22146-57-2Relevant academic research and scientific papers
Asymmetric hydrogenation reaction of alpha-ketoacids compound
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Paragraph 0037; 0044, (2016/10/10)
The invention relates to the technical field of organic chemistry, especially to an asymmetric hydrogenation reaction of an alpha-ketoacids compound. The asymmetric hydrogenation reaction comprises a scheme shown in the description. In the scheme, R1 is phenyl, substituted phenyl, naphthyl, substituted naphthyl, C1-C6 alkyl, or aralkyl; a substituent group is C1-C6 alkyl, C1-C6 alkoxy, or halogen; and the number of the substituent group is 1-3. In the scheme, M is a chiral spiro-pyridylamino phosphine ligand iridium complex having a structure shown in the description. In the structure, R is hydrogen, 3-methyl, 4-tBu, or 6-methyl.
Direct asymmetric hydrogenation of α-keto acids by using the highly efficient chiral spiro iridium catalysts
Yan, Pu-Cha,Xie, Jian-Hua,Zhang, Xiang-Dong,Chen, Kang,Li, Yuan-Qiang,Zhou, Qi-Lin,Che, Da-Qing
supporting information, p. 15987 - 15990 (2015/02/19)
A new efficient and highly enantioselective direct asymmetric hydrogenation of α-keto acids employing the Ir/SpiroPAP catalyst under mild reaction conditions has been developed. This method might be feasible for the preparation of a series of chiral α-hydroxy acids on a large scale.
Reaction intermediate analogues as bisubstrate inhibitors of pantothenate synthetase
Xu, Zhixiang,Yin, Wei,Martinelli, Leonardo K.,Evans, Joanna,Chen, Jinglei,Yu, Yang,Wilson, Daniel J.,Mizrahi, Valerie,Qiao, Chunhua,Aldrich, Courtney C.
, p. 1726 - 1735 (2014/03/21)
The biosynthesis of pantothenate, the core of coenzyme A (CoA), has been considered an attractive target for the development of antimicrobial agents since this pathway is essential in prokaryotes, but absent in mammals. Pantothenate synthetase, encoded by the gene panC, catalyzes the final condensation of pantoic acid with β-alanine to afford pantothenate via an intermediate pantoyl adenylate. We describe the synthesis and biochemical characterization of five PanC inhibitors that mimic the intermediate pantoyl adenylate. These inhibitors are competitive inhibitors with respect to pantoic acid and possess submicromolar to micromolar inhibition constants. The observed SAR is rationalized through molecular docking studies based on the reported co-crystal structure of 1a with PanC. Finally, whole cell activity is assessed against wild-type Mtb as well as a PanC knockdown strain where PanC is depleted to less than 5% of wild-type levels.
Stereoselective synthesis of a potent thrombin inhibitor by a novel P2-P3 lactone ring opening
Nelson, Todd D.,LeBlond, Carl R.,Frantz, Doug E.,Matty, Louis,Mitten, Jeffrey V.,Weaver, Damian G.,Moore, Jeffrey C.,Kim, Jaehon M.,Boyd, Russell,Kim, Pei-Yi,Gbewonyo, Kodzo,Brower, Mark,Sturr, Michael,McLaughlin, Kathleen,McMasters, Daniel R.,Kress, Michael H.,McNamara, James M.,Dolling, Ulf H.
, p. 3620 - 3627 (2007/10/03)
The concise synthesis of a potent thrombin inhibitor was accomplished by a mild lactone aminolysis between an orthogonally protected bis-benzylic amine and a diastereomerically pure lactone. The lactone was synthesized by the condensation of L-proline met
N-heterocyclic bicyclic lactone compounds
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Page 7, (2010/02/06)
Novel N-heterocyclic bicyclic lactone compounds of formula I and its novel hydroxyamide precursors of formula IV, are synthesized by coupling a hydroxy acid of formula II with an ester of formula III or a pharmaceutically acceptable salt thereof, in the presence of a peptide coupling reagent to produce a hydroxyamide of formula IV, and cyclizing the hydroxyamide of formula IV to produce compounds of formula 1.
