56-75-7Relevant academic research and scientific papers
Catalytic Syn-Selective Nitroaldol Approach to Amphenicol Antibiotics: Evolution of a Unified Asymmetric Synthesis of (-)-Chloramphenicol, (-)-Azidamphenicol, (+)-Thiamphenicol, and (+)-Florfenicol
Chen, Fener,Cheng, Dang,Huang, Huashan,Jiang, Meifen,Liu, Minjie,Qu, Hongmin,Xia, Yingqi,Xiong, Tong,Zhang, Yan
, p. 11557 - 11570 (2021/09/02)
A unified strategy for an efficient and high diastereo- and enantioselective synthesis of (-)-chloramphenicol, (-)-azidamphenicol, (+)-thiamphenicol, and (+)-florfenicol based on a key catalytic syn-selective Henry reaction is reported. The stereochemistry of the ligand-enabled copper(II)-catalyzed aryl aldehyde Henry reaction of nitroethanol was first explored to forge a challenging syn-2-amino-1,3-diol structure unit with vicinal stereocenters with excellent stereocontrol. Multistep continuous flow manipulations were carried out to achieve the efficient asymmetric synthesis of this family of amphenicol antibiotics.
Method for continuously preparing chloramphenicol by using micro-reaction system
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Paragraph 0030-0044, (2021/08/19)
The invention belongs to the technical field of pharmaceutical engineering, and particularly relates to a method for continuously preparing chloramphenicol by using a micro-reaction system. The method comprises the following steps: respectively and simultaneously pumping an organic solution of raw materials (1R, 2R)-2-amino-1-(4-aminophenyl) propane-1, 3-diol and an organic solution of methyl dichloroacetate into a micro-reaction system of a first micro-mixer and a first micro-channel reactor which are communicated with each other, and carrying out continuous amidation reaction; adding acetone, water and a buffer solution into the mixed solution flowing out, and then respectively and simultaneously pumping the mixed solution and the aqueous solution of the potassium hydrogen persulfate composite salt into a micro-reaction system of a second micro-mixer and a second micro-channel reactor which are communicated with each other for continuous oxidation reaction; and finally, carrying out quenching, extraction and other processes to obtain a chloramphenicol product. The method is short in reaction time, convenient to operate, continuous, controllable, free of amplification effect and high in technological process efficiency, the yield of the product chloramphenicol is larger than 90%, and the method has good industrial application prospects.
Unified Strategy to Amphenicol Antibiotics: Asymmetric Synthesis of (-)-Chloramphenicol, (-)-Azidamphenicol, and (+)-Thiamphenicol and Its (+)-3-Floride
Liu, Jinxin,Li, Yaling,Ke, Miaolin,Liu, Minjie,Zhan, Pingping,Xiao, You-Cai,Chen, Fener
, p. 15360 - 15367 (2020/11/30)
The asymmetric synthesis of (-)-chloramphenicol, (-)-azidamphenicol, and (+)-thiamphenicol and its (+)-3-floride, (+)-florfenicol, is reported. This approach toward the amphenicol antibiotic family features two key steps: (1) a cinchona alkaloid derived urea-catalyzed aldol reaction allows highly enantioselective access to oxazolidinone gem-diesters and (2) a continuous flow diastereoselective decarboxylation of thermally stable oxazolidinone gem-diesters to form the desired trans-oxazolidinone monoesters with two adjacent stereocenters that provide the desired privileged scaffolds of syn-vicinal amino alcohols in the amphenicol family.
Oxidant controlled regio- and stereodivergent azidohydroxylation of alkenes via I2 catalysis
Prasad,Reddi,Sudalai
, p. 10276 - 10279 (2015/06/25)
A novel, I2 catalyzed regio- and stereodivergent vicinal azidohydroxylation of alkenes leading to 1,2-azidoalcohols in high yields (up to 92%) and excellent dr (up to 98%) has been developed. This unprecedented transformation employs NaN3 and DMF as N- and O-nucleophiles respectively. The role of DMF as the O-source in the reaction has been unequivocally proven by 18O labelling studies.
An unusual peroxo intermediate of the arylamine oxygenase of the chloramphenicol biosynthetic pathway
Makris, Thomas M.,Vu, Van V.,Meier, Katlyn K.,Komor, Anna J.,Rivard, Brent S.,Münck, Eckard,Que, Lawrence,Lipscomb, John D.
supporting information, p. 1608 - 1617 (2015/03/05)
Streptomyces venezuelae CmlI catalyzes the six-electron oxygenation of the arylamine precursor of chloramphenicol in a nonribosomal peptide synthetase (NRPS)-based pathway to yield the nitroaryl group of the antibiotic. Optical, EPR, and M?ssbauer studies show that the enzyme contains a nonheme dinuclear iron cluster. Addition of O2 to the diferrous state of the cluster results in an exceptionally long-lived intermediate (t1/2 = 3 h at 4 °C) that is assigned as a peroxodiferric species (CmlI-peroxo) based upon the observation of an 18O2-sensitive resonance Raman (rR) vibration. CmlI-peroxo is spectroscopically distinct from the well characterized and commonly observed cis-μ-1,2-peroxo (μ-η1:η1) intermediates of nonheme diiron enzymes. Specifically, it exhibits a blue-shifted broad absorption band around 500 nm and a rR spectrum with a β(O-O) that is at least 60 cm-1 lower in energy. M?ssbauer studies of the peroxo state reveal a diferric cluster having iron sites with small quadrupole splittings and distinct isomer shifts (0.54 and 0.62 mm/s). Taken together, the spectroscopic comparisons clearly indicate that CmlI-peroxo does not have a μ- η1:η1-peroxo ligand; we propose that a μ- η1:η2-peroxo ligand accounts for its distinct spectroscopic properties. CmlI-peroxo reacts with a range of arylamine substrates by an apparent second-order process, indicating that CmlI-peroxo is the reactive species of the catalytic cycle. Efficient production of chloramphenicol from the free arylamine precursor suggests that CmlI catalyzes the ultimate step in the biosynthetic pathway and that the precursor is not bound to the NRPS during this step.
