1,2,4-DIAZAPHOSPHOLE NUCLEOSIDES - SYNTHESIS, STRUCTURE, AND ANTITUMOR-ACTIVITY OF NUCLEOSIDES WITH A LAMBDA-3 PHOSPHORUS ATOM

Glycosylation of 1, 2, 4 λ3-diazaphosphole (4) under Lewis acid catalyzed conditions gave 1-α-D-ribofuranosyl-1, 2, 4 λ3diazaphosphole (5) as the only product. Ethyl 1, 2, 4 λ3diazaphosphole-3-carboxylate (10) was synthesized by the cyclocondensation of ethyl (chlorophosphinidene)(trimethylsilyl)acetate (8) with (trimethylsilyl)diazomethane and subsequent desilylation with tetra-n-butylammonium fluoride. Reaction of 10 with methanolic ammonia at 80 °C gave 1,2, 4 λ3-diazaphosphole-3-carboxamide. Glycosylation of 10 using trimethylsilyl triflate catalyst followed by ammonolysis gave the ribavirin (1) analogue 1-β-D-ribofuranosyl-1, 2, 4 λ3-diazaphosphole-3-carboxamide (11). Acetylation of 11 and subsequent treatment with phosphorus pentasulfide gave 2',3',5'-tri-O-acetyl-l-β-D-ribofuranosyl-1, 2, 4 λ3-diazaphosphole-3-thiocarboxamide (13). Deprotection with methanolic ammonia gave 1-β-D-ribofuranosyl-1, 2, 4 λ3-diazaphosphole-3-thiocarboxamide (14). Compound 14 gave a 25% increase in life span (ILS) against L1210 in female BDF1mice. The anomeric configuration and site of glycosylation of 5 and 13 were established by single-crystal X-ray crystallography. © 1990, American Chemical Society. All rights reserved.