38 results about "Phenylglycine methyl ester" patented technology

The invention provides cefaclor and a synthetic method thereof. The synthetic method of cefaclor comprises that in the presence of an enzyme, cefaclor is generated by forming a reaction mixed solution of 7-ACCA and a D-phenylglycine methyl ester salt derivative and performing reaction, wherein cefaclor crystal seeds are added into the reaction mixed solution, and the crystal seeds are added before cefaclor generated in the reaction is precipitated. The method helps to improve the reaction efficiency, shorten the synthetic period, improve the conversion rate of 7-ACCA and improve the purity of obtained cefaclor.

The invention relates to division of a clopidogrel intermediate 2-substituted phenylglycine methyl ester (or acid), which is a medicine for resisting platelet aggregation. The 2-substituted phenylglycine methyl ester (or acid) has the structure shown in a structural formula I. By utilizing the method, the raw materials and the reagents are low-priced and easily obtained, the reaction conditions are mild and the yield is satisfactory, reaching 98 percent. Therefore, the method for dividing the 2-substituted phenylglycine methyl ester (or acid) is easily industrialized. In the structural formula I, R is equal to H, alkyl (C1-C4, benzene)X is equal to a halogen, and for OR1 and SR1, R1 is equal to H or alkane(C1-C3) is equal to a benzene or the benzene for free substitution.

The present invention discloses isolation of Penicillin Acylase (PA) from Achromobacter sp CCM 4824 expressed in recombinant strain E. coli BL21 CCM 7394 bearing the recombinant plasmid pKXIP1 and processing of PA into biocatalyst useful for the industrial synthesis of antibiotics. More particularly the invention discloses a synthesis of semi-synthetic [beta]-lactam antibiotics in the reaction mixture consisting of activated acyl-donor (D-p-hydroxyphenylglycine methyl ester or amide for Amoxicillin and Cefadroxil; D-phenylglycine methyl ester or amide for Ampicillin and Cephalexin) and nucleophile (6-APA or 7-ADCA) catalyzed by PA obtained from recombinant E. coli BL21 CCM 7394 as the biocatalyst.

The invention discloses a method for analyzing 2-chlorophenylglycine methyl ester tartrate and impurities. The main impurities are phenylglycine methyl ester and m-chlorophenylglycine methyl ester. A high performance liquid chromatography method is adopted, an acid aqueous solution and an organic solvent are used as mobile phases, gradient elution is carried out on a sample solution of the chlorophenylglycine methyl ester, and the method is rapid, simple, accurate, good in repeatability and suitable for control and impurity research of the chlorophenylglycine methyl ester tartrate and impurities.

The present invention relates to a kind of synthesis method of amoxicillin production intermediate, use DL-p-hydroxyphenylglycine and methanol as raw materials, and use solid phosphoric acid as catalyst to synthesize D-p-hydroxyphenylglycine methyl ester, including preparation of solid phosphoric acid catalyst, DL-p-hydroxyphenylglycine Preparation of p-hydroxyphenylglycine methyl ester, hydrolysis of solid phosphoric acid catalyst, crystallization of D-p-hydroxyphenylglycine methyl ester and racemization of crystallization mother liquor in 5 parts. In the present invention, the solid phosphoric acid catalyst can be hydrolyzed into phosphoric acid after the esterification is completed, and forms a phosphoric acid double salt with DL-p-hydroxyphenylglycine methyl ester. ‑Resolving agent for methyl p-hydroxyphenylglycine. In the present invention, the synthesis and resolution of DL-p-hydroxyphenylglycine methyl ester is carried out in methanol aqueous solution, and the crystallization mother liquor is recycled, which greatly reduces the generation of waste liquid, and is a clean production process of D-p-hydroxyphenylglycine methyl ester.

The invention discloses a method for preparing cephradine. Under the catalysis of enzymes, 7-ADCA and dihydrophenylglycine methyl ester are reacted in an enzyme-catalyzed reactor equipped with a two-phase system to form cephradine. The lower phase is separated and filtered to remove cephradine, and the mother liquor is returned to the enzyme-catalyzed reactor for circular reaction. The present invention adopts enzymatic method to synthesize cephradine, less solvent is used, the pollution to the environment is reduced, the two-phase system is adopted, the products inhibiting the reaction and some by-products can be separated in time during the reaction process, and the synthesis reaction and the product can be realized The separation cycle is carried out, thereby greatly improving the conversion rate of the reaction.

