Herranz R, Castro-Pichel J, García-López M T, Gómez-Monterrey I, Pérez C, Vinuesa S
Instituto de Química Médica, Juan de la Cierva, Madrid, Spain.
Arch Pharm (Weinheim). 1993 Jul;326(7):395-8. doi: 10.1002/ardp.19933260705.
The synthesis of (6R,5S,2RS)-6-amino-5-hydroxy-2-isobutyl-4-oxo-7- phenylheptanoic acid (9), a carbaanalogue of the aminopeptidase (AP) inhibitor bestatin (1) is described. This synthesis was carried out by a malonic ester alkylation with the suitably protected halomethyl ketone of (2S,3R)-AHPBA*), followed by a second alkylation with isobutyl bromide of the resulting 4-ketodiester, and subsequent decarboxylation and deprotection. The inhibitory potencies of the 1:1 diastereomeric mixture 9 against AP-B, AP-M and Leu-AP were approximately 10-fold lower than those of bestatin.
描述了（6R，5S，2RS）-6-氨基-5-羟基-2-异丁基-4-氧代-7-苯基庚酸（9）的合成，它是氨肽酶（AP）抑制剂贝他汀（1）的碳类似物。该合成通过丙二酸酯与（2S，3R）-AHPBA*的适当保护的卤甲基酮进行烷基化反应，然后用异丁基溴对所得的4-酮二酯进行第二次烷基化，随后进行脱羧和脱保护。1:1非对映异构体混合物9对AP-B、AP-M和亮氨酸氨肽酶的抑制效力比贝他汀低约10倍。
