ChemInform Abstract: Structure of RG-12561 Dichloromethane Solvate and a Diastereomer.

Abstract

(III): [4 alpha,6 beta(E)]-(+-)-6-(2-[2-(4-Fluoro-3-methylphenyl)- 4,4,6,6-tetramethyl-1-cyclohexen-1-yl]ethenyl)-4-hydroxytetrahy dro pyran-2-one (RG-12561) dichloromethane solvate, 2C24H31FO3.CH2-Cl2, Mr = 857.94, triclinic, Pl, a = 11.7413 (5), b = 13.0279 (5), c = 16.2332 (9) A, alpha = 99.456 (4), beta = 94.217 (4), gamma = 101.893 (4) degrees, V = 2381.9 (4) A3, Z = 4 [four molecules of (III)+two molecules of solvent per unit cell], Dx = 1.195 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 16.69 cm-1, F(000) = 912, T = 293 K, final R = 0.053, wR = 0.060 for 4031 reflections with I greater than 3 sigma(I). (IV): [4 beta,6 alpha(E)]-(+-)-6-(2-[2- (4-Fluoro-3-methylphenyl)-4,4,6,6-tetramethyl-1-cyclo-hexen-1-yl]e thenyl)-4- hydroxytetrahydropyran-2-one, C24H31FO3, Mr = 386.51, triclinic, Pl, a = 6.054 (2), b = 12.931 (2), c = 14.838 (3) A, alpha = 67.70 (2), beta = 85.75 (2), gamma = 82.85 (2) degrees, V = 1066.0 (8) A3, Z = 2, Dx = 1.203 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 6.86 cm-1, F(000) = 414, T = 293 K, final R = 0.073, wR = 0.081 for 1588 reflections with I greater than 3 sigma(I). (III) is a potent HMG-CoA reductase inhibitor and has the potential to function as a superior hypocholesterolemic agent; (IV) lacks this activity. (III) and (IV) have different conformations and molecular-model calculations suggest that crystal-packing effects are primarily responsible for the overall conformation of (IV). The principal intermolecular contacts are hydrogen bonds of the type O-H...O = C.