Various reverse transcriptase inhibitors have been found to be effective in inhibiting HIV reverse transcriptase. Amongst the more effective such inhibitors are 3'-deoxy-3'-azidothymidine (AZT), 2',3'-dideoxycytidine (ddC) and 2',3'-dideoxy-inosine (ddI).
A number of fluorinated 2',3'-dideoxynucleosides have been prepared in order to seek out biologically active and chemically stable agents that effectively inhibit HIV reverse transcriptase. Two very important fluorodideoxy nucleotides that function as HIV reverse transcriptase inhibitors are 9-(2,3-dideoxy-2-fluoro-.beta.-D-threo-pentofuranosyl)-adenine (FddA) and 1-(2,3-dideoxy-2-fluoro-.beta.-D-threo-pentofuranosyl) cytosine (FddC).
Since FddA is a promising candidate for the treatment of AIDS, various synthetic pathways have been tried to synthesize FddA. These processes are, however, expensive and there continues to be a need for a more economical procedure.
Okabe et al (J. Org. Chem. 1991,56,4392) have produced (S,S)-.alpha.-fluoro-2,2-dimethyl-1,3-dioxolane-4-propanoic acid methyl ester having the formula (I): ##STR1## as a key intermediate for the synthesis of FddC. The Okabe et al synthesis of (I) begins with the inexpensive sugar D-xylose. However, the introduction of fluorine in the Okabe et al. synthesis was performed by leaving group displacement with fluoride ion which caused a loss of stereochemical control. This led to the formation of a mixture of diastereoisomers that required enrichment of the desired diastereoisomer by chemical or enzymatic means.
Since intermediate of formula (I) can be used to prepare both FddC and FddA, there remains a continuing need for a more efficient synthetic route to this intermediate in which there is essentially complete stereochemical control.