Simvastatin

Abstract

Simvastatin, or (1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxo-3,4,5,6-tetrahydro-2H-pyran-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2,2-dimethylbutanoate, C(25)H(38)O(5), is almost isostructural with lovastatin, and the general conformational features are closely related to those of other reported crystal structures of statins. The only hydrogen bond present facilitates the formation of infinite chains of molecules along the b axis.

Simvastatin: structure solution of two new low-temperature phases from synchrotron powder diffraction and ss-NMR

“…Below the second transition temperature (273 K) the recorded 13 C NMR signals did not exhibit significant temperature dependences and the existence of two sets of NMR signals indicates presence of two symmetry independent molecules in the crystal unit (molecules 1 and 2, Form III). From our previous investigations of simvastatin [1,5] followed that the ester tail undergoes extensive dynamic disorder. Fast jumps or rotational diffusion motions around the axis defined by carbon atoms C20-C21 and C21-C22 occur at room temperature.…”

“…The crystal structure of the well-known simvastatin Form I was previously reported [1]. The changes indicating occurrence of two new phases (II and III) were observed in the course of the preliminary ss-NMR experiments at low temperatures.…”

“…The system of the H-bond is in all phases identical as already described in [1]. The packing is based on only one hydrogen bond O3-HÁÁÁO5(1 -x, y ?…”

“…The indexation of phase III indicated change from orthorhombic to monoclinic system and change from P2 1 2 1 2 1 space group to P2 1 group. Even in this case it was possible to derive enough good starting model form the phase I by Scheme 1 Structure of simvastatin with the atom numbering as used in [1] making two molecules in asymmetric unit cell to refine independently. The phase I shows a disorder in the side chains.…”

“…Crystal data from single crystal measurement of phase I taken from[1] and powder diffraction measurement of phases I-III…”