Method for preparing chiral (2S,3R)-p-methyl sulfone phenyl ethyl serinate

A technology of thiamphenyl phenylserine ethyl ester and p-methylsulfone group, which is applied in the field of preparation of chiral-p-thiamphenyl phenylserine ethyl ester, which can solve the problems of large environmental hazards, cumbersome resolution steps, poor stereoselectivity, etc. problems, to achieve the effect of cost reduction, simple operation and mild conditions

Active Publication Date: 2019-06-04
SUZHOU LEAD BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] 1. This route requires chiral resolution, and the theoretical yield of the resolution is only 50%, which leads to the yield of the whole route being below 35%. In addition, the steps of resolution are very cumbersome, which brings a great deal of burden to industrial production. the inconvenience
[0009] 2. A large amount of copper salt needs to be used in the condensation process of this route, and the whole process produces a large amount of waste water with metal copper ions; in addition, the splitting process of the racemate also produces a large amount of waste water and solid waste. This method is harmful to the environment. very dangerous
[0010] 3. In this route, in order to remove the residual copper ions in the product, it is necessary to use foul-smelling hydrogen sulfide gas, and the treatment of waste gas is also a major difficulty in this process
[0015] At present, this method still has defects such as low conversion rate, large amount of glycine, poor stereoselectivity, and difficult separation and purification of products, and it does not yet have the conditions for industrialization.

Method used

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  • Method for preparing chiral (2S,3R)-p-methyl sulfone phenyl ethyl serinate
  • Method for preparing chiral (2S,3R)-p-methyl sulfone phenyl ethyl serinate
  • Method for preparing chiral (2S,3R)-p-methyl sulfone phenyl ethyl serinate

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Experimental program
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Effect test

Embodiment 1

[0031] In a 250mL reaction flask, add 2g p-thymphenylbenzaldehyde, 1.55gL-threonine, 0.1g magnesium chloride, 4mg pyridoxal phosphate, 100mL100mM phosphate buffer solution (pH7.0) and heat to 30°C with magnetic stirring until uniform, add 10mg transaldolase enzyme powder (purchased from Suzhou Pivot Biotechnology Co., Ltd., product number is YH1058, here only provides one of the products of the type to illustrate the effect of the present invention), start stirring reaction, and sample HPLC detection after 20 hours The conversion rate is above 95%. After the reaction was completed, the temperature in the reaction system was slowly raised to 70-80° C. and stirred for 0.5 hours, filtered (diatomaceous earth filter), and the filtrate was concentrated to 10 ml. The resulting aqueous solution was adjusted to pH 11 with 40% NaOH, and 0.6 equivalent of CaCl was added 2 , stirred at room temperature for 2-3 hours, at which time a large amount of white solid precipitated. The tempera...

Embodiment 2

[0033] Take 2 g of the above white solid crude product, add 20 ml of ethanol, and cool the system down to 0°C. Slowly add 1.2 equivalents of sulfuric acid to the reaction system dropwise. After the dropwise addition, the temperature of the system was raised to reflux, and the temperature was lowered to room temperature after reflux for 8 hours. Filter to remove calcium sulfate. The filtrate was concentrated to 5ml and neutralized with aqueous ammonia to pH=8.5. The system was cooled to 0°C and stirred for 1 hour, and a large amount of white solid precipitated out. Filtered, washed with a small amount of ice water, sucked dry, and dried under vacuum at 60°C to obtain 1.71 g of (2S,3R)-p-methylsulfonylphenylserine ethyl ester with a yield of 83%.

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Abstract

The invention provides a method for preparing (2S, 3R)-p-methyl sulfone phenyl ethyl serinate from the cheap and easily available methylsulfonyl benzaldehyde and L-threonine under the action of transaldolase. The amino acid intermediate then undergoes ethyl esterification to obtain a target product (2S, 3R)-p-methyl sulfone phenyl ethyl serinate.

Description

technical field [0001] The invention belongs to the technical fields of biological pharmacy and biochemical industry, and in particular relates to a preparation method of chiral (2S, 3R)-p-thymphenylphenylserine ethyl ester. Background technique [0002] Florfenicol is a broad-spectrum antibacterial drug, mainly used for bacterial diseases of cattle, pigs, chickens, ducks, fish and other animals. Thiamphenicol is a drug mainly used for human treatment of respiratory, urinary, hepatobiliary, typhoid and other intestinal surgery, obstetrics and gynecology and ENT infections, especially for moderate and mild infections. (2S,3R)-P-thymphenylphenylserine ethyl ester is a key intermediate in the synthesis of these drugs. Therefore, exploring a mild, efficient and economical method to prepare (2S,3R)-p-thymphenylphenylserine ethyl ester has attracted the attention of chemical and biological workers. [0003] (2S,3R)-P-thymphenylphenylserine ethyl ester, its structural formula is ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C315/04C07C317/48C12P13/04
Inventor 谢新开徐伟黄晓飞
Owner SUZHOU LEAD BIOTECH CO LTD
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