Synthesis of branched-chain apiosylpyrimidines and their inhibition of lymphocyte proliferation.
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.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D037102:Lectins / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008938:Mitosis / Q000187:drug effects; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D018139:Simplexvirus / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D013936:Thymidine / Q000097:blood; D010948:Viral Plaque Assay
D037102:Lectins; D011743:Pyrimidines; D004247:DNA; D013936:Thymidine