SYNTHETIC APPROACHES TO NEW DOUBLY MODIFIED NUCLEOSIDES - CONGENERS OF CORDYCEPIN AND RELATED 2'-DEOXYADENOSINE

The syntheses of novel analogues of cordycepin (compounds 20-25) and 2'-deoxyadenosine (compounds 11, 13-15, 18, 19) are reported. In order to obtain entry into both the 3'-deoxy and 2'-deoxy isomeric series from a common starting compound, 2-amino-6-chloropurine ribonucleoside, this precursor was protected by conversion to a mixture of 2',5'- and 3',5'-bis-silyl compounds prior to modifications at the 2'- or 3'-positions of the carbohydrate moiety and the 2-position of the base component. Observation of silyl group isomerization is discussed. The other key transformations in the syntheses were radical deoxygenations (carbohydrate moiety), radical iodinations (tailoring of base for modification), and metal-mediated functionalization reactions (regio-specific modifications of base component). Structures of the final target molecules and their purities were established by UV, high-field H-1 and C-13 NMR, and FAB HRMS data. The synthetic approaches presented have generality and provide entry into a variety of doubly modified nucleosides.