87324-00-3Relevant academic research and scientific papers
Anti-Selective Catalytic Asymmetric Nitroaldol Reaction of α-Keto Esters: Intriguing Solvent Effect, Flow Reaction, and Synthesis of Active Pharmaceutical Ingredients
Karasawa, Tomoya,Oriez, Rapha?l,Kumagai, Naoya,Shibasaki, Masakatsu
supporting information, p. 12290 - 12295 (2018/09/27)
A rare-earth metal/alkali metal bimetallic catalyst proved particularly effective for enantioselectively coupling nitroalkanes and α-keto esters in an anti-selective manner to afford synthetically versatile, densely functionalized, and optically active α-nitro tertiary alcohols. A chiral diamide ligand captured two distinct metal cations, giving rise to a catalytically competent solid-phase heterobimetallic catalyst by simple mixing via self-assembly. The advantage of the solid-phase asymmetric catalyst was realized by successful application to the enantio- and diastereoselective reaction in a continuous-flow platform. The use of closely related solvents in terms of structures and polarity parameters, THF and its methylated congener 2-Me-THF, had an unexpectedly large solvent effect both on the reaction rate and the stereoselectivity. The nitroaldol products share a privileged unit for active pharmaceutical ingredients, as demonstrated by the streamlined enantioselective synthesis of the marketed antifungal agents efinaconazole and albaconazole.
Nucleotide competing reverse transcriptase inhibitors: Discovery of a series of non-basic benzofurano[3,2-d]pyrimidin-2-one derived inhibitors
James, Clint A.,Deroy, Patrick,Duplessis, Martin,Edwards, Paul J.,Halmos, Teddy,Minville, Joannie,Morency, Louis,Morin, Sébastien,Simoneau, Bruno,Tremblay, Martin,Bethell, Richard,Cordingley, Michael,Duan, Jianmin,Lamorte, Louie,Pelletier, Alex,Rajotte, Daniel,Salois, Patrick,Tremblay, Sonia,Sturino, Claudio F.
, p. 2781 - 2786 (2013/06/27)
A HTS screen led to the identification of a benzofurano[3,2-d]pyrimidin-2- one core structure which upon further optimization resulted in 1 as a potent HIV-1 nucleotide competing reverse transcriptase inhibitor (NcRTI). Investigation of the SAR at N-1 allowed significant improvements in potency and when combined with the incorporation of heterocycles at C-8 resulted in potent analogues not requiring a basic amine to achieve antiviral activity. Additional modifications at N-1 resulted in 33 which demonstrated excellent antiviral potency and improved physicochemical properties.
QUINOLINE DERIVATIVE
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Page/Page column 37, (2011/12/14)
The present invention provides a compound having a melanin-concentrating hormone receptor antagonistic action and low toxicity, which is useful as an agent for the prophylaxis or treatment of obesity and the like. The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.
Highly diastereoselective hydrogenation of furan-2-carboxylic acid derivatives on heterogeneous catalysts
Sebek, Michael,Holz, Jens,B?rner, Armin,J?hnisch, Klaus
experimental part, p. 461 - 465 (2009/08/09)
The heterogeneously catalyzed diastereoselective hydrogenation of furan-2-carboxylic acid derivatives modified with chiral auxiliaries is described. Chiral auxiliaries, catalysts, solvents, and additives were optimized for the reaction. Finally, the hydro
Asymmetric hydrolysis of 2-hydroxy-carboxylic esters using recombinant Escherichia coli
Nakagawa, Atsushi,Kato, Ko,Shinmyo, Atsuhiko,Suzuki, Toshio
, p. 2394 - 2398 (2008/03/13)
Optically active 2-hydroxy-carboxylates are important compounds for their use as intermediates in the synthesis of pharmaceuticals and stereoblock polymers. Enterobacter sp. DS-S-75 and the recombinant Escherichia coli harbouring the 4-chloro-3-hydroxybutyrate (CHB) hydrolase gene from the strain DS-S-75 showed asymmetric hydrolytic activity towards 2-hydroxy-carboxylates, as well as towards CHB. It was discussed that the hydroxyl group in the substrate was particularly important for the asymmetric hydrolytic activity of the CHB hydrolase, and as such, it was re-designated to EnHCH (hydroxy-carboxylic ester hydrolase derived from Enterobacter sp.). Using the recombinant cell, both the reaction rate and the concentration of the substrates were significantly improved upon when compared to that of DS-S-75. Optically active 2-hydroxy-carboxylates could be synthesized on a practical basis for industrial production in this report.