The invention discloses a penicillin G acylation enzyme mutant, and application thereof in synthesis of cephalosporin antibiotics. An amino acid sequence of the penicillin G acylation enzyme mutant is shown in SEQ ID NO.1; a nucleotide sequence of an encoding gene is shown in SEQ ID NO.2. The invention also provides application of the penicillin G acylation enzyme mutant in synthesis of cefaclor. The invention provides a novel penicillin acylation enzyme mutant. Compared with the wild penicillin acylation enzyme mutant, the penicillin G acylation enzyme mutant has higher activity in synthesis of cephalosporin antibiotics, such as cefprozil, cefaclor or cefadroxil; especially when the penicillin G acylation enzyme mutant is used for catalyzing 7-ACCA and phenylglycine methyl ester to synthesize the cefaclor, the vitality is improved to 29.8U / mg from 1.2U / mg in the past, the synthesis and hydrolysis activity is almost consistent with that of the wild penicillin acylation enzyme mutant, the synthesis and hydrolysis ratio can be up to 1.7, and the yield of the cefaclor can be up to 71.5%.

The invention provides a method for enzymatically synthesizing cefaclor, comprising the following steps: adding 7-amino-3-chloro-cephemic acid to a mixed solvent, adjusting the pH to 8.1-8.3, and adding immobilized cefaclor synthase , adding D-p-phenylglycine methyl ester hydrochloride and D-phenylglycine methyl ester to carry out the enzyme-catalyzed synthesis reaction. After the reaction, the reaction solution and immobilized cefaclor synthetase were separated to obtain cefaclor crude product and recrystallized , to obtain the cefaclor product; wherein, the mixed solvent includes methanol, glutaraldehyde and soluble phosphate. The preparation method provided by the invention does not need to control the pH value of the reaction process, and significantly improves the number of recycling enzymes recovered in the reaction, and the purity of the prepared cefaclor product can reach more than 99%, and the bulk density can reach 6.2g More than / mL, the recycled enzyme can be used up to 200 times, which simplifies the production process, reduces the production cost, and is suitable for large-scale industrial production.

The invention discloses reaction equipment for synthesizing D-phenylglycine methyl ester hydrochloride, belongs to the technical field of reaction equipment for synthesizing the D-phenylglycine methyl ester hydrochloride, and solves the problems that reaction substances in a reaction kettle are especially hard to sample, for example, equipment is excessively large, the reaction substances are located at the bottom of the equipment during primary reaction, and accordingly the reaction substances are hard to sample, and the like in the prior art. The reaction equipment comprises a kettle, wherein the kettle is provided with lugs, an observation port, a feeding port, a discharge port and heating pipes, a stirring device is arranged in the kettle, a plurality of sampling pipes are arranged on the outer wall of the kettle, the sampling pipes incline 15-45 degrees outwardly, and the sampling outlet of each sampling pipe is higher than the connection part of the previous sampling pipe and the kettle.

The invention provides a preparation method of D-phenylglycine methyl ester hydrochloride / D-dihydrophenylglycine methyl ester hydrochloride, comprising the following steps: (a) mixing D-phenylglycine or D-dihydrobenzene Glycine and methanol were added to the reaction tank at a ratio of 1g: 3~5mL, and after stirring evenly, slowly added thionyl chloride; (b) reflux reaction after the addition of thionyl chloride; (c) vacuum distillation, Then cool down and crystallize, centrifuge and dry to obtain a white product; (d) recover the reaction mother liquor, concentrate the mother liquor in a vacuum, cool down and crystallize, and centrifuge to obtain a yellow recovered product; (e) wash the yellow recovered product with an organic reagent, and dry it in a vacuum to obtain White recycled product; (f) Apply the white recycled product to the reaction tank, and then follow steps (a)~(c) to prepare the next batch of products. The invention proposes a new way of applying the mother liquor, so that the product quality is more stable, the purity is high, and the color grade and turbidity are excellent.

