51458-28-7Relevant articles and documents
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.
METHODS FOR PREPARING FLORFENIOL AND INTERMEDIATE THEREOF
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, (2021/07/02)
The present invention discloses a method for preparing florfenicol and its intermediate (V), comprising an addition reaction, a ring closure reaction, a hydrolysis reaction, a ring opening reaction, a reduction reaction, a ring reaction, a fluorination reaction and a ring opening reaction. In the present method for preparing florfenicol, respective reaction steps can be continuously operated, therefore the methods of the present invention features simplified process and shorter synthetic route, and obtained florfenicol has high chiral purity and is of high yield. The method of the present invention for preparing florfenicol (TM) using the intermediate (V) avoids waste water pollution and reduces the cost for treating wastewater and alleviates environmental pollution. At the same time, the methods of the present invention eliminates a chiral resolution procedure, thus increasing the utilization rate of atoms in the reaction. As a result, cost is reduced and process is simplified.
One-Pot Asymmetric Synthesis of an Aminodiol Intermediate of Florfenicol Using Engineered Transketolase and Transaminase
Deng, Zixin,Huang, Tingting,Lin, Shuangjun,Liu, Qi,Shi, Ting,Tang, Mancheng,Tao, Wentao,Xie, Xinyue,Zhang, Yuanzhen,Zhao, Yilei
, p. 7477 - 7488 (2021/06/30)
Florfenicol is the 3′-fluoro derivative of thiamphenicol and has been widely used in veterinary medicine for its high antibacterial activity and safety. However, the development of simplified and environmentally friendly catalytic methods for the stereoselective production of florfenicol is a key challenge. Herein, we established a highly stereoselective enzymatic one-pot reaction for the synthesis of an aminodiol intermediate of florfenicol bearing two stereocenters from industrial raw material 4-(methylsulfonyl) benzaldehyde by coupling transketolase (TK) and ω-transaminase (TA). The enantioselectivity of TK from E. coli was converted from (S) (93% ee) to (R) (95% ee), and we also inverted the enantiopreference (E(S) = 9 to E(R) = 12) and ketone/aldehyde substrate selectivity of TA ATA117 via structure-guided enzyme engineering. Docking calculations and molecular dynamics simulations of the wild-type and mutant enzymes unveiled the molecular basis for enzymatic stereocontrol. Using the engineered TK and TA, (1R,2R)-p-methylsulfonyl phenylserinol was biosynthesized with good yield (76%) and high stereoselectivity (96% de and >99% ee). Our work established an enzymatic synthetic route to (1R,2R)-p-methylsulfonyl phenylserinol, facilitating the development of a chemoenzymatic method for producing florfenicol.
Preparation method of florfenicol intermediate
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Paragraph 0021-0045, (2020/10/05)
The invention relates to the technical field of veterinary drugs, in particular to a preparation method of a florfenicol intermediate. The preparation method comprises the following steps: using D-threo-p-methyl sulfonyl phenyl serine as a raw material, adding a solvent, heating, and directly generating amino diol under the actions of a reducing agent and a reduction assistant. The preparation method is simple in process, low in production cost and quick in reaction, and the product yield is greatly improved.
