MOLECULAR-STRUCTURES OF 2 NEW ANTI-HIV NUCLEOSIDE ANALOGS - 9-(2,3-DIDEOXY-2-FLUORO-BETA-D-THREO-PENTOFURANOSYL)ADENINE AND 9-(2,3-DIDEOXY-2-FLUORO-BETA-D-THREO-PENTOFURANOSYL)HYPOXANTHINE

The x-ray crystal structures of two new anti-HIV compounds, 9-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl) adenine (2'-F-dd-araA) and 9-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl) hypoxanthine (2'-F-dd-aral), have been determined at 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 final 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 conformers (one for 2'-F-dd-araA and two for 2'-F-dd-aral) adopt an anti(chi)CN glycosyl torsion angle. The sugar in the 2'-F-dd-araA structure has a C2-endo pucker conformation, whereas the sugar in the 2'-F-dd-aral 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'-C5' bond is in a trans-gauche+ conformation. In 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 1.406(3) angstrom, similar to that found in other aliphatic C-F bonds. The results suggest that the 2'-fluoro-2',3'-dideoxyarabinosyl nucleosides do not have a strong preference for either C2-endo or C3'-endo sugar pucker.