SOME NOVEL NUCLEOSIDE REARRANGEMENTS EFFECTED BY (DIETHYLAMINO)SULPHUR TRIFLUORIDE - SYNTHESIS AND ANTIVIRAL PROPERTIES OF SOME FLUORINE-CONTAINING 3'-AZIDO-3'-DEOXYTHYMIDINE DERIVATIVES

The reaction of pyrimidine nucleoside 5'-aldehydes with (diethylamino) sulphur trifluoride (DAST) to produce 5'-deoxy-5',5'-difluoronucleosid es is reported. The preferred reaction is the production of the O2,5'- anhydro-5'-fluoronucleoside. If this is prevented by substitution at O 4 or N-3 then, in the former case, either DAST no longer reacts or und er 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 latt er case, the 5'-aldehyde of 2',3'-O-isopropylideneuridine gives the 5' -deoxy-5',5'-difluoro compound as the sole identifiable product. With the 5'-aldehyde of AZT [suitably protected at N-31 as starting materia l, 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 immunodefi ciency virus type-1 (HIV-1) at concentrations up to 100 muM.