72657-23-9Relevant academic research and scientific papers
A robust and stereocomplementary panel of ene-reductase variants for gram-scale asymmetric hydrogenation
Nett, Nathalie,Duewel, Sabine,Schmermund, Luca,Benary, Gerrit E.,Ranaghan, Kara,Mulholland, Adrian,Opperman, Diederik J.,Hoebenreich, Sabrina
, (2021/01/25)
We report an engineered panel of ene-reductases (ERs) from Thermus scotoductus SA-01 (TsER) that combines control over facial selectivity in the reduction of electron deficient C[dbnd]C double bonds with thermostability (up to 70 °C), organic solvent tolerance (up to 40 % v/v) and a broad substrate scope (23 compounds, three new to literature). Substrate acceptance and facial selectivity of 3-methylcyclohexenone was rationalized by crystallisation of TsER C25D/I67T and in silico docking. The TsER variant panel shows excellent enantiomeric excess (ee) and yields during bi-phasic preparative scale synthesis, with isolated yield of up to 93 % for 2R,5S-dihydrocarvone (3.6 g). Turnover frequencies (TOF) of approximately 40 000 h?1 were achieved, which are comparable to rates in hetero- and homogeneous metal catalysed hydrogenations. Preliminary batch reactions also demonstrated the reusability of the reaction system by consecutively removing the organic phase (n-pentane) for product removal and replacing with fresh substrate. Four consecutive batches yielded ca. 27 g L?1 R-levodione from a 45 mL aqueous reaction, containing less than 17 mg (10 μM) enzyme and the reaction only stopping because of acidification. The TsER variant panel provides a robust, highly active and stereocomplementary base for further exploitation as a tool in preparative organic synthesis.
Bombyx uterol ester (((R)-(-)-3-2- R) and its derivatives) and synthetic method thereof (by machine translation)
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Paragraph 0090-0093, (2019/11/29)
The invention discloses a synthetic method of ((R)- (-) - 3 - rhodanshi ester (R)-2-methyl) propionate (methyl propionate) and a derivative thereof. To the synthetic method disclosed by the (S)- 4 - invention, as a raw material, a series of reactions such as acylation, substitution, hydrolysis, esterification, hydrogenation and ((R)- (-) - 3 - the like are synthesized to synthesize the Rogoligoligoligoligosl)-methyl propionate and derivatives thereof. The synthesis method is equally applicable to the synthesis of its enantiomers and derivatives thereof. The method has the advantages of short reaction time, high yield, good chiral selectivity, suitability for industrial production and the like. The invention relates to a roshi ester and a derivative structure thereof. . (by machine translation)
Catalytic Asymmetric Construction of Halogenated Stereogenic Carbon Centers by Direct Vinylogous Mannich-Type Reaction
Zhong, Feng,Yue, Wen-Jun,Zhang, Hai-Jun,Zhang, Cheng-Yuan,Yin, Liang
supporting information, p. 15170 - 15175 (2018/11/30)
A catalytic asymmetric vinylogous Mannich-type reaction of γ-halo-α,β-unsaturated N-acylpyrazoles and N-Boc-aldimines was disclosed, which afforded an array of halogenated (F-, Cl-, and Br-) allylic stereogenic carbon centers in high yields with good to high regio-, diastereo-, and enantioselectivities. The brominated product served as a suitable electrophile for common SN2 nucleophilic substitution and copper-mediated SN2′ allylic alkylation with metal reagents. The utility of present methodology was demonstrated by the asymmetric synthesis of a common intermediate toward the synthesis of two chiral 2,3-disubstituted piperidine pharmaceuticals.
Revealing Additional Stereocomplementary Pairs of Old Yellow Enzymes by Rational Transfer of Engineered Residues
Nett, Nathalie,Duewel, Sabine,Richter, Alexandra Annelis,Hoebenreich, Sabrina
, p. 685 - 691 (2017/04/11)
Every year numerous protein engineering and directed evolution studies are published, increasing the knowledge that could be used by protein engineers. Here we test a protein engineering strategy that allows quick access to improved biocatalysts with very little screening effort. Conceptually it is assumed that engineered residues previously identified by rational and random methods induce similar improvements when transferred to family members. In an application to ene-reductases from the Old Yellow Enzyme (OYE) family, the newly created variants were tested with three compounds, revealing more stereocomplementary OYE pairs with potent turnover frequencies (up to 660 h?1) and excellent stereoselectivities (up to >99 %). Although systematic prediction of absolute enantioselectivity of OYE variants remains a challenge, “scaffold sampling” was confirmed as a promising addition to protein engineers' collection of strategies.
Cell-free protein engineering of Old Yellow Enzyme 1 from Saccharomyces pastorianus
Quertinmont, Leann T.,Lutz, Stefan
, p. 7282 - 7287 (2016/10/29)
In protein engineering, cell-free transcription/translation of linear mutagenic DNA templates can tremendously accelerate and simplify the screening of enzyme variants. Using the RApid Parallel Protein EvaluatoR (RAPPER) protocol, we have evaluated the impact of amino acid substitutions and loop truncations on substrate specificity and stereoselectivity of Old Yellow Enzyme 1 from Saccharomyces pastorianus. Our study demonstrates the benefit of systematically assessing amino acid variations including substrate profiling to explore sequence-function space.
