Methods for producing optically active alcohols
OwnerHiroaki Yamamoto, Momoko Ueda +2inventors
InventorsHiroaki Yamamoto, Momoko Ueda, Ritsuzui Pan, Takeshi Hamatani
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Abstract
A method for producing optically active alcohols is provided. Optically active alcohols are useful intermediates in pharmaceutical production. The method of the present invention enables simple and efficient production of optically active alcohols with a high optical purity. According to the production method disclosed, optically active alcohols are produced via asymmetric reduction of 3-quinuclidinone using tropinone reductase-I. For example, the use of tropinone reductase-I derived from plants like Datura stramonium and Hyoscyamus niger allows the production of high optical purity (R)-3-quinuclidinol as shown in Formula (1) below. Formula (1): 1
Claims31
A method for producing an optically active alcohol, the method comprising the steps of contacting a ketone with an enzymatic material having tropinone reductase-I activity in the presence of a reduced coenzyme to perform asymmetric reduction and recovering an optically active alcohol.
A method for producing (R)-3-quinuclidinol hydrochloride, the method comprising the steps of:
- (a) making the pH of (R)-3-quinuclidinol solution alkaline to form free (R)-3-quinuclidinol;
- (b) extracting free (R)-3-quinuclidinol with n-butanol;
- (c) adding hydrochloric acid to the extract;
- (d) removing moisture from the extract;
- and
- (e) crystallizing (R)-3-quinuclidinol hydrochloride in the solution obtained in (d).
A method for producing (R)-3-quinuclidinol, the method comprising the steps of:
- (a) dissolving (R)-3-quinuclidinol hydrochloride in a first solvent, wherein the first solvent is capable of dissolving (R)-3-quinuclidinol hydrochloride at a concentration of 1% or higher;
- (b) making the pH of the solution obtained in (a) alkaline to form free (R)-3-quinuclidinol;
- (c) adding a second solvent to the (R)-3-quinuclidinol solution, wherein the second solvent can be substituted for the first solvent by distilling off the first solvent from a mixture of the first and second solvents, dissolves free (R)-3-quinuclidinol with lower solubility than the first solvent, and allows to crystallize free (R)-3-quinuclidinol from itself;
- (d) distilling off the first solvent;
- and
- (e) crystallizing (R)-3-quinuclidinol in the solution obtained in (d).
A method for producing (R)-3-quinuclidinol, the method comprising the steps of:
- (a) making the pH of (R)-3-quinuclidinol solution alkaline to form free (R)-3-quinuclidinol;
- (b) extracting free (R)-3-quinuclidinol with n-butanol;
- and
- (c) adding an organic solvent to the extract, wherein the organic solvent can be substituted for n-butanol by distilling off n-butanol from a mixture of n-butanol and the organic solvent, dissolves free (R)-3-quinuclidinol with lower solubility than n-butanol, and allows to crystallize free (R)-3-quinuclidinol from itself;
- (d) distilling off n-butanol;
- and
- (e) crystallizing (R)-3-quinuclidinol in the solution obtained in (d).
A vector comprising and capable of expressing a DNA encoding tropinone reductase-I and a DNA encoding an enzyme of regenerating a reduced coenzyme from the oxidized form.
A transformant carrying and capable of expressing (1) a DNA encoding tropinone reductase-I or a vector comprising a DNA encoding tropinone reductase-I and (2) a DNA encoding an enzyme of regenerating a reduced coenzyme from the oxidized form or a vector comprising a DNA encoding an enzyme of regenerating a reduced coenzyme from the oxidized form.
Dependencies are inferred from the claim text.