A scalable chemoenzymatic preparation of (R)-tetrahydrofuran-2-carboxylic acid
Fujima, Yoshito,Hirayama, Yoshihiro,Ikunaka, Masaya,Nishimoto, Yukifumi
, p. 1385 - 1391 (2007/10/03)
To develop a practical scalable approach to (R)-tetrahydrofuran-2-carboxylic acid (THFC) 1, a chiral building block for furopenem 2, enantioselective hydrolysis of its esters is explored: When ethyl (±)-tetrahydrofuran-2-carboxylate 3d (2 M, 288 g/L) is digested by an Aspergillus melleus protease {0.2% (w/v)} in a 1.5 M potassium phosphate buffer (pH 8) for 20 h, enantioselective hydrolysis proceeds with E=60 to give (R)-THFC 1 in 94.4% ee. On separation from the left-over antipodal ester (S)-3d by partition, (R)-THFC 1 is treated with N,N-dicyclohexylamine (DCHA) in methyl ethyl ketone/methanol (5:1) to precipitate the crystalline salt 4 that contains (R)-THFC 1 of >99% ee in 22% overall yield from (±)-3d.
Synthesis, Structure, and Pharmacological Evaluation of the Stereoisomers of Furnidipine
Alajarin, Ramon,Vaguero, Juan J.,Alvarez-Builla, Julio,Pastor, Manuel,Sunkel, Carlos,et al.
, p. 2830 - 2841 (2007/10/02)
The synthesis and pharmacological activities of the four stereoisomers of methyl tetrahydrofuran-2-ylmethyl 2,6-dimethyl-4-(2'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (furnidipine) are reported.The four isomers were synthesized by a modified Hantzsch synthesis by reaction of (-)- or (+)-tetrahydrofuran-2-ylmethyl 3-aminocrotonate and methyl 2-acetoacetate or, alternatively, by reaction of (-)- or (+)-tetrahydrofuran-2-ylmethyl 2-acetoacetate and methyl 3-aminocrotonate.The 1:1 diasteromeric mixture thus obtained were separated by chromatography, using poly(D-phenylglycine) as the chiral stationary phase.The enantiomeric purity of the stereoisomers was determined by high-performance liquid chromatography-chiral stationary phase technique (HPLC-CSP).Attempts to obtain crystals of a single stereoisomer failed in different solvent, while methanol crystallization of the product obtained from (+/-)-tetrahydrofuran-2-ylmethyl 2-acetoacetate and methyl 3-aminocrotonate yielded good-quality crystals of the most insoluble racemate which proved to be a mixture of the (SS)/(RR) enantiomers by X-ray crystaloography.Conformational analysis of the stereoisomers, assuming rotation of the aryl substituent and ester groups, shows small energy differences (about 4 kcal*mol-1) between the most and the least favorable conformations.Binding studies were performed using isradipine as a reference ligand.The results showed stereospecificity of the furnidipine isomers in brain, ileum, and cardiac tissues, the (SS) and (SR)-isomers clearly being more potent than their (RR)- and (RS)-enantiomers.The (SS)- and (SR)-isomers were also more selective on cerebral tissue when compared with ileal and cardiac preparations.
Syntheses of optically active 2-tetrahydrofuran derivatives
Belanger, Patrice C.,Williams, Haydn W. R.
, p. 1383 - 1386 (2007/10/02)
The resolution of 2-tetrahydrofuran-carboxylic acid and assignment of configuration to the enantiomers are reported.New syntheses of the enantiomers of 2-tetrahydofurancarboxaldehyde are also described.
