Stereoselective preparation of protected thymine polyoxin C and approachestowards synthesis of its C2 '-modified analogues

Polyoxins form an important class of pyrimidine peptide antifungal agents. The preparation of thymine polyoxin C, which is the nucleosidic component o f some polyoxins, is reported, together with attempts to synthesize C2'-flu oro analogues. Epimeric 3-hydroxyazidolactones 2a and 2b, obtained from dia stereoisomeric epoxy hydroxy esters, were dehydrated to afford butenolide 3 . Dihydroxylation and further functional manipulation yielded thymine polyo xin C. Attempts to form the 2,2'-anhydronucleoside and to direct nucleophil ic fluorination with DAST on a monoprotected nucleoside were unsuccessful. Electrophilic fluorination of azidolactone with NFSI permitted the formatio n of an alpha -fluorolactone, which is an interesting intermediate for the preparation of a C2'-fluoro analogue.