FARNESYL AND GERANYLGERANYL PYROPHOSPHATE ANALOGS INCORPORATING BENZOYLBENZYL ETHERS - SYNTHESIS AND INHIBITION OF YEAST PROTEIN FARNESYLTRANSFERASE

The syntheses of two photoactive analogs (1a and 1b) of farnesyl pyrop hosphate that incorporate stable ether-linked benzophenones are descri bed. Compounds 1a and 1b were prepared from geraniol in 17% overall yi eld. Both 1a and 1b are competitive inhibitors of yeast protein farnes yltransferase with respect to farnesyl pyrophosphate and have K-I valu es of 45 nM and 49 nM. Upon photolysis for twelve hours, 1a and 1b bot h inactivate the enzyme by 40%. Copyright (C) 1996 Elsevier Science Lt d.