STRUCTURE OF 4-PYRIDYL)-CARBAMOYL]-9A-AZA-9A-HOMOERYTHROMYCIN-A AND CONFORMATIONAL-ANALYSIS OF ANALOGOUS 9A-AZA 15-MEMBERED AZALIDES IN THESOLID-STATE

C43H74N4O13.C3H6O, M(r) = 913, triclinic, P1, a = 10.3796 (5), b = 14. 5809 (5), c = 17.1521 (9)Angstrom, alpha = 105.225 (3), beta = 96.140 (5), gamma = 90.248 (3)degrees, V = 2489.0 (2)Angstrom(3), Z = 2 (two independent molecules in the asymmetric unit), D-x = 1.218 g cm(-3), l ambda(CuK alpha) = 1.54184 Angstrom, T = 106 (3)K, F(000) = 992, mu(Cu K alpha) = 7.0 CM(-1), R = 0.057 for 8724 observed unique reflections with I > 2 sigma(I). Conformational analysis is based on X-ray structu re determinations of 9-deoxo-9a-N-[N'-(4-pyridyl)-carbamoyl] -9a-aza-9 a-homoerythromycin A (1) and its N-isopropyl-carbamoyl congener (2) an d data for 9a-aza 15-membered azalides retrieved from the Cambridge St ructure Database (Version 5.07). The analysis reveals that the aglycon e ring conformation has been influenced by the presence or absence of glyco conjugation at C3 and C5 sites in azalide derivatives. However, more drastic influence is related to the appearance of intramolecular hydrogen bonds. Compounds with 9a N atoms in sp(3) hybridization exhib it N-H ... O contacts which are absent in compounds with 9a N atoms in sp(2) hybridization: they reveal O-H ... O intramolecular hydrogen bo nds. The 15-membered azalides studied are in 'folded-out' conformation in the solid state. The alpha-L-cladinose sugar moiety is in C-1(4) c onformation, while the beta-D-desosamine adopts a C-4(1) conformation. The absolute configurations at the aglycone chiral centres are as fol lows: C2R, C3S, C4S, C5R, C6R, C8R, C10R, C11R, C12S and C13R.