- Preparation process of optically pure 2-tetrahydrofuroic acid
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The invention discloses a preparation process of optically pure 2-tetrahydrofuroic acid. The preparation process comprises the following steps: carrying out a splitting reaction on L-phenylalaninol with (RS)-2-tetrahydrofuroic acid in a first organic solvent to obtain a diastereoisomer salt, carrying out recrystallization to obtain an (S)-2-tetrahydrofuroic acid crude product, and carrying out post-treatment on the crude product to obtain high-optical purity (S)-2-tetrahydrofuroic acid with an enantiomeric excess (ee) value larger than 99%; and combining the mother liquor with the recrystallization mother liquor to obtain a mixed solution containing (R)-2-tetrahydrofuroic acid, then carrying out a reaction on the (R)-2-tetrahydrofuroic acid in the mixed solution with D-phenylalaninol for saltifying, recrystallizing the obtained salt to obtain an (R)-2-tetrahydrofuroic acid crude product, and carrying out post-treatment on the crude product to obtain high-optical purity (R)-2-tetrahydrofuroic acid with an ee value larger than 99%. According to the invention, the 2-tetrahydrofuroic acid is effectively split by using the two configurations of optically pure phenylalaninol, and the twooptical isomers of the 2-tetrahydrofuroic acid are separately obtained, and the ee values of the two optical isomers are both larger than 99%; secondly, the solvents, such as acetone, ethyl acetate and the like which are low in price and low in boiling point are used as solvents for the splitting reaction and recrystallization, the solvents are easy to recycle, and the recovery rate is high.
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Paragraph 0026; 0030; 0031
(2019/05/15)
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- Chiral ammonium hypoiodite salt-catalyzed enantioselective oxidative cycloetherification to 2-acyl tetrahydrofurans
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2-Acyl tetrahydrofuran is a fundamental structure in natural products and pharmaceuticals. We achieved chiral quaternary ammonium hypoiodite salt-catalyzed enantioselective oxidative cycloetherification of δ-hydroxyketone derivatives. The corresponding 2-acyl tetrahydrofurans were obtained in high chemical yield with high enantioselectivity.
- Uyanik, Muhammet,Hayashi, Hiroki,Iwata, Hirokazu,Ishihara, Kazuaki
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p. 353 - 355
(2016/05/09)
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- Highly diastereoselective hydrogenation of furan-2-carboxylic acid derivatives on heterogeneous catalysts
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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
- Sebek, Michael,Holz, Jens,B?rner, Armin,J?hnisch, Klaus
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experimental part
p. 461 - 465
(2009/08/09)
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- A scalable chemoenzymatic preparation of (R)-tetrahydrofuran-2-carboxylic acid
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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.
- Fujima, Yoshito,Hirayama, Yoshihiro,Ikunaka, Masaya,Nishimoto, Yukifumi
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p. 1385 - 1391
(2007/10/03)
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- Synthesis, Structure, and Pharmacological Evaluation of the Stereoisomers of Furnidipine
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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.
- Alajarin, Ramon,Vaguero, Juan J.,Alvarez-Builla, Julio,Pastor, Manuel,Sunkel, Carlos,et al.
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p. 2830 - 2841
(2007/10/02)
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- Synthesis and Chromatographic Separation of the Stereoisomers of Furnidipine
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The four stereoisomers of methyl tetrahydrofuran-2-ylmethyl 2,6-dimethyl-4-(o-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (furnidipine), have been synthesized and separated by chiral chromatography using D-phenylglycine as chiral stationary phase.Enantiomeric purity of stereoisomers is determined by HPLC-CSP technique and configurations deduced via X-ray crystallography.
- Alajarin, Ramon,Alvarez-Builla, Julio,Vaguero, Juan J.,Sunkel, Carlos,Casa-Juana, Miguel Fau de,et al.
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p. 617 - 620
(2007/10/02)
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- Process for preparing optically active tetrahydro-2-furoic acid
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A process for preparing an optically active tetrahydro-2-furoic acid is disclosed. The process comprises (i) reacting (±)-tetrahydro-2-furoic acid with an optically active amine resolver of the following formula (I): STR1 wherein R1 is a lower alkyl group and R2 represents an alkyl group or ar aryl group, provided that R1 and R2 are different from each other, thus producing an optically active diastereomer salt, and (ii) decomposing the diastereomer salt. According to the process, a high purity, optically active tetrahydro-2-furoic acid can be prepared at a high yield using an amine resolver. The amine resolver can be recovered at a high yield and high purity.
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- Syntheses of optically active 2-tetrahydrofuran derivatives
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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.
- Belanger, Patrice C.,Williams, Haydn W. R.
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p. 1383 - 1386
(2007/10/02)
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