SYNTHESIS AND BIOLOGICAL-ACTIVITIES OF (4,6-DI-O-PHOSPHONATO-BETA-D-MANNOPYRANOSYL)-METHYLPHOSPHONATE AS AN ANALOG OF 1L-MYO-INOSITOL 1,4,5-TRISPHOSPHATE

The synthesis of the alpha and beta anomers of the title compound (1) was accomplished from D-mannose. In the key step, the phosphonate analogues of the mannopyranosyl phosphates were prepared by a direct Wadsworth-Emmons condensation of a protected mannose derivative (8) with tetraethyl methylenebisphosphonate under two-phase conditions. In vitro bioassays have shown that the beta anomer (1a> is a potent inhibitor of Ins(1,4,5)P-3 3-kinase and inhibits other enzymes.