SYNTHESIS OF PHOSPHONATE ANALOGS OF CMP-NEU5AC DETERMINATION OF ALPHA(2-6)-SIALYLTRANSFERASE INHIBITION

Treatment of sialyl phosphites with TMSOTf as catalyst affords alpha-a nd beta-sialyl phosphonates. This phospshite/phosphonate-exchange reac tion was employed for the synthesis of sialylphosphonate dialkyl ester s 5a alpha-5c alpha and 58 beta-5c beta. Monodemethylation of 5c alpha and 5c beta, linkage to 5'-O-unprotected cytidine derivative 7, and t hen deprotection furnished the phosphonate analogue 2 beta of CMP-Neu5 Ac and the corresponding alpha-isomer 2 alpha, respectively. Their str uctures could be assigned and inhibition of alpha(2-6)-sialyltransfera se was determined. (C) 1998 Elsevier Science Ltd. All rights reserved.