Molecular structures of two new anti-HIV nucleoside analogs: 9-(2,3-dideoxy-2-fluore-β-D-threopentofuranosyl)adenine and 9-(2,3-dideoxy-2-fluoro-β-D-threo-pentofurancsyl)hypoxanthine

Abstract

The x-ray crystal structures off two new anfi-HIV compounds, 9-(2,3-dideoxy-2-fluoro-β-D- threo -pento-furanosyl,adenine (2'-F-dd-araA) and 9-(2,3-dideoxy-2-fluoro-β-D- threo -pentofuranosyl)hypoxanthine (2'-F-dd-aral), have been determined aft two temperatures. Both crystals are in the space group P2 1 2 1 2 1 , and their structures were solved by direct methods. Least-squares refinement produced kintal R-factors of 0.027 for the 2'-F-dd-araA structure and of 0.044 for the 2'-F-dd-aral structure, respectively. The latter structure contains a two-fold disordered conformation of the sugar moiety. All three conformmers (one for 2'-F-dd-araA and two for 2'-F-dd-aral) adopt an anti xCN glycosyl torsion angle. The sugar in the 2'-F-dd-araA structure has a C2' -endo pucker conformatioin), whereas the sugar in the 2'-F-dd-araO structure has a mixture of C2' -endo and C3' -endo pucker conformations. When the sugar adopts the C2' -endo conformation, the torsion angle about the C4'-G5' bond is in a transgauche + -conformation. On contrast, when the sugar adopts the C3'-endo conformation, the torsion angle about the C4'-C5' bond is in a gauche + -gauche − conformation. The C2'-F bond distance is 1.403(3) A, similar to that found in other aliphatic C-F bonds. The results suggest that the 2'-fluoro-2', 3'-dideoxyarabino-syl nucleosides do not have a strong preference for either C2' -endo or C3 -endo sugar pucker.