alpha-Keto amide inhibitors of aminopeptidases.
alpha-Keto amide inhibitors of aminopeptidases.
复制标题
氨肽酶的α-酮酰胺抑制剂。
DOI：
10.1021/jm00081a005
复制
发表时间：
1992
影响因子：
7.3
通讯作者：
Rich,DH
中科院分区：
文献类型：
--
作者：
Ocain,TD;Rich,DH
Results Chemistry. The synthesis of the requisite Boc-protected-hydroxy amide starting materials has beenpre-viously described. 6, 7 The Bocketones 5-7 (TableI) were synthesized in moderate yields (35-55%) byusing pyridinium dichromate (PDC) in acetic acid. Low yields of ketone were generally caused by incomplete oxidation, and thus starting material could be recycled. It should be noted that oxidations employing activated DMSO (eg S03-py, DMSO, NEtg) gave very poor yields of desired product (< 25%). The methyl ketone (10) derived from Bocleucine, was obtained by addition of methyllithium to the free acid of Boc-leucine. The Boc group was removed from the-keto amides by using 4 N HCl-dioxane, and the HC1 salts 2-4 were isolated by filtration after trituration with ether (Scheme I).Inhibition constants for each analogue were determined as previously described. 7 Initially we attempted to de-termine the importance of chirality at the side-chain bearing carbon (C-3) on inhibitor potency by oxidizing the SR and SS alcohol precursors separately. However, epim-erization adjacent to the ketone occurred rapidly so that the resulting ketones were obtained as variable mixtures
