- Reshaping the active pocket of esterase Est816 for resolution of economically important racemates
-
Bacterial esterases are potential biocatalysts for the production of optically pure compounds. However, the substrate promiscuity and chiral selectivity of esterases usually have a negative correlation, which limits their commercial value. Herein, an efficient and versatile esterase (Est816) was identified as a promising catalyst for the hydrolysis of a wide range of economically important substrates with low enantioselectivity. We rationally designed several variants with up to 11-fold increased catalytic efficiency towards ethyl 2-arylpropionates, mostly retaining the initial substrate scope and enantioselectivity. These variants provided a dramatic increase in efficiency for biocatalytic applications. Based on the best variant Est816-M1, several variants with higher or inverted enantioselectivity were designed through careful analysis of the structural information and molecular docking. Two stereoselectively complementary mutants, Est816-M3 and Est816-M4, successfully overcame and even reversed the low enantioselectivity, and several 2-arylpropionic acid derivatives with highEvalues were obtained. Our results offer potential industrial biocatalysts for the preparation of structurally diverse chiral carboxylic acids and further lay the foundation for improving the catalytic efficiency and enantioselectivity of esterases.
- Liu, Xiaolong,Zhao, Meng,Fan, Xinjiong,Fu, Yao
-
p. 6126 - 6133
(2021/09/28)
-
- Applications of micro-channel reactor in zaltoprofen cyclization reaction, and zaltoprofen cyclization method
-
The invention belongs to the technical field of pharmaceutical synthesis, and specifically discloses a zaltoprofen cyclization method and applications of a micro-channel reactor in a zaltoprofen cyclization process. According to the present invention, cyclization is performed in a micro-channel reactor, and the uniformly stirred material is heated to a temperature of 60-70 DEG C before the material enters the micro-channel reactor, wherein the reaction temperature is 60-90 DEG C, the flow rate is controlled at 5-10 ml/min, the pressure drop is 6 bar, the material passing time is 5-10 s, and amass ratio of a zaltoprofen intermediate II 5-(2-propionyloxy)-2-phenylthiophenylacetic acid to polyphosphoric acid to phosphoric acid is 1:3-4:0.5. According to the present invention, by using the micro-channel reactor, the cyclization yield can be substantially increased, the reaction time can be shortened, the product quality can be stabilized, the post-treatment difficulty can be substantiallyreduced, and the pollution degree can be substantially improved.
- -
-
Paragraph 0010-0012
(2019/11/20)
-
- Cu(ii)-catalyzed sulfide construction: both aryl groups utilization of intermolecular and intramolecular diaryliodonium salt
-
A sulfur-iodine exchange protocol of diaryliodonium salts with inorganic sulfur salt was developed. Both aryl groups in the diaryliodonium salt were fully exerted in this transformation. Five- to eight-membered sulfur-containing heterocycles were achieved. Note that [1]benzothieno-[3,2-b][1]benzothiophene (BTBT) (an organic field-effect transistor (OFET) material) and Zaltoprofen were efficiently established through this method.
- Wang, Ming,Wei, Jianpeng,Fan, Qiaoling,Jiang, Xuefeng
-
p. 2918 - 2921
(2017/03/15)
-
- Diaryl thioether compound, and synthetic method and application thereof
-
The invention discloses a diaryl thioether compound, and a synthetic method and an application thereof. Various diaryl thioether compounds can be obtained through a reaction of a reaction raw material high iodine salt in dimethyl sulfoxide at 60-100DEG C under the action of an odorless sulfuration reagent, an alkali, a metal catalyst and a ligand for 3-12h. Sulfur is introduced in the later stage, so poisoning of sulfur to the metal catalyst and incompatibility of an oxidant in the early stage reaction are avoided; the above inorganic sulfur source is nontoxic and odorless; and two aryl groups in the high iodine salt are fully used, so the atom economy of the method is fully shown. The diaryl thioether compound prepared through the method can be further used to synthesize a photoelectric material BTBT and an anti-inflammatory drug zaltoprofen.
- -
-
Paragraph 0205-0209
(2018/02/04)
-
- A method for preparation of ibuprofen
-
The invention relates to a preparation method for Zaltoprofen, and discloses a method for preparing Zaltoprofen. The method comprises the following steps: using 5-(1-propionyl)-2-thiophenyl phenylacetic acid as an initiator; preparing the Zaltoprofen through rearrangement, hydrolysis and cyclization. The rearrangement of the 5-(1-propionyl)-2-thiophenyl phenylacetic acid adopts illumination to heat; the illumination function is embedded into atom, has an effect on electron, and reduces activation energy required by reaction; reaction efficiency is high; meanwhile, the illumination function enables iodine to sublimate into gas state; the iodine in gas state can be in contact with substrate fully; the reaction is more complete and quick; influence on the rearrangement reaction of methyl iodide is reduced; yield coefficient is higher; the method is simple to operate, environmentally friendly, and suitable for industrial production.
