Molecular structures of two 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 transgauche+ 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) A, 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.
Liaw
Y C
YC
Department of Physiology & Biophysics, University of Illinois, Urbana 61801.
Gao
Y G
YG
Marquez
V E
VE
Wang
A H
AH
D000998:Antiviral Agents / Q000737:chemistry*; D016049:Didanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D016048:Dideoxyadenosine / Q000031:analogs & derivatives* / Q000737:chemistry; D015224:Dideoxynucleosides / Q000737:chemistry*; D006678:HIV / Q000187:drug effects*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D000998:Antiviral Agents; D015224:Dideoxynucleosides; C073075:9-(2,3-dideoxy-2-fluoro-betaD-threo-pentofuranosyl)hypoxanthine; C073072:lodenosine; D016048:Dideoxyadenosine; D016049:Didanosine