Inhibition of the strand transfer step of HIV-1 integrase by non-natural dinucleotides

New, non-natural dinucleotide 5′-monophosphates, with a surrogate isonucleoside component of l-related stereochemistry at the ‘terminal’ position, have been synthesized. Structures of 2a–c were confirmed by multinuclear NMR spectra (1H, 13C, 31P, COSY), UV hypochromicity and FAB HRMS data. These compounds are totally resistant to cleavage by 3′- and 5′-exonucleases. The dinucleotides 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 selective strand transfer inhibitors of HIV integrase.