- -
-
Paragraph 0033; 0034; 0035-0039
(2016/10/07)
-
- Process for the preparation of ibuprofen (by machine translation)
-
The invention belongs to the field of preparation of non-steroidal anti-inflammatory drug, more specifically, relates to a process for the preparation of ibuprofen. Intermediates in the reactor (II) 5-(1-carboxyethyl) 2- benzene sulfur dimethylbenzene acetic acid with concentrated sulfuric acid, phosphoric acid mixed acid stirring reaction; at room temperature by adding ethyl acetate to the reaction solution, ice and water, collecting acetic acid ethyl ester level liquid, respectively for saturated sodium bicarbonate, sodium chloride solution, drying, distillation and condensation, the cooling crystallization, filtration, crystallization of the eluting with ethyl acetate, dried, ibuprofen products obtained. The preparation method is simple in operation, the utilization ratio of the raw material and the product yield, small influence on the environment, and is suitable for industrial production. (by machine translation)
- -
-
Paragraph 0018; 0019
(2016/12/01)
-
- METHOD FOR PRODUCING ZALTOPROFEN AND DERIVATIVE THEREOF
-
The present invention relates to a method for preparing zaltoprofen or a zaltoprofen derivative by a Friedel-Crafts reaction type intramolecular cyclization reaction in an industrial scale at an industrially acceptable yield and a purity sufficient for use as an active ingredient of medicaments in a simple and economical manner, without generating a detectable amount of impurities such as dimmers, by using polyphosphoric acid in an amount of 6.5 times or less of amount of a starting material compound before cyclization. More specifically, the present invention relates to such a method for preparing zaltoprofen or a zaltoprofen derivative as mentioned above, which comprises cyclizing a starting material compound before cyclization by an intramolecular cyclization reaction thereof in the presence of one or more kinds of organic solvents selected from the group consisting of 1,1,2-trichloroethene, methylcyclohexane, cyclohexane, n-heptane and the like.
- -
-
Paragraph 0081; 0082
(2015/03/16)
-
- OPTICAL ISOMER OF PHENYLPROPIONIC ACID AND ITS MEDICINAL USE
-
Optical isomers of phenylpropionic acid drugs are a mixture having R-type optical isomer and S-type optical isomer at a ratio of 10:1-1:10 by weight, wherein the ratio of 1:1 is excluded. A use of the optical isomers includes that the R-type optical isomer is used for manufacturing anti-inflammatory and analgesic drugs and the mixture having the R-type optical isomer and the S-type optical isomer at a ratio of 10:1-1:10 by weight, wherein the ratio of 1:1 is excluded, is used for manufacturing anti-inflammatory and analgesic drugs. The therapeutic indexes of anti-inflammatory and analgesic drugs of the present optical isomers are all higher than those of the S-type optical isomers and the racemate.
- -
-
Page/Page column 15
(2011/10/04)
-
- Preparation of 2-(10,11-dihydro-10-oxodibenzo-[b,f]thiepin-2-yl) propionic acid
-
PCT No. PCT/JP97/02922 Sec. 371 Date Feb. 17, 1999 Sec. 102(e) Date Feb. 17, 1999 PCT Filed Aug. 22, 1997 PCT Pub. No. WO98/07717 PCT Pub. Date Feb. 26, 1998A process for preparation of 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid (i.e., Zaltoprofen) is performed by subjecting 2-(4-amino-3-carboxy-methylphenyl)propionic acid or its salt to diazotization and subsequent reaction with thiophenol to produce 2-(3-carboxymethyl-4-phenylthiophenyl)propionic acid or its salt, and subjecting the product to cyclization reaction. Other related processes and related compounds are also disclosed.
- -
-
-
- Process for the preparation of dibenzothiepin derivative
-
A novel process for the preparation of 2-(10,11-dihydro-10-oxodibenzo[b, f]thiepin-2-yl)propionic acid which shows high anti-inflammatory and analgetic action is disclosed. The process starts from a propiophenone derivative having the formula (II): STR1 wherein R1 is hydrogen or a lower alkyl group, which is once converted into a haloacetal compound via a halo-ketone compound, and then converted into the desired dibenzothiepin derivative through a combination of rearrangement, hydrolysis and ring closure in variable sequences.
- -
-
-
- Process for the preparation of dibenzothiepin derivative
-
A novel process for the preparation of 2-(10,11--dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid which shows high anti-inflammatory and analgetic action is disclosed. The process starts from a propiophenone derivative having the formula (II): wherein R1 is hydrogen or a lower alkyl group, which is once converted into a haloacetal compound via a halo-ketone compound, and then converted into the desired dibenzothiepin derivative through a combination of rearrangement, hydrolysis and ring closure in variable sequences.
- -
-
-