Patent ID: 7645599

Claim:
A method for producing (R)-3-quinuclidinol hydrochloride having an optical purity of 93.4% ee or higher, the method comprising the steps of: (a) contacting a 3-quinuclidinone at a concentration of 5 to 50% with an isolated protein selected from the group consisting of the following (i) to (iii) in the presence of a reduced coenzyme to perform asymmetric reduction, a coenzyme-regenerating enzyme which regenerates said reduced coenzyme from its oxidized form, and a substrate for said coenzyme-regenerating enzyme; (i) an isolated protein comprising the amino acid sequence of SEQ ID NO:2; (ii) an isolated protein comprising the amino acid sequence of SEQ ID NO:2, wherein one to five amino acids have been substituted, deleted, inserted, and/or added, and having the activity of producing (R)-3-quinuclidinol from 3-quinuclidinone by asymmetric reduction; and (iii) an isolated protein comprising an amino acid sequence having 95% or higher identity to the amino acid sequence of SEQ ID NO:2, and having the activity of producing (R)-3-quinuclidinol from 3-quinuclidinone by asymmetric reduction; (b) recovering the (R)-3-quinuclidinol; (c) adjusting the pH of the (R)-3-quinuclidinol solution to alkaline levels to yield free (R)-3-quinuclidinol; (d) extracting the free (R)-3-quinuclidinol with n-butanol; (e) adding hydrochloric acid to the extract; (f) removing moisture from the extract; and (g) crystallizing (R)-3-quinuclidinol hydrochloride in the solution obtained in (f).