119141-89-8Relevant academic research and scientific papers
An efficient asymmetric approach to the R-enantiomer impurity of esomeprazole
Zhou, Guobin,Guan, Yueqing
, p. 17 - 19 (2016)
Esomeprazole {(S)-5-methoxy-2-[(4-methoxy-3, 5-dimethyl-2-pyridinylmethyl) sulfinyl]-1H-benzimidazole} is a proton pump inhibitor used as an antiulcer drug. Its R-enantiomer 3 was synthesized with high enantioselectivity by asymmetric oxidation of prochiral sulfide 2 using the oxaziridinium salt 4. Product 3, useful as a reference for the quality control of esomeprazole, was characterized by 1H and 13C NMR, IR, and HRMS. The enantiomeric excess was determined by HPLC.
Asymmetric Bio-oxidation Using Resting Cells of Rhodococcus rhodochrous ATCC 4276 Mutant QZ-3 for Preparation of (S)-Omeprazole in a Chloroform–Water Biphasic System Using Response Surface Methodology
Zhang, Yuanyuan,Lv, Kuiying,Deng, Yashan,Li, Huiling,Wang, Zhiyong,Li, Depeng,Gao, Xin,Wang, Fanye
, p. 2928 - 2938 (2021/02/01)
(S)-Omeprazole is a very effective anti-ulcer medicine that is difficult to be prepared using whole cells at elevated substrate concentrations. In the chloroform–water biphasic system, resting cells of the mutant QZ-3 of Rhodococcus rhodochrous (R. rhodochrous) ATCC 4276 were used to catalyze the bio-oxidation of omeprazole sulfide for preparation of (S)-omeprazole. Using response surface methodology (RSM), the reaction was optimized to work at a substrate concentration of 180?mM and a cell concentration of 100?g/L. The optimal yield of (S)-omeprazole obtained was 92.9% with enantiomeric excess (ee) (> 99%), and no sulfone by-product was detected under the optimal working conditions; reaction temperature 37?°C, pH 7.3 and reaction time, 43?h. A quadratic polynomial model was established, which predicts the experimental data with very high accuracy (R2 = 0.9990). The chloroform–water biphasic system may contribute to the significant improvement in substrate tolerance because almost all substrates are partitioned in the organic phase (water solubility of omeprazole sulfide is only about 0.5?mg/mL), resulting in little damage and inhibition to cells by substrates. The mutant QZ-3 of R. rhodochrous ATCC 4276 exhibited high enantioselectivity, activity and substrate and product tolerance. The aerated flask provides enough oxygen for a high concentration of cells. Accordingly, bio-oxidation is thus more promising for efficient preparation of chiral sulfoxides.
Method for preparing chiral sulfoxide drugs in water phase
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Paragraph 0039-0049, (2020/09/09)
The invention relates to the field of chiral drug preparation, in particular to a method for preparing chiral sulfoxide drugs in a water phase. The method for preparing the chiral sulfoxide drugs in the water phase comprises the following steps: using a hydrogen peroxide solution as oxidant, using a temperature-sensitive ferrocene chiral amino acid titanium complex as a catalyst and using prochiral thioether as a substrate in the pure water phase to perform an asymmetric oxidation reaction to synthesize the chiral sulfoxide drugs. The temperature-sensitive ferrocene chiral amino acid titaniumcomplex catalyst can be utilized to catalyze the asymmetric oxidation reaction of thioether in the pure water phase and has the characteristics of high catalytic efficiency and easy recovery of the catalyst.
Tartaric acid ester compound as well as preparation method and applications thereof
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Paragraph 0101-0106, (2019/03/29)
The invention discloses a compound shown in formula (I), wherein R1 and R2 are independently selected from optionally substituted C1-6 alkyl, optionally substituted C3-8 cycloalkyl, optionally substituted C6-14 aryl and optionally substituted -(CH2)m-C3-8 cycloalkyl or -(CH2)n Ar; and Ar denotes the optionally substituted C6-14 aryl. The compound can be used for preparing prazole drugs during thetitanium-catalyzed asymmetric oxidation of pyrazole sulfides. (img file='DDA0001401304200000011.TIF' wi='669' he='551'/).
Method for producing proton pump inhibitor compound having optical activity
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Page/Page column 12; 13, (2019/06/15)
A highly pure optically active proton pump inhibitor compound can be produced safely and inexpensively in a high yield and enantioselectivity by a method of producing an optically active sulfoxide of Formula 2 or a salt thereof, comprising oxidizing a sulfide of Formula 1 or a salt thereof with hydrogen peroxide using an iron salt in the presence of a chiral ligand of Formula 3; wherein A is CH or N; R1 is hydrogen atom, an alkyl optionally substituted by halogen(s), or an alkoxy optionally substituted by halogen(s); one to three R2 may exist, and each of R2 is independently an alkyl, a dialkylamino, or an alkoxy optionally substituted by halogen(s) or alkoxy(s); each of R3 is independently hydrogen atom, a halogen, cyano or the like; R4 is a tertiary alkyl; and * and ** represent respectively R configuration or S configuration.