Finding the Selectivity Switch - A Rational Approach towards Stereocomplementary Variants of the Ene Reductase YqjM
Rüthlein, Elisabeth,Classen, Thomas,Dobnikar, Lina,Sch?lzel, Melanie,Pietruszka, J?rg
supporting information, p. 1775 - 1786 (2015/06/02)
Ene reductases from the Old Yellow Enzyme family are versatile biocatalysts useful for the synthesis of optically active compounds. One disadvantage of biocatalysts when compared to competing catalysts in chemical syntheses is that often only one stereoisomer of the product is available. Another drawback can be the lack of activity in certain enzyme-substrate combinations. We were able to approach both of these challenges rationally in the case of the enzymatic synthesis of methyl 3-hydroxy-2-methylpropanoate (commonly denoted as the Roche ester) and derivatives thereof using the ene reductase YqjM. By a highly efficient, concept-based approach of designing mutant variants of YqjM and engineering substrates we could alter both the rate constant and the enantioselectivity of the reaction. Preparative scale reactions have been performed with successful mutants. In addition, the iterative modification of the substrate gave experiment-based insights into the binding mode of the Roche ester precursor and its derivatives.
Mild deprotection of PMB ethers using tert-butyl bromide
Rival, Nicolas,Albornoz Grados, Arantxa,Schiavo, Lucie,Colobert, Fran?oise,Hanquet, Gilles
, p. 6823 - 6826 (2015/11/27)
A convenient and high yielding method for the cleavage and scavenging of p-methoxybenzyl protecting group of several alcohols using tert-butyl bromide in refluxing acetonitrile is described. Under these mild conditions other protecting groups such as acid sensitive allyl, benzyl, and Me3CPh2Si ethers, or isopropylidene acetals were unchanged. Interestingly, a selective alkoxy-PMB cleavage was observed in the presence of a PMB phenoxy ether.
MaxPHOS ligand: PH/NH tautomerism and rhodium-catalyzed asymmetric hydrogenations
Cristobal-Lecina, Edgar,Etayo, Pablo,Doran, Sean,Reves, Marc,Martin-Gago, Pablo,Grabulosa, Arnald,Costantino, Andrea R.,Vidal-Ferran, Anton,Riera, Antoni,Verdaguer, Xavier
, p. 795 - 804 (2014/04/03)
MaxPHOS is an active and robust P-stereogenic ligand for asymmetric catalysis. The presence of an -NH- bridge between the two phosphine moieties allows the NH/PH tautomerism to take place. The neutral ligand, in which the NH form predominates, is an air-sensitive compound. However, protonation of MaxPHOS leads to the stable PH form of the ligand, in which the overall positive charge is distributed on both P centers. This protonation turns the MaxPHOS×HBF4 salt 3 into an air-stable compound both in the solid state and in solution. The salt 3 is also a convenient precursor for the preparation of rhodium(I) complexes by direct ligand exchange with the complex [Rh(acac)(cod)]. Finally, the corresponding rhodium(I)-MaxPHOS complex was tested in the asymmetric hydrogenation of a wide range of substrates. The complex proved to be a highly selective and robust system in these reactions.
Metal-organic framework Co(D-cam)1/2(bdc)1/2(tmdpy) for improved enantioseparations on a chiral cyclodextrin stationary phase in gas chromatography
Liu, Hong,Xie, Sheng-Ming,Ai, Ping,Zhang, Jun-Hui,Zhang, Mei,Yuan, Li-Ming
, p. 1103 - 1108 (2014/11/07)
Initial efforts to combine a chiral metal-organic framework (MOF), Co(D-Cam)1/2(bdc)1/2(tmdpy) (D-Cam=D-camphoric acid, bdc=1,4-benzenedicarboxylic acid, tmdpy=4,4′-trimethylenedipyridine), with peramylated β-cyclodextrins to investigate whether the use of a MOF can enhance enantioseparations on a cyclodextrin stationary phase are reported. Compared with columns of peramylated β-cyclodextrin incorporated in a MOF containing sodium chloride, the column of peramylated β-cyclodextrin+MOF shows excellent selectivity for the recognition of racemates, and higher resolutions are achieved on the peramylated β-cyclodextrin+MOF stationary phase. Experimental results indicate that the use of Co(D-Cam) 1/2(bdc)1/2(tmdpy) can improve enantioseparations on peramylated β-cyclodextrins. This is the first report that chiral MOFs can improve enantioseparations on a chiral stationary phase for chromatography. Copyright
P-CHIROGENIC ORGANOPHOSPHORUS COMPOUNDS
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Page/Page column 88; 89; 90, (2013/03/26)
The present invention relates to novel P-chirogenic organophosphorus compounds of general formula (I). The present invention also provides a process for the synthesis of said compounds of formula (I). The present invention also relates to intermediate products of general formulae (II), (III) and (IV), as shown below, which are involved in the synthesis of compounds (I). Further, the invention relates to metal complexes comprising compounds (I) as ligands. The novel compounds and complexes of the present invention are useful in asymmetric catalysis by transition metal complexes or organocatalysis, especially for asymmetric hydrogenation or allylation. Compounds of general formula (I) may useful as agrochemical and therapeutic substances, or as reagents or intermediates for fine chemistry.
