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.
Rawat
Diwan S
DS
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Gibbs
Richard A
RA
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