113085-12-4Relevant articles and documents
Synthesis method of (S)-2-aryl propionate compound
-
Paragraph 0096-0099; 0120-0123, (2020/08/09)
The invention discloses a synthesis method of a (S)-2-aryl propionate compound. The (S)-2-aryl propionate compound shown in the formula IV is obtained by taking a compound shown in a formula I and a compound shown in a formula II as raw materials and reacting under the conditions of a chiral ligand shown in a formula III, a nickel catalyst, a photocatalyst, a reducing agent and alkali under the condition of visible light. The method has the advantages of cheap and easily available raw materials, convenient generation, mild conditions, environmental protection and safety, the photocatalyst canbe recycled, the production cost is greatly reduced, the test operation is simple, less waste is generated, and the method can be developed into an industrial production method.
Nickel/Photoredox-Catalyzed Asymmetric Reductive Cross-Coupling of Racemic α-Chloro Esters with Aryl Iodides
Guan, Haixing,Mao, Jianyou,Walsh, Patrick J.,Zhang, Qianwen
supporting information, p. 5172 - 5177 (2020/02/20)
A unique nickel/organic photoredox co-catalyzed asymmetric reductive cross-coupling between α-chloro esters and aryl iodides is developed. This cross-electrophile coupling reaction employs an organic reductant (Hantzsch ester), whereas most reductive cross-coupling reactions use stoichiometric metals. A diverse array of valuable α-aryl esters is formed under these conditions with high enantioselectivities (up to 94 %) and good yields (up to 88 %). α-Aryl esters represent an important family of nonsteroidal anti-inflammatory drugs. This novel synergistic strategy expands the scope of Ni-catalyzed reductive asymmetric cross-coupling reactions.
Towards sustainable kinetic resolution, a combination of bio-catalysis, flow chemistry and bio-based solvents
Iemhoff, Andree,Sherwood, James,McElroy, Con R.,Hunt, Andrew J.
supporting information, p. 136 - 140 (2018/01/17)
The esterification of 2-phenylpropionic acid was investigated as a model system for enzyme catalysed (CALB, Novozyme 435) reactions in bio-based solvents. A multi-parameter correlation taking into account solvent parameters was developed to explain experimental observations. A continuous flow process using p-cymene as the solvent was operated over several weeks, thus combining a sustainable solvent and flow chemistry for kinetic resolution.
Enantioselective Hydrogen Atom Transfer: Discovery of Catalytic Promiscuity in Flavin-Dependent 'Ene'-Reductases
Sandoval, Braddock A.,Meichan, Andrew J.,Hyster, Todd K.
supporting information, p. 11313 - 11316 (2017/08/30)
Flavin has long been known to function as a single electron reductant in biological settings, but this reactivity has rarely been observed with flavoproteins used in organic synthesis. Here we describe the discovery of an enantioselective radical dehalogenation pathway for α-bromoesters using flavin-dependent 'ene'-reductases. Mechanistic experiments support the role of flavin hydroquinone as a single electron reductant, flavin semiquinone as the hydrogen atom source, and the enzyme as the source of chirality.
Iron-Catalyzed Enantioselective Cross-Coupling Reactions of α-Chloroesters with Aryl Grignard Reagents
Jin, Masayoshi,Adak, Laksmikanta,Nakamura, Masaharu
supporting information, p. 7128 - 7134 (2015/06/25)
The first iron-catalyzed enantioselective cross-coupling reaction between an organometallic compound and an organic electrophile is reported. Synthetically versatile racemic α-chloro- and α-bromoalkanoates were coupled with aryl Grignard reagents in the presence of catalytic amounts of an iron salt and a chiral bisphosphine ligand, giving the products in high yields with acceptable and synthetically useful enantioselectivities (er up to 91:9). The produced α-arylalkanoates were readily converted to the corresponding α-arylalkanoic acids with high optical enrichment (er up to >99:1) via simple deprotections/recrystallizations. The results of radical probe experiments are consistent with a mechanism that involves the formation of an alkyl radical intermediate, which undergoes subsequent enantioconvergent arylation in an intermolecular manner. The developed asymmetric coupling offers not only facile and practical access to various chiral α-arylalkanoic acid derivatives, which are of significant pharmaceutical importance, but also a basis of controlling enantioselectivity in an iron-catalyzed organometallic transformation. (Chemical Equation Presented).
