An asymmetric synthesis of l-694,458, a human leukocyte elastase inhibitor, via novel enzyme resolution of β-lactam esters

RJ Cvetovich, M Chartrain, FW Hartner…

Index: Cvetovich, Raymond J.; Chartrain, Michel; Hartner Jr., Frederick W.; Roberge, Christopher; Amato, Joseph S.; Grabowski, Edward J. J. Journal of Organic Chemistry, 1996 , vol. 61, # 19 p. 6575 - 6580

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Citation Number: 68

Abstract

A convergent synthesis of [S-(R*, S*)]-2-[4-[(4-methylpiperazin-1-yl) carbonyl] phenoxy]-3, 3- diethyl-N-[1-[3, 4-(methylenedioxy) phenyl] butyl]-4-oxo-1-azetidinecarboxamide (L-694,458, 1), a potent human leukocyte elastase inhibitor, was achieved via chiral synthesis of key intermediates:(S)-3, 3-diethyl-4-[4'-[(N-methylpiperazin-1-yl) carbonylphenoxy]-2- azetidinone (2) and (R)-α-propylpiperonyl isocyanate (3). Synthesis of β-lactam 2 was ...

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