Synthesis of deoxy phosphatidylinositol analogues and phosphonate isostersof Ins(1,4,5)P-3

The synthesis of phosphatidylinositol analogues, 6-deoxy Ins 1-(1,2-di-O-pa lmitoyl-sn-glycero)phosphate and 4,5-bisphosphate derivatives is presented. Two series of phosphonate isosters, 6-deoxy Ins(1)-butylphosphonate and 6- deoxy Ins(1)-C-methylenephosphonate as well as its 4,5-bisphosphate analogu e were also prepared. All phosphoinositide analogues were obtained from cyc lohexanone polyol derived from the D-galactose. Modification of charge dist ribution at position 1 of PtdIns and InsP derivatives, by replacement of a P-OH group lay an alkyl substitution or a P-C bond, resistant to cleavage b y lipases, could induce inhibition of activity at further strategic enzymat ic levels of the inositide cascade, (C) 1999 Elsevier Science Ltd. All righ ts reserved.