Synthesis of branched-chain apiosylpyrimidines and their inhibition of lymphocyte proliferation

Abstract

Branched-chain nucleosides containing beta-D-apio-L-furanose were synthesized by condensation of the bis(trimethylsiyl) derivative of uracil (11), thymine (12), 5-fromouracil (13), and 5-iodouracil (14) with the protected 1-O-acetylapiose in the presence of a Friedel-Crafts catalyst. D-Apio-L-furanosyluracil (11) and D-apio-L-furanosylthymine (12) show immunosuppressive activity for rat T-lymphocytes stimulated to grow by phytohemagglutinin but exhibit no inhibitory activity against herpes simplex virus. Compounds 11--14 did not inhibit herpes simplex virus replication, while low inhibition was obtained with the one nucleoside containing D-apio-D-furanose, D-apio-D-furanosyladenine. D-Apio-L-furanosyl-5-bromouracil (13), D-apio-L-furanosyl-5-iodouracil (14), bromouridine, and iodouridine suppressed growth of human lymphoblasts significantly more than the nonhalogenated apiosylphrimidines.