THE SYNTHESIS AND BIOPHYSICAL INVESTIGATIONS OF NOVEL RING-EXPANDED NUCLEOSIDES, NUCLEOTIDES, AND HOMOPOLYMERS CONTAINING THE 5-7-FUSED HETEROCYCLIC RING-SYSTEM IMIDAZO[4,5-E][1,4]DIAZEPINE

The synthesis and conformational studies of two isomeric 5:7-fused nucleosides, 4,5,7,8-tetrahydro-6H-3-(β-D-ribofuranosyl)imidazo[4,5-e][1,4]diazepine-5,8-dione (1) and its 1-glycosyl analogue (2), their respective 5’-mono-and -diphosphate derivatives (13 and 14), and the corresponding homopolymers (15 and 16) are presented. While 1 is devoid of activity against murine leukemia virus (MuLV) in tissue culture systems, 2 is as active as interferon. Nucleoside 1 exhibits a predominantly syn base-ribose conformation both in solid state and solution. The conformation of 2, by contrast, is anti in both phases. The sugar pucker geometry in 1 is C2’_endo-C3.exo, whereas that in 2 is the opposite C2.eio-C3.endo. The 5’-diphosphate derivative of the anti conformer (14c) undergoes polymerization with E. coli polynucleotide phosphorylase with ease, and the resultant homopolymer 16 reveals considerable internal secondary structure with a stable helical conformation. The corresponding observations on the syn conformer are strikingly opposite. © 1990, American Chemical Society. All rights reserved.