2S) indanyl epoxide and (1S,2R) indanyl epoxide, comprising the steps of
- (a) providing a mixture comprising (1R,2S) indanyl epoxide and (1S,2R) indanyl epoxide, at a concentration of about 1 g/L of said mixture in about 0.1M Tris, pH about 7.5, containing about 10% acetonitrile;
- (b) incubating the mixture with a suspension of fungal cells derived from Diplodia gossipina ATCC 16391, until substantially all of the (1R, 2S) indanyl epoxide is consumed;
- and
- (c) isolating the resulting (1S,2R) indanyl epoxide.
A process of purifying (1S,2R) indanyl epoxide in substantially 100% enantiomeric excess from a mixture comprising (1R,2S) indanyl epoxide and (1S,2R) indanyl epoxide, comprising the steps of
- (a) providing a mixture comprising (1R,2S) indanyl epoxide and (1S,2R) indanyl epoxide, at a concentration of about 1 g/L of said mixture in about 0.1M Tris, pH about 7.5, containing about 10% acetonitrile;
- (b) incubating the mixture with a suspension of fungal cells derived from Diplodia gossipina ATCC 10936, until substantially all of the (1R, 2S) indanyl epoxide is consumed;
- and
- (c) isolating the resulting (1S,2R) indanyl epoxide.
Dependencies are inferred from the claim text.