Asymchem Laboratories (tianjin) Co., Ltd.

Asymchem Life Science (tianjin) Co., Ltd

Asymchem Laboratories (fuxin) Co., Ltd.

Jilin Asymchem Pharmaceuticals Co., Ltd.

Jilin Asymchem Laboratories Co., Ltd.

Asymchem Life Science Co., Ltd.

Hao Hong

Jiangping Lu

Na Zhang

Gage James

Enxuan Zhang

Yi Xiao

Xuecheng Jiao

Xichun Feng

Jian Tao

Yan Zhang

Kejian Zhang

Yulei Ma

Fang Liu

Wenyan Yu

Yiming Yang

Ye Liu

Rui Li

Xin Huang

Yibing Cheng

Fuliang Wei

Xin Zhang

Bo Yan

Junjie Yan

Zujian Wang

Guanda Che

Chaoyong Chen

Xingfu Xu

Huiyan Mu

Wei Shen

Feng Zhang

Zhiqing Liu

Sihang Yang

Junqi Zhao

Yu Zhang

Yuxia Cui

Jiadong Zhao

Zhen Zhang

Yanyan Gao

Vyasarayani Williams Rajasekar

Xuewu Dong

Mujiao Zhang

Wanming Shi

Mingjie Feng

Xingfang Sun

Yong Jiang

Mingmin Hao

Yong Luo

Tao Zhang

Gonzalez Miguel

Honglei Yan

Liang Hong

Jinhai Guo

Xian Cheng

Shan Cao

Fan Wang

James Gage

Xiang Wang

The present disclosure provides a device for continuously preparing 2,6-dihydroxybenzaldehyde and use thereof. The device includes a first continuous reaction unit for hydroxy protection reaction, a second continuous reaction unit for lithiation and hydroformylation, and a third continuous reaction unit for deprotection reaction that are connected in series. The third continuous reaction unit includes: a first columnar continuous reactor, connected to the second continuous reaction unit and used for deprotection of the lithiated hydroformylated product while performing liquid separation to obtain an organic phase containing 2,6-dihydroxybenzaldehyde and an aqueous phase.

Device for continuously preparing 2,6-dihydroxybenzaldehyde

The present disclosure provides a preparation method for metformin hydrochloride. The preparation method includes: microwave heating raw materials containing dicyandiamide and dimethylamine hydrochloride, and reacting the two at 100° C. to 160° C. to obtain a product system containing metformin hydrochloride. Microwave heating is adopted to heat the dicyandiamide and the dimethylamine hydrochloride. Compared with a conventional heating mode that requires heat to be gradually transferred from the outside to the inside, microwave heating can directly heat each part inside the reactant, which can make the internal temperature of the reactant more uniform, thereby reducing the generation of impurities.

Preparation method for metformin hydrochloride

An amino acid sequence of the transaminase mutant is an amino acid sequence obtained by a mutation of an amino acid sequence is shown in SEQ ID NO: 1. The mutation occurred at least one of the following mutation sites: G17V, L36P, Q40H, G69Y, H70T, L73A, V77G, V77S, V77T, A78I, Y130M, Y130V, Y130T, N132I, N132T, K141S, K142S, K142T, R143P, G144F, G144W, G144Y, E145D, E145S, E145G, K146R, L148A, L148I and the like.

Transaminase mutant and use thereof

Provided are a transaminase mutant and use thereof. The transaminase mutant has an amino acid sequence obtained by mutation of an amino acid sequence shown in SEQ ID NO:1, the mutation at least includes one of the following mutation site combinations: T7C+S47C, Q78C+A330C, V137C+G313C, A217C+Y252C and L295C+C328C; or the transaminase mutant has an amino acid sequence which has the mutation sites in the mutated amino acid sequence and has 80% or more identity with the mutated amino acid sequence. The transaminase mutant realizes the change of protein structure and functions, reduces the enzyme amount, increases the enantiomeric excess (ee) value of a product, and reduces the difficulty of post-processing, so that the transaminase mutant may be suitable for industrial production.