A new key intermediate of preparation method of florfenicol (by machine translation)
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Paragraph 0037-0041; 0045-0049; 0053-0057; 0061-0065, (2019/10/04)
The present invention discloses a new method for the preparation of the key intermediate of the florfenicol, including asymmetric addition reactions and the cyclization reaction, of the present invention simplify the whole line, simple operation, chiral control better, there are broad application prospects. The invention only 2 step reaction, compared with the traditional process of 5 step reaction, is greatly simplified, the operation is simpler, adopts the chiral asymmetric addition reactions, realizes the efficient use of the substrate, compared with the traditional process of less than half of the resolution of the utilization rate of atom, greatly improves the economy of the process, because of the short route, cheap raw materials, and thus greatly reduces the cost of the product, improving the quality of products. (by machine translation)
A florfenicol also the original method for the preparation of (by machine translation)
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Paragraph 0042-0043; 0050-0051; 0058-0059; 0066-0067, (2019/10/23)
The invention discloses a florfenicol also the original of a preparation method of the midbody, is to the chlorobenzene as a starting material, through the asymmetric addition reaction, sodium methyl mercaptan/oxidation reaction to prepare the florfenicol intermediate (1 R, 2 R) - 2 - amino - 1 - (4 - methanesulfonyl) phenyl) propane - 1, 3 - diol, simplify the entire route of the present invention, simple operation, chiral control better, there are broad application prospects. The invention only 2 step reaction, compared with the traditional process of the 4 step reaction, is greatly simplified, the operation is simpler, the efficient use of the substrate, compared to traditional chiral separation process of less than half of the utilization rate of atom, greatly improves the economy of the process. (by machine translation)
Method for purifying (1R,2R)-1-[(4-methylsulfonyl)phenyl]-2-amino-1,3-propanediol
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Paragraph 0047; 0049; 0054; 0056, (2019/10/01)
The invention relates to a method for purifying (1R,2R)-1-[(4-methylsulfonyl)phenyl]-2-amino-1,3-propanediol. A reaction of an amine and a ketone to form a Schiff base, which is a reversible reaction,is used to remove some impurities that are difficult to remove. The method comprises the following steps: crude (1R,2R)-1-[(4-methylsulfonyl)phenyl]-2-amino-1,3-propanediol is mixed with a solvent and a ketone, the obtained mixture is stirred and reacted at 10-80 DEG C, the reacted mixture is cooled to -20-20 DEG C for crystallization, and the obtained mixture is filtered and dried to obtain a Schiff base; and the Schiff base reacts with water at 30-105 DEG C, reaction, the obtained solution is distilled and concentrated, an organic solvent is added, the obtained solution is cooled to -15-25DEG C for crystallization, and the obtained solution is filtered and dried to obtain high-quality (1R,2R)-1-[(4-methylsulfonyl)phenyl]-2-amino-1,3-propanediol with an HPLC purity of above 99.8% andany single impurity content of below 0.1%. The method has the advantages of good purification effect, high product purity, mild reaction conditions, simplicity in operation, and easiness in realization of enlarged production.
Preparation method of florfenicol intermediate (by machine translation)
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Paragraph 0039; 0040, (2019/09/13)
The compound is obtained by carrying out asymmetric addition reaction with nitroethanol under the catalysis of Cu (OTf) and a copper salt complex formed by chiral ligand L, and then carrying out catalytic hydrogenation on palladium carbon . the compound is obtained after catalytic hydrogenation of palladium carbon. 2The route synthesis method is simple to operate, environmentally friendly, and wide in application prospect. (by machine translation)
A (1R, 2R) - 1 - substituted phenyl - 2 - amino - 1, 3 - propanediol
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, (2017/08/24)
The invention belongs to the technical field of pharmaceutical chemistry, and particularly relates to a synthesis method of (1R,2R)-1-substituted-phenyl-2-amino-1,3-propanediol. The preparation method comprises the following steps: rearranging 2-(N-substituted-oxyformacyl-substituted-benzoylamino)acetate to obtain 2-substituted-oxyformamido-3-substituted-phenyl-3-oxopropionate; and carrying out asymmetric transfer hydrogenation with dynamic resolution to obtain (2S,3S)-alpha-substituted-amino-beta-hydroxy ester, and carrying out configuration reversion and deprotection to obtain the (1R,2R)-1-substituted-phenyl-2-amino-1,3-propanediol. The method has the advantages of mild conditions and high optical purity, and is simple to operate and suitable for industrial production.
Catalytic asymmetric transfer hydrogenation/dynamic kinetic resolution: an efficient synthesis of florfenicol
Wang, Xinlong,Xu, Lingjun,Yan, Lingjie,Wang, Haifeng,Han, Sheng,Wu, Yan,Chen, Fener
, p. 1787 - 1793 (2018/03/29)
A robust and practical method has been developed for the synthesis of florfenicol (1) starting from commercial available 4-(methylsulfonyl) benzoic acid. The key step in this synthesis was the Ru-chloramphenicol base catalyzed asymmetric transfer hydrogenation of N-Boc α-amino-β-ketoester 5 through a dynamic kinetic resolution, which afforded the key chiral building block, anti-(2S,3S)-α-Boc-amino-β-hydroxyl ester 4, with high diastereoselectivity (92% de) and enantioselectivity (78% ee). The synthesis of a series of novel chloramphenicol base ligands L1–L10 is also included. This protocol could also be used for the asymmetric synthesis of fully synthetic analogs of florfenicol.