Thrombin inhibitors
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, (2008/06/13)
Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, e.g. 1-(3(S)-Cyclopropyl-2(R)-hydroxybutanoyl)azetidine-2(S)-N-(2-aminomethyl-5-chlorobenzyl)carboxamide, and 1-(3-Cyclopropyl-3-methyl-2(R)-hydroxybutanoyl)azetidine-2(S)-N-(2-aminomethyl-5-chlorobenzyl)carboxamide.
Thrombin inhibitors
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, (2008/06/13)
Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, e.g. 1-(3(S)-Cyclopropyl-2(R)-hydroxybutanoyl)azetidine-2(S)-N-(2-aminomethyl-5-chlorobenzyl)carboxamide, and 1-(3-Cyclopropyl-3-methyl-2(R)-hydroxybutanoyl)azetidine-2(S)-N-(2-aminomethyl-5-chlorobenzyl)carboxamide.
Thrombin inhibitors
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, (2008/06/13)
Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, e.g. where R3 is —CH2NH2, —CH2CH2NH2, or —CH2NHC(O)OC(CH3)3.
Enantioseparation of racemic organic ammonium perchlorates by a silica gel bound optically active di-tert-butylpyridino-18-crown-6 ligand
Koentoes, Zoltan,Huszthy, Peter,Bradshaw, Jerald S.,Izatt, Reed M.
, p. 2087 - 2100 (2007/10/03)
Both enantiomers of the novel chiral di-tert-butylpyridino-18-crown-6 ligand (R,R)-7 and (S,S)-7 containing an allyloxy group on the pyridine subcyclic unit were prepared by the reaction of 4-allyloxy-2,6-pyridinedimethyl ditosylate 9 and the enantiomers of di-tert-butyl-substituted tetraethylene glycol (R,R)-8 and (S,S)-8 in the presence of a strong base. One of them, (R,R)-7, was covalently attached to silica gel, and this chiral stationary phase (CSP) separated four selected racemic organic ammonium perchlorates into their enantiomers by column chromatography.
Synthesis of a Chiral, Nonracemic Aziridinone (α-Lactam)
Quast, Helmut,Leybach, Holger
, p. 849 - 859 (2007/10/02)
(S)-tert-Leucine is diazotized affording a mixture of the expected α-chloro and α-hydroxy acids (S)-15 and (S)-16 and the rearranged β-chloro and β-hydroxy acids (R)-12 and (S)-11.Separation produces a 51percent yield of pure (S)-15 (e.e. >= 97.4percent) which is converted via the acid chloride (S)-17 into the α-chloro amides (S)-18a and b (e.e. = 99.0 and 95.2percent, respectively).On treatment with tBuOK, the latter is converted into the α-lactam (R)-22b (59percent, e.e. >= 91.0percent, D20 = -293.7), which is accompanied by small amounts of its ring opening product (R)-23b.Only the α-amino ester (R)-23a is formed from the α-chloro amide (S)-18a and tBuOK.While the enantiomers of the halo amides 13, 18a, b, 24a, b and of the 3-pentyl esters of the hydroxy acid 16 are separated by GC on chiral columns, the α-lactam 22b and the α-amino esters 23a, b require conversion into separable derivatives without involving the stereogenic center.Thus, alkaline hydrolysis of 22b as well as acidic cleavage of 23 yield the α-amino acids 25 which are cyclized to the oxazolidine-2,5-diones 26 by means of bis(trichloromethyl)carbonate ("triphosgene").As shown by the high enantiomeric excess of the products derived from (S)-tert-leucine none of the reactions described results in a considerable degree of racemization.Authentic samples of 11 and 12 are synthesized from the Reformatzky product 21.The absolute configurations of the major enantiomers derived from (S)-14 are based on the retention on chiral GC columns, the signs of optical rotations, and CD spectra.The mechanism of the rearrangement leading to the β-hydroxy and β-chloro acids (S)-11 and (R)-12 is interpreted in terms of a stereospecific 1,2-methyl shift occurring simultaneously with the ring cleavage of the (protonated) α-lactone (R)-2 (R = tBu) which is the crucial intermediate formed in the diazotization of (S)-14.