The disclosure discloses a method for an addition reaction of acetylene and a ketone compound. The method includes the following steps: S1, providing a continuous reaction device, wherein the continuous reaction device includes a plurality of bubble tubular reactors being connected with each other through connecting tubes; feeding a raw material solution containing the ketone compound and alkali into the plurality of bubble tubular reactors, and S3, under normal pressure, pumping acetylene from the bottom of the first bubble tubular reactor for the addition reaction. By applying the technical solution of the invention, acetylene reacts with the ketone compound in the plurality of bubble tubular reactors arranged in series, which can ensure the sufficient gas-liquid contact time, and thus making full use of the acetylene gas, improving the utilization rate thereof, effectively reduing the amount of acetylene, reducing costs, and further improving the safety.

Method for addition reaction of acetylene and ketone compound

A preparation method for a trans-cyclobutane-o-dicarboxylic acid ester and a derivative thereof includes the following steps: in an organic solvent, catalyzing a substrate with a structure as shown in a structural formula I by using organic alkali at 50-90° C. so as to generate isomerization, acquiring the trans-cyclobutane-o-dicarboxylic acid ester or the derivative thereof, herein the structural formula I is as follows: Each R, R, Rand Ris independently one of hydrogen or an alkyl of C-C, and each of Rand Ris independently one of alkyl of C-Cand benzyl.

Preparation method for trans-cyclobutane-o-dicarboxylic acid ester and derivative thereof

The present disclosure discloses a continuous preparation method for a penem intermediate MAP. The continuous preparation method includes the following steps: step S1, in a column-type continuous reactor, using a rhodium-loaded catalyst to catalyze 4-nitrobenzyl(R)-2-diazo-4-((2R,3S)-3-((R)-1-hydroxyethyl)-4-oxoazetidin-2-yl)-3-oxopentanoate to generate a cyclization reaction so as to form a first intermediate, herein the rhodium-loaded catalyst is loaded in the column-type continuous reactor, and the rhodium-loaded catalyst has the following structural formula: step S2, performing an esterification reaction on the first intermediate, a diphenyl chlorophosphate and a diisopropylethylamine in a second continuous reactor, to obtain a product system containing the penem intermediate MAP; and step S3, performing crystallization treatment on the product system, to obtain the penem intermediate MAP.

Continuous preparation method for penem intermediate map

Disclosed are a borohydride reduction stabilizing system and a method for reducing an ester to an alcohol. The borohydride reduction stabilizing system includes: a borohydride reducing agent and a stabilizing agent for stabilizing the borohydride reducing agent. The borohydride reducing agent is sodium borohydride or potassium borohydride. The stabilizing agent is an alkali metal salt of an alcohol. By adding the alkali metal salt of the alcohol, such as sodium alkoxide or potassium alkoxide, on the basis of an existing sodium/potassium borohydride reducing agent, the sodium/potassium borohydride reducing agent may be kept stable without being decomposed under the condition of increased temperature, so that on the one hand, the reducing activity is maintained in a relatively high state, and the condition of excessive use is reduced, and on the other hand, the generation of hydrogen is reduced, and the process risks are reduced.

Borohydride reduction stabilizing system and method for reducing ester to alcohol

Provided are a continuous post-treatment method and device for a penem compound. The method includes the following steps: S1, performing continuous extraction on a reaction crude product of a penem compound, to obtain an extraction heavy phase and an extraction light phase; S2, performing continuous solid-liquid separation on the extraction heavy phase, to obtain a liquid phase separation product; S3, performing continuous pH adjustment on the liquid phase separation product until a pH value thereof is 6.1-6.3, to obtain pH-adjusted solution; and S4, performing continuous crystallization treatment on the pH-adjusted solution by a first crystallization solvent, to obtain a penem compound product. The use of the method has the advantages of high treatment speed and high efficiency, and stable material properties and a low deterioration rate during the treatment, and has better control over the yield and purity of a target product.

