The squalestatins, novel inhibitors of squalene synthase produced by a species of Phoma. II. Structure elucidation.
Three novel fungal metabolites 1-3 isolated from cultures of a Phoma sp. C2932, are potent and selective inhibitors of squalene synthase. Their structures have been determined by a combination of spectroscopic, X-ray crystallographic and chemical methods; these natural products incorporate the highly functionalised bicyclic core, [1S-(1 alpha, 3 alpha, 4 beta, 5 alpha, 6 alpha, 7 beta]-4,6,7-trihydroxy- 2,8-dioxabicyclo-[3.2.1]octane-3,4,5-tricarboxylic acid.
Sidebottom
P J
PJ
Structural Chemistry Department, Glaxo Group Research Limited, Greenford, Middlesex, United Kingdom.
Highcock
R M
RM
Lane
S J
SJ
Procopiou
P A
PA
Watson
N S
NS
D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014233:Tricarboxylic Acids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D000935:Antifungal Agents; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D014233:Tricarboxylic Acids; C075117:squalestatin 1; D013186:Farnesyl-Diphosphate Farnesyltransferase