Structures of 5-bromo-6-ethoxy-5,6-dihydrouridine and -thymidine derivatives, a class of potential antitumoral and antiviral N-nucleosides.
(I): (+)-(5R,6R)-5-Bromo-6-ethoxy-5,6-dihydro-2',3'-isopropylidene-beta-D- ribofuranosyl-uracil, C14H21BrN2O7, m.p. 408.7-409.6 K, [alpha]D23 degrees C = +31.1 degrees (c = 1.2% in MeOH), Mr = 409.2, monoclinic, P2(1), a = 9.218 (2), b = 9.6619(11) c = 10.4938 (14) A, beta = 99.305 (8) degrees, V = 922.4 (2) A3, Z = 2, Dx = 1.47 Mgm-3, lambda (Mo K alpha) = 0.71069 A, mu = 2.24 mm-1, F(000) = 420, room temperature, R (= wR) = 0.046 for 2595 observed reflections [(Fo)] greater than 4 sigma (Fo) and (Fo) greater than 8.0]. (II): (+)-(5R,6R)-5-Bromo-2'-deoxy-6-ethoxy-5,6-dihydro-beta-D-ribofuranosyl- thymine, C12H19BrN2O6, m.p. 376.1-376.5 K, [alpha]D 23 degrees C = + 58.8 degrees (c = 1.02% in MeOH), Mr = 367.2, monoclinic, clinic, P21, a = 6.0428 (9), b = 8.5270 (15), c = 14.589 (2) A, beta = 96.80 (1) degrees, V = 746.4 (1) A3, Z = 2, Dx = 1.63 Mg m-3, lambda(Mo K alpha) = 0.71069 A, mu = 2.75 mm-1, F(000) = 376, room temperature, R = 0.053 (wR = 0.040) for 1579 observed reflections [[F0[ less than 4 sigma(Fo)]. Both furanose rings adopt an envelope conformation with C(4')-exo and C(1')-exo for (I) and (II) respectively. The orientation of the dihydropyrimidine base relative to the sugar ring shows an unusual syn conformation [chi CN = 62.5 (6) degrees] for (I) whereas the glycosyl linkage of compound (II) shows an anti conformation [chi CN = -134.0 (8) degrees]. In both compounds the pyrimidine ring displays a half-chair form. The conformation of the hydroxymethyl group at C(4') is gauche-gauche for (I) [phi OO = -68.2 (7) degrees, phi OC = 50.1 (8) degrees] and trans-gauche for (II) [phi OO = 180 (1) degrees, phi OC = -61 (1) degrees]. The absolute configuration of (I) was confirmed by least-squares refinement of x [x = 0.008 (16)] [Bernardinelli & Flack (1985). Acta Cryst. A41, 500-511] and that of compound (II) deduced from the starting material. An intramolecular hydrogen bond occurs between the hydroxymethyl and the pyrimidine of (I). In both structures, the molecular packing is fixed by a network of hydrogen bonds.
Bernardinelli
G
G
Laboratoire de Cristallographie aux rayons X, Université de Genève, Switzerland.
Benhamza
R
R
Tronchet
J M
JM
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D013936:Thymidine / Q000031:analogs & derivatives*; D014529:Uridine / Q000031:analogs & derivatives*; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; D000998:Antiviral Agents; C064024:5-bromo-6-ethoxy-5,6-dihydro-2',3'-isopropylidine-beta-ribofuranosyluracil; C064025:5-bromo-2'-deoxy-6-ethoxy-5,6-dihydro-beta-ribofuranosylthymine; D013936:Thymidine; D014529:Uridine