Continuous post-treatment method and device for penem compound

Disclosed are a monooxygenase mutant and use thereof. An amino acid sequence of a monooxygenase mutant is an amino acid sequence obtained by mutating an amino acid sequence as shown in SEQ ID NO: 1. Mutation includes at least one of the following mutation sites: site 49, site 60, site 61, site 144, site 145, site 146, site 147, site 167, site 169, site 189, site 246, site 247, site 280, site 284, site 285, site 286, site 287, site 328, site 330, site 332, site 382, site 427, site 428, site 429, site 430, site 431, site 432, site 433, site 434, site 435, site 436, site 438, site 441, site 493, site 494, site 508, site 509, site 510, site 511, site 512, and site 513 sites and the like.

Monooxygenase mutant and use thereof

Provided is a ketoreductase mutant and a method for producing chiral alcohol using the same. The ketoreductase mutant has a sequence with amino acid mutations in the sequence shown in SEQ ID NO:1. The mutation sites include at least one of the following positions: 6th position, 21st position, 42nd position, 58th position, 61st position, 76th position, 87th position, 94th position, 96th position, 108th position, 113th position, 117th position, 144th position, 146th position, 147th position, 149th position, 151st position, 152nd, 156th position, 165th position, 177th position, and 198th position.

Ketoreductase mutant and method for producing chiral alcohols

Provided are a transaminase mutant and a method for producing a chiral amine using the same. An amino acid sequence of the transaminase mutant is an amino acid sequence obtained by mutation occurred in an amino acid sequence as shown in SEQ ID NO: 1, and the mutation includes at least one of the following mutation sites: position 3, position 5, position 8, position 25, position 32, position 45, position 56, position 59, position 60, position 84, position 86, position 164, position 176, position 178, position 180, position 187, position 197, position 206, position 207, position 242, position 245, position 319 and position 324.

Provided is a continuous synthesis method for 1,1'-bicyclic[1.1.1]pentane-1,3-diethyl ketone compounds. The continuous synthesis method comprises: under the irradiation of a light source, continuously conveying raw material A and raw material B to a continuous reaction device for a continuous photochemical reaction to obtain 1,1′-bicyclic[1.1.1]pentane-1,3-diethyl ketone compounds, and controlling the reaction temperature in the continuous reaction device by a temperature control device during the continuous photochemical reaction. A propellane with substituents, as a reaction raw material, is subjected to the above photochemical reaction in the continuous reaction device to reduce the probability of its slow decomposition and deterioration under the irradiation, and greatly improve the conversion rate of the reaction material and product yield.

Continuous synthesis method for 1, 1'-bicyclic [1.1.1]pentane-1,3-diethyl ketone compounds

Disclosed are a modified epoxy resin immobilized enzyme, a preparation method therefor and an application thereof. Herein, the preparation method includes the following steps: modifying an epoxy resin, adding a polyethyleneimine to a modified epoxy resin for further modification, and then adding an enzyme to be immobilized and a glutaraldehyde for immobilization, to obtain the modified epoxy resin immobilized enzyme. The epoxy resin is modified, the polyethyleneimine is added to the modified epoxy resin for the further modification, and an aldehyde group in the resin and an amino group in the polyethyleneimine are covalently bound to each enzyme, then it is activated by the bifunctional reagent glutaraldehyde.

Modified epoxy resin immobilized enzyme, preparation method therefor and application thereof

An amino acid sequence of the monooxygenase mutant is obtained by mutation of an amino acid sequence shown in SEQ ID NO: 1, and the mutation at least includes one of the following mutation sites: 45-th site, 95-th site, 106-th site, 108-th site, 114-th site, 186-th site, 190-th site, 191-th site, 249-th site, 257-th site, 393-th site, 436-th site, 499-th site, 500-th site, 501-th site, 503-th site, 504-th site, 559-th site, and 560-th site.

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Morrisville, NC, United States of America

Hao Hong