Patent ID: 6589777
Filing Date: 2003-07-08
Classification: C12P

Abstract:
A process for the stereoselective microbial reduction of racemic 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone, where said racemic 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone is a mixture of (4S)-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone and (4R)-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone having the formulae (4S)-(3,4dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone, and (4R)-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone, to a mixture of cis and trans tetralols having the formulae: to obtain unreacted (4S)-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone in an ee of greater than 50%, and unreacted (4R)-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone in an ee of less than 50%, which comprises:contacting racemic 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone with a microorganism, or an enzyme reduction system capable of accomplishing said reduction comprising an enzyme obtained from said microorganism and a co-factor for said enzyme; incubating the resulting mixture under conditions sufficient to yield said (trans) (1S,4R) tetralol, said (cis) (1R,4R) tetralol, said (trans) (1R,4S) tetralol, and said (cis) (1S,4S) tetralol, and to leave substantially unreacted (4S)-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone, resulting in unreacted (4S)-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone being present in ee greater than 50%, and unreacted (4R)-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone being present in ee less than 50%; wherein said microorganism is selected from the group consisting of Hansenula polymorpha ATCC No. 26012, Hansenula polymorpha ATCC No. 74449, Absidia coerulea ATCC No. 20137, Geotrichum candidum ATCC No. 34614, Geotrichum candidum ATCC No. 62401, Mortierella isabellina ATCC No. 42613, Mortierella isabellina ATCC No. 38063, Mortierella vinacea ATCC No. 09515, Penicillium notatum ATCC No. 36740, Blastoschizomyces capitalus ATCC No. 28575, Monosporium olivaceum v. major ATCC No. 36300, Aureobasidium pullulans ATCC No. 16623, Debaryomyces polymorphus ATCC No. 20280, Saccharomyces cerevisiae ATCC No. 15248, Candida schatavii ATCC No. 24409, Pichi fabianii ATCC No. 16755 and Streptomyces rimosus ss. rimosus ATCC No. 10970; and such mutants thereof capable of accomplishing said reduction; and recovering said unreacted (4S)-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone from said resulting mixture.