- Unified Strategy to Amphenicol Antibiotics: Asymmetric Synthesis of (-)-Chloramphenicol, (-)-Azidamphenicol, and (+)-Thiamphenicol and Its (+)-3-Floride
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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.
- Liu, Jinxin,Li, Yaling,Ke, Miaolin,Liu, Minjie,Zhan, Pingping,Xiao, You-Cai,Chen, Fener
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p. 15360 - 15367
(2020/11/30)
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- A substituted 1,2-aminoalcohols method for preparation of drug
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The invention discloses a preparation method of a substituted 1, 2-alkamine medicine. The preparation method comprises the following steps: dissolving a compound A into a solvent, then adding alkali, stirring, dripping a carbonylation agent, and after dripping, stirring, so as to obtain a compound B; dissolving the compound B into the solvent, adding a reducing agent, controlling the temperature of a reaction liquid to range from 10 DEG C below zero to 50 DEG C, and stirring, so as to obtain a compound C; adding the compound C into the solvent, using Ishikawa agent for fluoridation, after fluoridation, obtaining a compound D, removing the solvent, directly adding into acid for hydrolysis so as to obtain a compound E; resolving the compound E, ester and alkali into the solvent for reaction for 2 to 24 hours under a temperature of 0 to 50 DEG C, so as to obtain a compound F; the process route has the characteristics of short production period, low cost and high yield, the operation is simple and convenient, the product yield is increased while unit operation is shortened, and the preparation method is suitable for industrial production.
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Paragraph 0086; 0087
(2016/10/07)
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- A short enantioselective synthesis of (-)-chloramphenicol and (+)-thiamphenicol using tethered aminohydroxylation
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An efficient enantioselective synthesis of (-)-chloramphenicol (1) and (+)-thiamphenicol (2) is described. These antibiotics have been synthesized from commercially available 4-nitrobenzaldehyde and 4-(methylthio)benzaldehyde, respectively, using tethered aminohydroxylation and Sharpless asymmetric epoxidation as the chirality inducing steps.
- George, Shyla,Narina, Srinivasarao V.,Sudalai, Arumugam
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p. 10202 - 10207
(2007/10/03)
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- CYCLOFUNCTIONALISATION REACTIONS OF EPOXYALCOHOL DERIVATIVES. 3. CYCLISATION-ACYL MIGRATION OF N-BENZOYLCARBAMATES TO STEREODEFINED OXAZOLIDINONES. A NEW, DIASTEREOSPECIFIC ROUTE TO THIAMPHENICOL.
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N-Benzoylcarbamates formed in situ from 2,3-epoxyalcohols and PhCONCO undergo clean to C-2 cyclisation followed by N to O acyl migration on treatment with catalytic sodium imidazolide or other bases.Subsequent benzoate cleavage (NaOMe) is accompanied by equilibration of the N-unsubstituted oxazolidinones; cleavage without significant isomerisation is achieved with MeLi or Zn(BH4)2.This methodology is applied in a diastereospecific, 6-step conversion of methyl 4-bromophenyl sulfonate to racemic Thiamphenicol.
- McCombie, S. W.,Nagabhushan, T. L.
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p. 5395 - 5398
(2007/10/02)
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- 2-OXAZOLIDINONES AS REGIOSELECTIVE PROTECTION OF β-AMINO ALCOHOLS IN THE SYNTHESIS OF 2-AMINO-1-ARYL-3-FLUORO-1-PROPANOLS
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The regioselective conversion of threo-2-ethoxycarbonylamino-1--1,3-propanediol, 4, into 4-hydroxymethyl-5--2-oxazolidinone, 8, is described as well as the use of this protection procedure in the synthesis of the fluoro analogue, 2, of thiamphenicol, 1.Methods of hydrolysis of the oxazolidinone ring are revisited for compound 11; new procedures via N-acylated intermediates have been investigated and their application is reported.
- Jommi, Giancarlo,Pagliarin, Roberto,Tavecchia, Paolo,Chiarino, Dario,Fantucci, Mario
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p. 485 - 490
(2007/10/02)
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