Stereospecific Synthesis of Peptidyl. alpha.-Keto Amides as Inhibitors of Calpain

SL Harbeson, SM Abelleira, A Akiyama…

Index: Harbeson, Scott L.; Abelleira, Susan M.; Akiyama, Alan; Barrett, Robert; Carroll, Renee M.; et al. Journal of Medicinal Chemistry, 1994 , vol. 37, # 18 p. 2918 - 2929

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Citation Number: 143

Abstract

Peptidyl a-keto amides have been synthesized and tested as inhibitors of the cysteine protease calpain. A stereospecific synthesis was devised in which Cbz-dipeptidyl-a-hydroxy amides were oxidized with TEMPOhypochlorite to the corresponding a-keto amides. This oxidation was accomplished in good yields and without epimerization of the chiral center adjacent to the ketone. The potent inhibition of porcine calpain I by the L, L diastereomers, ...