Synthesis of 7-substituted farnesyl diphosphate analogues.
[structure: see text] Six farnesyl diphosphate analogues modified in the central isoprene unit have been prepared via our stereoselective vinyl triflate-mediated route to isoprenoids. The 7-allyl compound 6 is a modest inhibitor of mammalian protein-farnesyl transferase, but surprisingly the other five analogues are effective alternative substrates for this enzyme.
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Diwan S
DS
Rawat
Richard A
RA
Gibbs
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D011106:Polyisoprenyl Phosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012717:Sesquiterpenes; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; C004808:farnesyl pyrophosphate; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase