Solution conformation of the anti-HIV-active compound (S,S)-isodideoxyadenosine

In the design of novel dideoxynucleosides with anti-HIV activity, a variety of structure-activity correlations are being investigated, including the correlation of activity with conformation of the active compounds in solution, Using multiple 1-D and 2-D NMR techniques and computational analyses, the preferred conformation in solution of the anti-HIV active compound (S,S)-isodideoxyadenosine was determined. These studies showed that there are two preferred conformations of the carbohydrate moiety in solution. Almost 58% of the population is In the northern conformation (P = -43.3 degrees, T-1(2)) of the pseudo-rotation cycle and 42% is in the southern hemisphere (P = 197.9 degrees,(3)E). The x-ray crystallographic data showed that the compound crystallized out in the T-o(1) conformation (P = 108 degrees). In addition, the NMR studies confirmed the anti conformation of the base about the 'glycosidic' bond and gave information on the orientation of the hydroxymethyl group [p gamma(+) = 0.49 (gg) with the remaining 51% being part gamma t(ap) and part gamma].