Enzymatic kinetic resolution of chiral sulfoxides-an enantiocomplementary approach
Nosek, Vladimír,Mí?ek, Ji?í
supporting information, p. 10480 - 10483 (2019/09/07)
A new enzymatic assay for the preparation of chiral sulfoxides that is enantiocomplementary to the known (S)-enantiomer-reducing activity of methionine sulfoxide reductase A (MsrA) is described. To this end, we have utilized the enzyme DMSO reductase (DmsABC), recently discovered by us being highly upregulated in stationary phase E. coli bacteria.
A catalytic asymmetric oxidizing thioether preparation of chiral pharmaceutical method
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Paragraph 0038-0044, (2020/02/07)
The invention provides a preparation method of a chiral sulfoxide medicament though catalysis of asymmetric oxidation of sulfides compounds. A chiral complex formed by quadridentate nitrogen organic ligand and metal manganese compound as a catalyst and hydrogen peroxide as an oxidant are used for asymmetric catalytic oxidation of prochiral thioether compound, so as to obtain the corresponding chiral sulfoxide medicament compounds including S-omeprazole, S-lansoprazole, S-pantoprazole, S-rabeprazole, R-Modafinil and R-sulindac. The reaction has the advantages of cleaness, mild reaction conditions, high conversion rate and antipodal selectivity, and shows industrial prospects.
Oxidative kinetic resolution of heterocyclic sulfoxides with a porphyrin-inspired manganese complex by hydrogen peroxide
Yang, Jinchuang,Wang, Lianyue,Lv, Ying,Li, Ning,An, Yue,Gao, Shuang
supporting information, p. 156 - 159 (2017/12/15)
We have successfully reported here the low loading porphyrin-inspired high-valent manganese (IV)-oxo complex was applied in oxidative kinetic resolution (OKR) of racemic heterocyclic sulfoxides using the environmentally benign hydrogen peroxide for the first time. This approach allows for rapid OKR (0.5 h) of a variety of racemic sulfoxides (including pyridine, pyrimidine, pyrazine, thiazole, benzothiazole, thiophene) in excellent enantioselectivity (up to > 99% ee), simultaneously generating the corresponding sulfones in high yield (up to 80%). The catalytic system also showed an unexceptionable chemoselectivity for the sulfoxide substrates with hydroxyl groups in which only the sulfoxide group was oxidized. The practical utility of the method has been demonstrated in the OKR of gram-scale sulfoxides.
Baeyer-Villiger Monooxygenase-Mediated Synthesis of Esomeprazole As an Alternative for Kagan Sulfoxidation
Bong, Yong Koy,Song, Shiwei,Nazor, Jovana,Vogel, Michael,Widegren, Magnus,Smith, Derek,Collier, Steven J.,Wilson, Rob,Palanivel,Narayanaswamy, Karthik,Mijts, Ben,Clay, Michael D.,Fong, Ryan,Colbeck, Jeff,Appaswami, Amritha,Muley, Sheela,Zhu, Jun,Zhang, Xiyun,Liang, Jack,Entwistle, David
, p. 7453 - 7458 (2018/07/29)
A wild-type Baeyer-Villiger monooxygenase was engineered to overcome numerous liabilities in order to mediate a commercial oxidation of pyrmetazole to esomeprazole, using air as the terminal oxidant in an almost exclusively aqueous reaction matrix. The developed enzyme and process compares favorably to the incumbent Kagan inspired chemocatalytic oxidation, as esomeprazole was isolated in 87% yield, in >99% purity, with an enantiomeric excess of >99%.
Esomeprazole as well as preparation method and application thereof
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Paragraph 0077; 0078; 0081; 0084; 0087; 0090; 0093, (2018/01/11)
The invention discloses esomeprazole as well as a preparation method and application thereof, relates to the technical field of medicines and aims to solve the technical problems that the existing preparation method of esomeprazole is low in economy and cannot meet the requirements of energy economization, consumption reduction, green and environment protection. The preparation method of the esomeprazole comprises a step of selectively oxidizing prochiral thioether ufiprazole into esomeprazole with cooperation of catalysts, oxidants, organic solvents and pH regulators under the action of functional chiral ionic liquid taking (D)-(-)-tartaric acid as anion. After the functional chiral ionic liquid taking (D)-(-)-tartaric acid as anion is added, the dissoluvability of the prochiral sulfide ufiprazole used as the raw material is obviously improved; the higher raw material utilization rate and selectivity can be ensured. The method has the advantages of simple step, easy operation, low consumption of solvents and low raw material dissolving temperature, so that the method is low in energy consumption, can meet the requirements of energy economization, consumption reduction, green and environment protection, and is suitable for large-scale industrial production.