The organic-synthetic potential of recombinant Ene reductases: Substrate-Scope Evaluation and Process Optimization
Re?, Tina,Hummel, Werner,Hanlon, Steven P.,Iding, Hans,Gr?ger, Harald
, p. 1302 - 1311 (2015/04/27)
In this study an evaluation of the synthetic potential of a broad range of recombinant ene reductases was performed. In detail, a library of 23 ene reductases was used to screen the C=C reduction of 21 activated alkenes from different compound classes as substrates. The chosen set of substrates comprises nitroalkenes with an aryl substituent at the β-position and a methyl substituent at the α- or β-position, α,β-unsaturated carboxylic acids and their esters with and without substituents at the β-position, a range of cyclic α,β-unsaturated ketones with different ring sizes and substitution patterns and one α,β-unsaturated boronic acid. After we obtained insight into the substrate scope, several biotransformations were prioritised and further investigated in a screening of 41 reaction parameters (which included chaotropic and kosmotropic salts, polyols, buffer solutions, amino acids and organic solvents) towards their impact on the activity and enantioselectivity of the applied ene reductases. Under the optimised conditions, selected reduction processes were performed on an increased lab scale (up to 30 mL) with up to 10% substrate concentration, which led in general to both high conversion and (if chiral products were formed) enantioselectivity. Comprehensive screening: A detailed screening of 23 recombinant ene reductases for the reduction of 21 activated alkenes is performed as well as a subsequent study of the influence of 41 reaction parameters towards the enzyme activity and selectivity of selected reactions. In addition, a range of biocatalytic reductions on an increased laboratory scale are performed with substrate concentrations between 5 and 100 gL-1. EWG=Electron-withdrawing group.
Cobalt-bisoxazoline-catalyzed asymmetric kumada cross-coupling of racemic α-bromo esters with aryl grignard reagents
Mao, Jianyou,Liu, Feipeng,Wang, Min,Wu, Lin,Zheng, Bing,Liu, Shangzhong,Zhong, Jiangchun,Bian, Qinghua,Walsh, Patrick J.
supporting information, p. 17662 - 17668 (2015/02/02)
The first cobalt-catalyzed asymmetric Kumada cross-coupling with high enantioselectivity has been developed. The reaction affords a unique strategy for the enantioselective arylation of α-bromo esters catalyzed by a cobalt-bisoxazoline complex. A variety of chiral α-arylalkanoic esters were prepared in excellent enantioselectivity and yield (up to 97% ee and 96% yield). The arylated products were transformed into α-arylcarboxylic acids and primary alcohols without erosion of ee. The new enantioenriched α-arylpropionic esters synthesized herein are potentially useful in the development of nonsteroidal anti-inflammatory drugs. This method was conducted on gram-scale and applied to the synthesis of highly enantioenriched (S)-fenoprofen and (S)-ar-turmerone.
Laboratory evolution of enantiocomplementary Candida antarctica lipase B mutants with broad substrate scope
Wu, Qi,Soni, Pankaj,Reetz, Manfred T.
supporting information, p. 1872 - 1881 (2013/08/24)
Candida antarctica lipase B (CALB) is a robust and easily expressed enzyme used widely in academic and industrial laboratories with many different kinds of applications. In fine chemicals production, examples include acylating kinetic resolution of racemic secondary alcohols and amines as well as desymmetrization of prochiral diols (or the reverse hydrolytic reactions). However, in the case of hydrolytic kinetic resolution of esters or esterifying kinetic resolution of acids in which chirality resides in the carboxylic acid part of the substrate, rate and stereoselectivity are generally poor. In the present study, directed evolution based on iterative saturation mutagenesis was applied to solve the latter problem. Mutants with highly improved activity and enantioselectivity relative to wild-type CALB were evolved for the hydrolytic kinetic resolution of p-nitrophenyl 2-phenylpropanoate, with the selectivity factor increasing from E = 1.2 (S) to E = 72 (S) or reverting to E = 42 (R) on an optional basis. Surprisingly, point mutations both in the acyl and alcohol pockets of CALB proved to be necessary. Some of the evolved CALB mutants are also efficient biocatalysts in the kinetic resolution of other chiral esters without performing new mutagenesis experiments. Another noteworthy result concerns the finding that enantiocomplementary CALB mutants for α-substituted carboxylic acid esters also show stereocomplementarity in the hydrolytic kinetic resolution of esters derived from chiral secondary alcohols. Insight into the source of stereoselectivity was gained by molecular dynamics simulations and docking experiments.
Thermally driven asymmetric domino reaction catalyzed by a thermostable esterase and its variants
Wada, Reina,Kumon, Takashi,Kourist, Robert,Ohta, Hiromichi,Uemura, Daisuke,Yoshida, Shosuke,Miyamoto, Kenji
, p. 1921 - 1923 (2013/04/10)
We have developed a thermally driven domino reaction for the synthesis of (S)-a-arylpropionates (profens) using a thermostable esterase from Sulfolobus tokodaii strain 7. Stereoselectivity was improved considerably by engineering of the active site. Stereoselective decarboxylation at the active site of an esterase is a new reaction for the synthesis of optically active carboxylic acids. Crown Copyright.
Improvements of enzyme activity and enantioselectivity in lipase-catalyzed alcoholysis of (R,S)-azolides
Wu, An-Chi,Wang, Pei-Yun,Lin, Yi-Sheng,Kao, Min-Fang,Chen, Jin-Ru,Ciou, Jyun-Fen,Tsai, Shau-Wei
experimental part, p. 235 - 241 (2010/11/04)
With Candida antarctica lipase B (CALB)-catalyzed alcoholysis of (R,S)-naproxenyl 1,2,4-triazolide at the optimal conditions (i.e. anhydrous MTBE as the solvent, and methanol as the acyl acceptor at 45°C) as the model system, the enzyme enantioselectivity
