Stereoselective microbial reduction of N-(4-(1-oxo-2-chloroacetyl ethyl) phenyl methane sulfonamide

• Published in: Applied microbiology and biotechnology 1993-11, Vol.40 (2-3), p.241-245
• Main Authors: Patel, RameshN, Banerjee, Amit, McNamee, ClydeG, Szarka, LaszloJ
• Format: Article
• Language: English
• Subjects: Hansenula polymorpha; Nocardia; Rhodococcus
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/BF00170373

Several microbial cultures were screened for the ability to catalyse the reduction of N-(4-(1-oxo-2-chloroacetyl ethyl) phenyl methane sulfonamide (1). The chiral intermediate (+)N-(4-(1-hydroxy-2-chloroethyl) phenyl methane sulfonamide (2) was prepared by the stereoselective microbial reduction of the parent ketone 1. Compound 2 is a potential chiral intermediate for synthesis of 4-(2-isopropylamino-1-hydroxyethyl) phenyl methanesulfonanilide (D-sotalol), a beta-receptor antagonist. Microorganisms from the genera Rhodococcus, Nocardia, and Hansenula reduced 1 to 2. A reaction yield of >50% and optical purities of >90% were obtained. The best strain (H. polymorpha ATCC 26012) effectively reduced compound 1 to compound 2 in 95% reaction yield and 99% optical purity. Compound 2 (8.2 g) was isolated from a 3-1 preparative batch in 68% overall yield. Isolated compound 2 had a specific rotation of +20 degree (CH sub(2)Cl sub(2), C-1), an optical purity of 99.5%, and a chemical purity of 97% as analyzed by gas chromatography and HPLC. The nuclear magnetic resonance and mass spectra of compound 2 prepared by bioreduction and a standard chemical sample of 2 were virtually identical. Cell extracts of H. polymorpha in the presence of glucose dehydrogenase, glucose and nicotinamide adenine dinucleotide (NAD super(+)) catalyzed the reduction of 1 to 2 with 98% reaction yield and resulted in an optical purity of 99.4%. (DBO)