浅蓝菌素及其类似物的合成。II. 浅蓝菌素的碳环类似物dl-碳青霉烯浅蓝菌素的合成及生物活性

Syntheses of cerulenin and its analogs. II. Synthesis and biological activity of dl-carbacerulenin, a carbocyclic analog of cerulenin.

作者信息

Shimazawa R, Ogawa Y, Morisaki N, Funabashi H, Kawaguchi A, Iwasaki S

机构信息

Institute of Applied Microbiology, University of Tokyo, Japan.

出版信息

Chem Pharm Bull (Tokyo). 1992 Nov;40(11):2954-7. doi: 10.1248/cpb.40.2954.

DOI:10.1248/cpb.40.2954

PMID:1477910

Abstract

2,3-Epoxy-4-hydroxy-4-((E,E)-3,6-octadienyl)cyclopentanone (dl-carbacerulenin 5) was synthesized via the epoxyketones 15a and 15b as a mimic of the active form of the antibiotics cerulenin 1, a potent inhibitor of fatty acid synthetase (FAS). The monobenzyl ethers (12 and 13), synthetic intermediates of 15, were prepared by direct benzylation of the epoxycyclopentene (7). Inhibitory activity of synthesized 5 toward yeast FAS was less than that of cerulenin by a factor of 1000.

摘要

2,3-环氧-4-羟基-4-((E,E)-3,6-辛二烯基)环戊酮（dl-碳青霉素烯醇5）通过环氧酮15a和15b合成，作为抗生素碳青霉素烯1（一种脂肪酸合成酶（FAS）的有效抑制剂）活性形式的模拟物。15的合成中间体单苄基醚（12和13）通过环氧环戊烯（7）的直接苄基化制备。合成的5对酵母FAS的抑制活性比碳青霉素烯低1000倍。