SYNTHESIS, ANTIRETROVIRUS EFFECTS, AND PHOSPHORYLATION KINETICS OF 3'-ISOCYANO-3'-DEOXYTHYMIDINE AND 3'-ISOCYANO-2',3'-DIDEOXYURIDINE

The silylated AzddThd 5 and AzddUrd 6 prepared from 2,3'-anhydronucleoside derivatives 3 and 4 were transformed to formamides 7 and 8 by using the sequence RN3→ RN=P(C6H5)→ RNHCHO. Formamides 7 and 8 were dehydrated to the protected 3'-isocyano derivatives 9 and 10; deblocking gave 11 and 12. Neither 3'-isocyano-3'-deoxythymidine (11) nor 3'-isocyano-2',3'-dideoxyuridine (12) showed anti-HIV activity at noncytotoxic concentrations. ddThd derivative 11 was considerably more toxic to MT-4 cells than ddUrd derivative 12; it also had a much greater affinity (K)ifor MT-4 cell dThd kinase than ddUrd derivative 12. Both compounds appear to be linear mixed-type inhibitors of MT-4 cell dThd kinase. © 1990, American Chemical Society. All rights reserved.