The invention discloses a method for preparing amoxicillin or ampicillin in a full-water-phase through mode. The method includes the steps that a high-concentration penicillin GK or penicillin VK extracting solution is used as a raw material, immobilized penicillin G acylase or penicillin V acylase is used as an enzyme catalyst, a high-concentration 6-APA solution or crystal is obtained through full-water-phase operations such as catalytic cracking, separating, acidization, filtering, chromatography and concentration by nanofiltration, and then the amoxicillin or the ampicillin is synthesized by the solution or crystal and HPGME or phenylglycine methyl ester under the catalytic action of the immobilized penicillin synthetase. According to the method, water-phase reacting is conducted in the whole process, no organic solvent is used, and environmental pollution is reduced; besides, the special immobilized penicillin G acylase and the penicillin V acylase are used for cracking the high-concentration penicillin GK or VK extracting solution, and special macroporous absorption resin is used for separating and cracking products, so that the processing steps are greatly simplified, the production cost is lowered, the product yield is increased, and the industrial production requirement is met.

The invention discloses a method for preparing cefaclor from an enzyme process. The method comprises the following steps: preparing cefaclor coarse powder from 7-amino-3-chloro-cephem acid, D-o-phenylglycine methyl ester hydrochloride, immobilized cefaclor synthetase and cefaclor crystal seed; dissolving and discoloring the cefaclor coarse powder, adding the cefaclor crystal seed to regulate the pH value, stirring for a first time to grow the grains, and stirring for a second time to grow the grains after regulating the pH value, thereby preparing a crystal mixed solution; performing the suction filtration on the crystal mixed solution to obtain a crystal product and crystallized mother liquor; and sequentially performing washing with water, soaking washing, suction filtration and vacuum drying on the crystal product to obtain cefaclor. The method for preparing cefaclor from the enzyme process has twice stirring grain-growing operation, and the cefaclor slowly separates out in a re-crystallizing process, and the prepared crystal is uniform and is better in crystalline form; and the prepared cefaclor has very high purity greater than 99.7%.

The invention belongs to the technical field of the chemical industry, and in particular relates to a preparation process of D-phenylglycine methyl ester hydrochloride crystals. The preparation process comprises the following steps: sequentially adding methanol and D-phenylglycine into a reactor, stirring uniformly, and slowly adding sulfoxide chloride; controlling the temperature in the reactor below 55DEG C, and controlling the temperature in the reactor to be 55-65DEG C after adding sulfoxide chloride; performing reflux reaction, then performing vacuum azeotropic distillation, and finally performing temperature controlled cooling crystallization; and filtering, washing and drying to obtain a D-phenylglycine methyl ester hydrochloride crystal product. The preparation process provided by the invention is high in one-pass yield, the prepared product is high in purity, good in color grade and stable in quality, the preparation process is low in production cost, and the operation is easy to control.

The invention relates to the pharmaceutical field and provides a method for preparing ampicillin and a product obtained by the method. The method comprises the following steps: 1) mixing 6-APA and D-phenylglycine methyl ester or salt thereof in water and adding into ampicillin synthase at the temperature of 0 DEG C-30 DEG C, and reacting at the pH value of 5.5-7.5 and the temperature of 10 DEG C-30 DEG C; 2) adjusting the product obtained in the step 1) with acid till solution is clear, and keeping the pH value at 0.5-2.0 and the temperature at 10 DEG C-30 DEG C; 3) cooling the solution obtained in the step 2) to 12 DEG C-15 DEG C, then regulating the pH value to 3.00-3.50, further cooling to 5 DEG C-6 DEG C, and maintaining the pH value at 3.50; then, adjusting the pH value to 4.9-5.0, cooling to 1 DEG C-2 DEG C, and keeping so as to obtain ampicillin crystals. By adopting the method provided by the invention, the yield and quality of ampicillin products are greatly upgraded, the production efficiency is improved, and the medication safety of the ampicillin products is further ensured.