The preparation of zaragozic acid A analogues by directed biosynthesis.
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.
Chen
T S
TS
Merck Research Laboratories, Rahway, New Jersey 07065.
Petuch
B
B
MacConnell
J
J
White
R
R
Dezeny
G
G
Arison
B
B
Bergstrom
J D
JD
Colwell
L
L
Huang
L
L
Monaghan
R L
RL
D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors*; D005658:Fungi / Q000187:drug effects / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D014233:Tricarboxylic Acids / Q000378:metabolism*
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D014233:Tricarboxylic Acids; C075117:squalestatin 1; D013186:Farnesyl-Diphosphate Farnesyltransferase