Synthesis of 1-deaza-6-thioguanosine and 1-deaza-6-(methylthio)guanosine.
A synthesis of 1-deaza-6-thioguanosine (8) and 1-deaza-6-(methylthio)guanosine (9) from 2-amino-6-chloro-1-deazapurine (4) is described. The reaction of the N2-acetyl derivative of 4 with 2,3,5-tri-O-acetyl-D-ribofuranosyl chloride in the presence of Linde 4A molecular sieve gave the blocked nucleoside 6. Deacetylation of 6 gave the chloro nucleoside 7 which was treated at high temperature with hydrogen sulfide and methyl mercaptan to give 8 and 9, respectively. The structure of 7 was confirmed by 1H NMR and by conversion to the cyclonucleoside 14. Compound 4 gave a 79% increase in life span in the L1210 mouse leukemia screen.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006151:Guanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D013872:Thionucleosides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D013872:Thionucleosides; D006151:Guanosine