Some novel nucleoside rearrangements effected by (diethylamino)sulphur trifluoride: synthesis and antiviral properties of some fluorine-containing 3'-azido-3'-deoxythymidine derivatives

Article abstract of DOI:10.1016/S0022-1139(00)80089-5

The reaction of pyrimidine nucleoside 5'-aldehydes with (diethylamino)sulphur trifluoride (DAST) to produce 5'-deoxy-5',5'-difluoronucleosides is reported.The preferred reaction is the production of the O²,5'-anhydro-5'-fluoronucleoside.If this is prevented by substitution at O⁴ or N-3 then, in the former case, either DAST no longer reacts or under drastic conditions the C(1')-N(1) bond breaks and the heterocyclic base remains joined by C-5' <*> O² to a glycosyl fluoride.In the latter case, the 5'-aldehyde of 2',3'-O-isopropylideneneuridine gives the 5'-deoxy-5',5'-difluoro compound as the sole identifiable product.With the 5'-aldehyde of AZT as starting material, treatment with DAST yields a diastereoisomeric mixture of glycosyl fluorides and a derivative of 5'-deoxy-5',5'-difluoro AZT from which 3'-azido-3',5'-dideoxy-5',5'-difluorothymidine could be isolated.This compound is not toxic nor has it any activity against human immunodeficiency virus type-1 (HIV-1) at concentrations up to 100 μM.