138617-82-0Relevant articles and documents
A simple organocatalytic enantioselective synthesis of pregabalin
Bassas, Oriol,Huuskonen, Juhani,Rissanen, Kari,Koskinen, Ari M.P.
experimental part, p. 1340 - 1351 (2009/07/26)
This paper describes a new procedure for the enantioselective synthesis of the important anticonvulsant drug Pregabalin, which shows biological properties as the (S) enantiomer only. The key step of the synthetic sequence is the Michael addition reaction of Meldrum's acid to a nitroalkene mediated by a quinidine derived thiourea. A variety of novel catalysts bearing different groups at the thiourea moiety were synthesized and tested. The most successful catalyst that incorporates a trityl substituent provided up to 75 % ee of (S)- 4. The conjugate addition reaction was carried out on a multigram scale with low loadings of catalyst (10 mol-%). Moreover, the catalyst can be recycled showing the same capability in chemical yield and asymmetric induction. Then, hydrogenation of nitroalkane 4 followed by decarboxylation of diacid 5 provides Pregabalin hydrochloride in 59% overall yield. Enantioenrichment by crystallization of the free amino acid 1 improves the (S)/(R) enantiomeric ratio to 9:1. ? Wiley-VCII Verlag GmbH & Co. KGaA.
Highly enantioselective addition of ketones to nitroolefins catalyzed by new thiourea-amine bifunctional organocatalysts
Tsogoeva, Svetlana B.,Wei, Shengwei
, p. 1451 - 1453 (2008/02/05)
A new and effective organocatalytic system: primary amine derived chiral thiourea catalyst 4a and AcOH-H2O additive, which converts different ketones to γ-nitroketones in high yields (82-99%) and enantioselectivities (90-99%) has been described
(R)-[1-(1-Naphthyl)ethyl] isothiocyanate and (S)-1-phenylethyl isothiocyanate. New chirality recognizing reagents for the determination of enantiomeric purity of chiral amines by NMR
Jeon, Dong Ju,Kim, Jung Soo,Lee, Jung No,Kim, Hyoung Rae,Ryu, Eung K.
, p. 40 - 41 (2007/10/03)
(S)-1-Phenylethyl isothiocyanate and (R)-[1-(1-naphthyl)ethyl] isothiocyanate which are easily formed and stable in aqueous conditions are utilized as new chirality recognizing reagents for the determination of enantiomeric purity of chiral amines by NMR.
