Farnesyl and geranylgeranyl pyrophosphate analogs incorporating benzoylbenzyl ethers: Synthesis and inhibition of yeast protein farnesyltransferase

Article abstract of DOI:10.1016/S0040-4039(96)02066-7

The syntheses of two photoactive analogs (1a and 1b) of farnesyl pyrophosphate that incorporate stable ether-linked benzophenones are described. Compounds 1a and 1b were prepared from geraniol in 17% overall yield. Both in and 1b are competitive inhibitors of yeast protein farnesyltransferase with respect to farnesyl pyrophosphate and have K₁ values of 45 nM and 49 nM. Upon photolysis for twelve hours, 1a and 1b both inactivate the enzyme by 40%. Copyright (C) 1996 Elsevier Science Ltd.