Solution Conformation of the Anti-HIV-Active Compound (S,S)-Isodideoxyadenosine

✍ Scribed by Pascal J. Bolon; Vasu Nair

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 448 KB
• Volume: 34
• Category: Article
• ISSN: 0749-1581
• DOI: 10.1002/(sici)1097-458x(199604)34:4<243::aid-omr865>3.0.co;2-c

✦ Synopsis

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", 'TZ) of the pseudo-rotation cycle and 42% is in the southern hemisphere (P = 197.9", &. The x-ray crystallographic data showed that the compound crystallized out in the YT conformation (P = 108"). 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 [py' = 0.49 (gg) with the remaining 51% being part yt(ap) and part y].