138617-82-0Relevant academic research and scientific papers
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.
Crystallographic, 1H NMR and CD studies of sterically strained thiourea anion receptors possessing two stereogenic centres
Ali, Haslin Dato Paduka,Quinn, Susan J.,McCabe, Thomas,Kruger, Paul E.,Gunnlaugsson, Thorfinnur
experimental part, p. 793 - 800 (2009/06/19)
The synthesis and structural characterisation of three chiral bis-naphthalene thiourea receptors (1-3) derived from (R)-(+)-1-(1-naphthyl) ethylamine and (S)-(-)-1-(1-naphthyl)ethylamine are reported along with spectroscopic studies to screen their potential as anion receptors/sensors. Their solid state structures were analysed by X-ray crystallography and their ability to bind anions such as acetate and phosphate in DMSO solution investigated by 1H NMR, absorption, fluorescence and circular dichroism spectroscopy.
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
Modified guanidines as potential chiral superbases. 2. Preparation of 1,3-unsubstituted and 1-substituted 2-iminoimidazolidine derivatives and a related guanidine by the 2-chloro-1,3-dimethylimidazolinium chloride-induced cyclization of thioureas
Isobe,Fukuda,Tokunaga,Seki,Yamaguchi,Ishikawa
, p. 7774 - 7778 (2007/10/03)
Simple preparation methods for modified guanidines were explored for new chiral superbases. Thus, (4S,5S)-4,5-diphenyl- and diastereomeric cyclohexane-fused 2-iminoimidazolidines were prepared from (1S,2S) - 1,2 -diphenylethylenediamine and (1R,2R)- or (1S,2S)-1,2-diaminocyclohexanes through cyclization of protected thiourea intermediates with 2-chloro-1,3-dimethylimidazolinium chloride (DMC) as a key reaction. In the (4S,5S)-4,5-diphenyl series 1-methyl-2-iminoimidazolidines and 2-diethylaminoimidazoline were also prepared as related guanidines.
(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.
