Porcine liver esterase-catalyzed enantioselective hydrolysis of a prochiral diester into its optically pure (S)-ester acid, a precursor to a growth hormone secretagogue.
A limited screen of several commercially-available and internally-produced lipases and esterases identified porcine liver esterase as a suitable biocatalyst for the enantioselective hydrolysis of a diester into its (S)-ester acid with high optical purity (99%). This (S)-ester acid is a precursor to an experimental growth hormone secretagogue. After identifying xanthan gum as the best emulsifier and optimizing the reaction conditions, hydrolysis rates of 1 g/l.h and final (S)-ester acid (ee > 99%) titers of about 8.5 g/l were routinely achieved. This process supported the production of preparative amounts of optically pure (S)-ester (ee > 99%) with a high reaction yield of 82%. Upon purification, the (S)-ester was successfully used in the subsequent synthetic steps to yield the growth hormone secretagogue.
Chartrain
M
M
Department of Bioprocess R&D, Merck Research Laboratories, P.O. Box 2000 RY80Y-105, Rahway, New Jersey 07065, USA.
Maligres
P
P
Cohen
D
D
Upadhyay
V
V
Pecore
V
V
Askin
D
D
Greasham
R
R