Enantioselective synthesis of (-)-chloramphenicol via silver-catalysed asymmetric isocyanoacetate aldol reaction
Franchino, Allegra,Jakubec, Pavol,Dixon, Darren J.
, p. 93 - 96 (2015/12/30)
The highly enantio- and diastereoselective aldol reaction of isocyanoacetates catalysed by Ag2O and cinchona-derived amino phosphines applied to the synthesis of (-)- and (+)-chloramphenicol is described. The concise synthesis showcases the utility of this catalytic asymmetric methodology for the preparation of bioactive compounds possessing α-amino-β-hydroxy motifs.
Stereocontrolled synthesis of syn-β-hydroxy-α-amino acids by direct aldolization of pseudoephenamine glycinamide
Seiple, Ian B.,Mercer, Jaron A. M.,Sussman, Robin J.,Zhang, Ziyang,Myers, Andrew G.
supporting information, p. 4642 - 4647 (2014/05/20)
β-Hydroxy-α-amino acids figure prominently as chiral building blocks in chemical synthesis and serve as precursors to numerous important medicines. Reported herein is a method for the synthesis of β-hydroxy- α-amino acid derivatives by aldolization of pseudoephenamine glycinamide, which can be prepared from pseudoephenamine in a one-flask protocol. Enolization of (R,R)- or (S,S)-pseudoephenamine glycinamide with lithium hexamethyldisilazide in the presence of LiCl followed by addition of an aldehyde or ketone substrate affords aldol addition products that are stereochemically homologous with L- or D-threonine, respectively. These products, which are typically solids, can be obtained in stereoisomerically pure form in yields of 55-98 %, and are readily transformed into β-hydroxy-α-amino acids by mild hydrolysis or into 2-amino-1,3-diols by reduction with sodium borohydride. This new chemistry greatly facilitates the construction of novel antibiotics of several different classes. On aldol: Enolization of (R,R)- or (S,S)-pseudoephenamine glycinamide with lithium hexamethyldisilazide (LiHMDS) in the presence of LiCl followed by addition of either an aldehyde or ketone substrate affords aldol addition products which are stereochemically homologous with L- or D-threonine, respectively. These products can be obtained in stereoisomerically pure form in yields of 55-98 %, and are readily transformed into β-hydroxy-α-amino acids by mild hydrolysis or into 2-amino-1,3-diols by reduction.
Stereoselective synthesis of (-)-chloramphenicol, (+)-thiamphenicol and (+)-sphinganine via chiral tricyclic iminolactone
Li, Qiong,Zhang, Hongbo,Li, Chenguang,Xu, Pengfei
, p. 149 - 153 (2013/08/24)
The stereoselective syntheses of (-)-chloramphenicol, (+)-thiamphenicol and (+)-sphinganine are described. The two continuous chiral centers within three target molecules were constructed through aldol reaction of chiral tricyclic iminolactone and aldehyde. Concise and efficient syntheses of (-)-chloramphenicol, (+)-thiamphenicol and (+)-sphinganine have been accomplished in practical four or three steps. The synthetic route featured in an aldol reaction between iminolactone 1a and 1b with aldehyde, which introduced the two continuous chiral centers within three target molecules. Copyright
Direct synthesis of β-hydroxy-α-amino acids via diastereoselective decarboxylative aldol reaction
Singjunla, Yuttapong,Baudoux, Jeroime,Rouden, Jacques
, p. 5770 - 5773 (2013/12/04)
A straightforward metal-free synthesis of anti-β-hydroxy-α-amino acids is described. The organic base-mediated decarboxylative aldol reaction of cheap, readily available α-amidohemimalonates with various aldehydes afforded under very mild conditions anti-β-hydroxy-α-amido esters in high yields and complete diastereoselectivity. Simple one-pot subsequent transformations enabled the corresponding anti-β-hydroxy-α-amino acids or in a few examples their syn diastereomers to be obtained directly using epimerization conditions.
CmlI is an N-oxygenase in the biosynthesis of chloramphenicol
Lu, Haige,Chanco, Emmanuel,Zhao, Huimin
, p. 7651 - 7654 (2012/09/08)
The N-oxygenation of an amine group is one of the steps in the biosynthesis of the antibiotic chloramphenicol. The non-heme di-iron enzyme CmlI was identified as the enzyme catalyzing this reaction through bioinformatics studies and reconstitution of enzymatic activity. In vitro reconstitution was achieved using phenazine methosulfate and NADH as electron mediators, while in vivo activity was demonstrated in Escherichia coli using two substrates. Kinetic analysis showed a biphasic behavior of the enzyme. Oxidized hydroxylamine and nitroso compounds in the reaction were detected both in vitro and in vivo based on LC-MS. The active site metal was confirmed to be iron based on a ferrozine assay. These findings provide new insights into the biosynthesis of chloramphenicol and could lead to further development of CmlI as a useful biocatalyst.
