通过定向生物合成制备扎戈齐酸A类似物。

The preparation of zaragozic acid A analogues by directed biosynthesis.

作者信息

Chen T S, Petuch B, MacConnell J, White R, Dezeny G, Arison B, Bergstrom J D, Colwell L, Huang L, Monaghan R L

机构信息

Merck Research Laboratories, Rahway, New Jersey 07065.

出版信息

J Antibiot (Tokyo). 1994 Nov;47(11):1290-4. doi: 10.7164/antibiotics.47.1290.

DOI:10.7164/antibiotics.47.1290

PMID:8002393

Abstract

Zaragozic acid A analogues are produced by an unidentified sterile fungus when it is exogenously supplied with 2-thiophenecarboxylic acid, 3-thiophenecarboxylic acid, 2-furoic acid, 2-fluorobenzoic acid, 3-fluorobenzoic acid, or 4-fluorobenzoic acid. The analogues carry 2-thiophenyl, 3-thiophenyl, 2-furyl, o-fluorophenyl, m-fluorophenyl, or p-fluorophenyl group, respectively, at C-6' of the C-1 alkyl side chain replacing the phenyl group of natural zaragozic acid A. All the new analogues of zaragozic acid A possess picomolar inhibitory activity against squalene synthase in vitro.

摘要

当一种未鉴定的无菌真菌被外源供应2-噻吩羧酸、3-噻吩羧酸、2-呋喃甲酸、2-氟苯甲酸、3-氟苯甲酸或4-氟苯甲酸时，会产生扎拉戈昔酸A类似物。这些类似物在C-1烷基侧链的C-6'位分别带有2-噻吩基、3-噻吩基、2-呋喃基、邻氟苯基、间氟苯基或对氟苯基，取代了天然扎拉戈昔酸A的苯基。扎拉戈昔酸A的所有新类似物在体外对鲨烯合酶都具有皮摩尔级的抑制活性。