Large scale preparation of chiral building blocks for the P3 site of renin inhibitors.

Abstract:

:Racemic ethyl 2-benzyl-3-(tert-butylsulfonyl)propionate (1) and racemic ethyl 2-benzyl-3-[[1-methyl-1-((morpholin-4-yl)carbonyl)ethyl]sulfonyl] propionate (3) were enantioselectively hydrolyzed by subtilisin Carlsberg generating the respective (S)-acids used as building blocks for renin inhibitors. The esters were readily converted as emulsions at elevated temperature, in a suspended form or a two-phase-liquid system. The enzyme maintained its excellent selectivity and a good activity also at high initial substrate concentrations (up to 50% w/w). The enzymatic reaction and work-up were optimized and scaled up. Emulsion problems during work-up encountered with these highly concentrated mixtures were solved by application of a disk separator for phase separation.

journal_name

Bioorg Med Chem

authors

Doswald S,Estermann H,Kupfer E,Stadler H,Walther W,Weisbrod T,Wirz B,Wostl W

doi

10.1016/0968-0896(94)80007-3

subject

Has Abstract

pub_date

1994-06-01 00:00:00

pages

403-10

issue

6

eissn

0968-0896

issn

1464-3391

pii

0968-0896(94)80007-3

journal_volume

2

pub_type

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