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Enzymatic Hydrolysis of a Prochiral 3‐Substituted Glutarate Ester, an Intermediate in the Synthesis of an NK 1 /NK 2 Dual Antagonist
Author(s) -
Homann Michael J.,
Vail Robert,
Morgan Brian,
Sabesan Vijay,
Levy Cliff,
Dodds David R.,
Zaks Aleksey
Publication year - 2001
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/1615-4169(200108)343:6/7<744::aid-adsc744>3.0.co;2-e
Subject(s) - chemistry , desymmetrization , candida antarctica , yield (engineering) , hydrolysis , enzyme , lipase , substrate (aquarium) , enzymatic hydrolysis , biocatalysis , transesterification , stereochemistry , organic chemistry , catalysis , enantioselective synthesis , reaction mechanism , materials science , oceanography , geology , metallurgy
An enzymatic process for desymmetrization of the prochiral diethyl 3‐[3',4'‐dichlorophenyl]glutarate, 1 , an intermediate in the synthesis of a series of neurokinin (NK) receptor antagonists, has been developed and scaled up. The transformation catalyzed by Candida antarctica lipase B in either the free or the immobilized form was carried out at 100 g/L of substrate and proceeded with an average conversion of 97%. In the pilot plant, the process produced 200 kg of 2 in 3 batches with ee >99% and an average isolated yield of 80%. The immobilized enzyme preparation was particularly effective, achieving over 70,000 enzyme turnovers per batch.