617-41-4Relevant articles and documents
Asymmetric Synthesis of Atorvastatin Calcium through Intramolecular Oxidative Oxygen-Nucleophilic Bromocyclization
Wu, Yan,Liu, Min-Jie,Huang, Hai-Qing,Huang, Guan-Xin,Xiong, Fang-Jun,Chen, Fen-Er
, p. 3681 - 3688 (2017/07/22)
The stereocontrolled synthesis of atorvastatin calcium starting from commercially available d-aspartic acid using an intramolecular oxidative oxygen-nucleophilic bromocyclization of a homoallylic tert-butyl carbonate is described. This strategy allows the formation of the chiral syn-1,3-diol moiety with the desired stereochemistry, and provides a functionalized bromomethyl group for the construction of the atorvastatin side-chain with high regio- and diastereoselectivity. This route is attractive as it represents an efficient and environmentally sensitive approach to the large-scale synthesis of statins and their analogues.
Accessing Centnerszwer's quasiracemate-molecular shape controlled molecular recognition
Spaniol, Jacqueline M.,Wheeler, Kraig A.
, p. 64921 - 64929 (2016/07/21)
M. Centnerszwer's seminal 1899 report investigated the stereochemical relationship between optical antipodes of different substances using melting-point behavior. One intriguing melting-point phase diagram produced from this early investigation combined (+)-2-chlorosuccinic acid [(+)-1] and (-)-2-bromosuccinic acid [(-)-2]. While Centnerszwer's data clearly indicates the formation of a quasiracemic phase-i.e., materials constructed from pairs of isosteric molecules of opposite handedness-at the 1:1 component ratio, this material is energetically less favorable than the chiral counterparts. The consequence of this crystal instability is significant as evident by the absence of literature sited crystal structures for the quasiracemic phase (+)-1/(-)-2 and racemates (±)-1 and (±)-2. This study circumvented this challenge by generating multi-molecular assemblies using additional crystallizing agents capable of complementing the hydrogen-bond abilities of succinic acids 1 and 2. Both imidazole (Im) and 4,4′-bipyridyl-N,N′-dioxide (BPDO) served as tailor-made additives that effectively modified the crystal packing landscape of quasiracemate of (+)-1/(-)-2. Combining imidazole with the quasiracemate, racemate, and enantiopure forms of 1 and 2 resulted in crystal structures characterized as molecular salts with layered motifs formed from highly directional N+-H?carboxylate and carboxyl?carboxylate interactions. In contrast to the enantiopure [(+)-1·Im and (-)-2·Im] and racemic [(±)-1·Im and (±)-2·Im] systems, neighboring molecular layers observed in quasiracemate (+)-1/(-)-2·Im are organized by approximate inversion symmetry. Assessment of the crystal packing efficiency for this series of molecular salts via crystal densities and packing coefficients (Ck) indicates imidazole greatly alters the crystal landscape of the system in favor of racemic and quasiracemic crystal packing. A similar desymmetrized crystal environment was also realized for the ternary cocrystalline system of (+)-1/(-)-2·BPDO where the components organize via N+-O-?carboxyl contacts. This study underscores the importance of molecular shape to molecular recognition processes and the stabilizing effect of tailor-made additives for creating new crystalline phases of previously inaccessible crystalline materials.
Preparation of (S)-2-Substituted Succinates by Stereospecific Reductions of Fumarate and Derivatives with Resting Cells of Clostridium formicoaceticum
Eck, Richard,Simon, Helmut
, p. 13631 - 13640 (2007/10/02)
Fumarate derivatives have been reduced to (S)-2-methylsuccinate 2a, (S)-2-ethylsuccinate 3a and (S)-2-chlorosuccinate 4a in up to 1 M concentrations with Clostridium formicoaceticum.Formate was the electron donor and viologens or anthraquinone-2,6-disulphonate acted as artificial electron mediators.Reductions with freeze-dried cells in 2H2O-buffers led to the (2R,3S)--dideuterated succinate derivatives.The productivity numbers ranged from 450 to 5000 and the enantiomeric excess of all (S)-2-substituted succinates was >/= 99percent.
