SOLUTION CONFORMATION OF THE ANTI-HIV-ACTIVE COMPOUND (S,S)-ISODIDEOXYADENOSINE

In the design of novel dideoxynucleosides with anti-HIV activity, a va riety of structure-activity correlations are being investigated, inclu ding the correlation of activity with conformation of the active compo unds in solution, Using multiple 1-D and 2-D NMR techniques and comput ational analyses, the preferred conformation in solution of the anti-H IV active compound (S,S)-isodideoxyadenosine was determined. These stu dies showed that there are two preferred conformations of the carbohyd rate moiety in solution. Almost 58% of the population is In the northe rn conformation (P = -43.3 degrees, T-1(2)) of the pseudo-rotation cyc le 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 st udies confirmed the anti conformation of the base about the 'glycosidi c' bond and gave information on the orientation of the hydroxymethyl g roup [p gamma(+) = 0.49 (gg) with the remaining 51% being part gamma t (ap) and part gamma].