Chemoenzymatic synthesis of (R)-Nifenalol via yeast-mediated symmetric reduction of ketones

MEDI 325

Jian-He Xu, jianhexu@ecust.edu.cn and Wei Yang. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China
A broad range of prochiral ketones were efficiently reduced to the corresponding optically active secondary alcohols using resting cells of a newly isolated yeast Rhodotorula sp. AS2.2241. The microbial reduction system exhibited high activity and enantioselectivity (obeying Prelog's rule) in the reduction of various aromatic ketones and acetylpyridines (>97%ee), and moderate to high enantioselectivity in the reduction of alpha- and beta-keto esters. (R)-Nifenalol, a beta-adrenergic blocker, was successfully synthesized from an optically pure chirl synthon, 2-bromo-1(R)-(4-nitrophenyl)ethanol (97%ee), which was easily prepared through asymmetric reduction of 2-bromo-1-(4-nitrophenyl)ethanone employing Rhodotorula sp. AS2.2241. The simple preparation and the high activity of the biocatalyst turn this system into a versatile tool for organic synthesis.
 

General Poster Session
7:00 PM-9:00 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster

Division of Medicinal Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006