丙氧杀鼠素A和B，新型脑啡肽酶B抑制剂。III. 丙氧杀鼠素A的全合成。

Propioxatins A and B, new enkephalinase B inhibitors. III. Total synthesis of propioxatin A.

作者信息

Inaoka Y, Takahashi S, Sato S

出版信息

J Antibiot (Tokyo). 1986 Oct;39(10):1382-5. doi: 10.7164/antibiotics.39.1382.

DOI:10.7164/antibiotics.39.1382

PMID:3781908

Abstract

Propioxatin A, a potent enkephalinase B inhibitor produced by Kitasatosporia setae SANK 60684, was synthesized. The synthetic route involved a regio-selective synthesis of O-benzyl-alpha-propylsuccinic acid monohydroxamic acid via the acid chloride of alpha-propylsuccinic acid. The stereoisomer of the N-acyl moiety of natural propioxatin A was analyzed by X-ray crystallography in the form of the di-O-benzyl ester and was determined as S. Devalyl propioxatin A synthesized by the same method showed a higher Ki value for enkephalinase B than propioxatin A.

摘要

合成了由北里孢菌SANK 60684产生的强效脑啡肽酶B抑制剂丙氧西汀A。合成路线包括通过α-丙基琥珀酸的酰氯区域选择性合成O-苄基-α-丙基琥珀酸单异羟肟酸。天然丙氧西汀A的N-酰基部分的立体异构体以二-O-苄基酯的形式通过X射线晶体学进行分析，并确定为S型。用相同方法合成的去缬氨酰丙氧西汀A对脑啡肽酶B的Ki值比丙氧西汀A更高。