THE PREPARATION OF ZARAGOZIC ACID A ANALOGS BY DIRECTED BIOSYNTHESIS

Zaragozic acid A analogues are produced by an unidentified sterile fun gus when it is exogenously supplied with 2-thiophenecarboxylic acid, 3 -thiophenecarboxylic acid, 2-furoic acid, 2-fluorobenzoic acid, 3-fluo robenzoic acid, or 4-fluorobenzoic acid. The analogues carry 2-thiophe nyl, 3-thiophenyl, 2-furyl, o-fluorophenyl, m-fluorophenyl, or p-fluor ophenyl group, respectively, at C-6' of the C-1 alkyl side chain repla cing the phenyl group of natural zaragozic acid A. All the new analogu es of zaragozic acid A possess picomolar inhibitory activity against s qualene synthase in vitro.