Search

The role of the base in the synthesis of 3′-deoxy-3′-[18F]fluorothymidine, [18F]FLT, via nucleophilic substitution of the nosyl group with [18F]fluoride was investigated. The rate of 18F-incorporation into the molecule dramatically changed as a function of the precursor-to-base ratio. In the presence of excess base, the precursor was consumed by elimination before substitution was complete. When the precursor-to-base ratio was optimal, an overall [18F]FLT yield of 30–40% was achieved even if the precursor amount was as small as 8–13 mg.

A series of pro-nucleotide phosphoramidates and phosphorodiamidates of the antiviral lead compound 3′-deoxy-3′-fluorothymidine (FLT) have been designed and synthesized. In vitro antiretroviral and cytostatic studies revealed potent (sub-micromolar) inhibition of HIV-1 and HIV-2 replication, with retention of activity in thymidine kinase-negative cell models, as predicted by the ProTide concept.

The use of methyl 5-0- tert -butyldiphenylsilyl-2-deoxy-α , β -D- threo -pentofuranoside, prepared from D-xylose,as a divergent intermediate for the synthesis of 3'-substituted-2',3'-dideoxynucleosides is illustrated by its conversion into 3'-azido-3'-deoxythymidine, 3'-deoxy-3'-fluorothymidine and 3'-cyano-3'-deoxythymidine.