埃默胺及其类似物的长链脂肪酸氧化的化学性质和抑制活性。

Chemistry and inhibitory activity of long chain fatty acid oxidation of emeriamine and its analogues.

作者信息

Shinagawa S, Kanamaru T, Harada S, Asai M, Okazaki H

出版信息

J Med Chem. 1987 Aug;30(8):1458-63. doi: 10.1021/jm00391a030.

Abstract

Emericedins A, B, and C, new betaines having inhibitory activity of long chain fatty acid oxidation, were isolated from the culture broth of Emericella quadrilineata IFO 5859. Their structures were determined by spectroscopic analyses as (R)-3-(acylamino)-4-(trimethylammonio)butyrate (acyl: A, acetyl; B, propionyl; C, n-butyryl). Structural confirmation and assignment of absolute configuration were made by chemical synthesis from L-asparagine. Deacylation of emericedin gave a potent derivative, (R)-3-amino-4-(trimethylammonio)butyrate, designated as emeriamine. In order to study the structure-activity relations, various analogues of emeriamine, including a stereoisomer, were prepared. Among them, N-palmitoyl and N-myristoyl derivatives showed much stronger inhibition of fatty acid oxidation than emeriamine.

摘要

从四线埃默里氏菌IFO 5859的培养液中分离出了具有长链脂肪酸氧化抑制活性的新型甜菜碱——埃默里辛A、B和C。通过光谱分析确定它们的结构为（R）-3-（酰基氨基）-4-（三甲基铵）丁酸酯（酰基：A，乙酰基；B，丙酰基；C，正丁酰基）。通过L-天冬酰胺的化学合成对结构进行了确认并确定了绝对构型。埃默里辛脱酰基得到一种有效的衍生物，即（R）-3-氨基-4-（三甲基铵）丁酸酯，命名为埃默里胺。为了研究构效关系，制备了包括立体异构体在内的各种埃默里胺类似物。其中，N-棕榈酰基和N-肉豆蔻酰基衍生物对脂肪酸氧化的抑制作用比埃默里胺强得多。