Synthesis of gerfelin and related analogous compounds.

Gerfelin, an inhibitor of human geranylgeranyl diphosphate (GGPP) synthase that has been isolated from a culture broth of Beauveria felina QN22047, was synthesized in 4 and 3 steps starting from 2,4-dihydroxy-6-methylbenzoic acid and 3,4,5-trihydroxytoluene, respectively. An effective ligand, 2-(di-tert-butylphosphino)biphenyl, was used in the palladium-catalyzed diaryl ether-forming reaction. Five analogous compounds of gerfelin were also synthesized for a study of the structure-activity relationship.