Synthetic Approaches to Nuclease-Resistant,Nonnatural Dinucleotides of Anti-Hiv Integrase Interest

New, nonnatural dinucleotide 5′-monophosphates with a surrogate isonucleoside component of L-related stereochemistry, have been synthesized. Structures of the target compounds were confirmed by multinuclear NMR spectra (¹H, ¹³C, ³¹P, COSY), UV hypochromicity, FAB HRMS data and X-ray crystallography. These compounds are totally resistant to cleavage by 3′- and 5′-exonucleases. Dinucleotides of this study with a terminal L-isonucleoside component showed remarkable selectivity for inhibition of the strand transfer step of HIV-1 integrase. To the best of our knowledge, these compounds represent only the second example of this type of selectivity of inhibition of the strand transfer step.