MAIN-PART ISOSTRUCTURALISM OF SEVERAL CARDENOLIDES AND BUFADIENOLIDES - STRUCTURES OF 3 CARDENOLIDES - (21S)-METHYLDIGITOXIGENIN, UZARIGENIN AND SARMENTOGENIN METHANOL SOLVATE

'Main-part' isostructuralism is a recurrent phenomenon among cardiotonic steriods. Here (21S)-methyldigitoxigenin is found to be isostructural with digitoxigenin [and with 3-epi-digitoxigenin, (21R)-methyldigitoxigenin and digirezigenin], a fact which allowed the structure amplitudes to be phased using the position of 21 non-H atoms of the 14-isoaethiocholane skeleton. The limits of the phenomenon have been studied by a structure analysis of uzarigenin which differs from digitoxigenin only in its A/B ring junction but which exhibits a fundamentally different type of packing. Besides the different position of ring A, this may also be attributed to the different degree of rotation (DELTA-psi congruent-to 180-degrees) of the gamma-lactone ring about the C(17)-C(20) bond. The earlier observation that the two energetically favourable conformations of the gamma-lactone moiety may occur in the cardenolide structures with almost the same probability is supported by the fact that the crystal of the 1:1 sarmentogenin-methanol adduct contains both conformers, each of which was found either in digitoxigenin or in uzarigenin. These facts help to clarify the conditions and restrictions of isostructuralism not only among digitoxigenin and its derivatives but also between several pairs of analogous bufadienolides. (21S)-Methyldigitoxigenin [(21S)-3-beta,14-dihydroxy-21-methyl-5-beta, 14-beta-card-20(22)-enolide], C24H36O4, M(r) = 388.55, orthorhombic, P2(1)2(1)2(1), a = 7.193 (1), b = 15.208 (3), c = 19.277 (4) angstrom, V = 2108.8 (9) angstrom3, Z = 4, D(x) = 1.224 g cm-3, lambda(Mo K-alpha) = 0.71073 angstrom, mu = 0.76 cm-1, F(000) = 848, R = 0.049 for 1754 unique observed reflections. Uzarigenin [3-beta,14-dihydroxy-5-alpha, 14-beta-card-20(22)-enolide], C23H34O4, M(r) = 374.53, monoclinic, P2(1), a = 6.370 (3), b = 12.072 (4), c = 13.024 (3) angstrom, beta = 99.87 (3)-degrees, V = 986.7 (1.1) angstrom3, Z = 2, D(x) = 1.261 g cm-3, lambda(Mo K-alpha) = 071073 angstrom, mu = 0.79 cm-1, F(000) = 408, R = 0.040 for 1950 unique observed reflections. Sarmentogenin [3-beta,11-alpha, 14-trihydroxy-5-beta,14-beta-card-20(22)-enolide] methanol solvate, C23H34O5.CH3OH, M(r) = 442.57, orthorhombic, P2(1)2(1)2(1), a = 16.678 (5), b = 13.332 (4), c = 10.063 (3) angstrom, V = 2238 (2) angstrom3, Z = 4, D(x) = 1.254 g cm-3 lambda(Mo K-alpha) = 0.71073 angstrom, mu = 0.83 cm-1, F(000) = 920, R = 0.051 for 1840 unique observed reflections.