40628-81-7Relevant academic research and scientific papers
Rh-catalyzed asymmetric hydrogenation of α-aryl-β-alkylvinyl esters with chiral ferrocenylphosphine-phosphoramidite ligand
Dong, Chao,Liu, Dao-Sheng,Zhang, Lei,Hu, Xiang-Ping
supporting information, (2021/02/03)
An enantioselective Rh-catalyzed hydrogenation of E/Z mixtures of trisubstituted vinyl esters has been disclosed. With a combination of [Rh(COD)2]BF4 and a structurally fine-tuning chiral ferrocenylphosphine-phosphoramidite ligand as the catalyst, a variety of E/Z mixtures of α-aryl-β-alkylvinyl esters have been successfully hydrogenated in high yields and with good to high enantioselectivities (up to 96% ee). The presence of a small amount of tBuOH proved to be beneficial to improve the hydrogenation outcome.
Highly Focused Library-Based Engineering of Candida antarctica Lipase B with (S)-Selectivity Towards sec-Alcohols
Cen, Yixin,Li, Danyang,Xu, Jian,Wu, Qiongsi,Wu, Qi,Lin, Xianfu
supporting information, p. 126 - 134 (2018/12/05)
Candida antarctica lipase B (CALB) is one of the most extensively used biocatalysts in both academia and industry and exhibits remarkable (R)-enantioselectivity for various chiral sec-alcohols. Considering the significance of tailor-made stereoselectivity in organic synthesis, a discovery of enantiocomplementary lipase mutants with high (R)- and (S)-selectivity is valuable and highly desired. Herein, we report a highly efficient directed evolution strategy, using only 4 representative amino acids, namely, alanine (A), leucine (L), lysine (K), tryptophan (W) at each mutated site to create an extremely small library of CALB variants requiring notably less screening. The obtained best mutant with three mutations W104V/A281L/A282K displayed highly reversed (S)-selectivity towards a series of sec-alcohol with E values up to 115 (conv. 50%, ee 94%). Compared with the previously reported (S)-selective CALB variant, W104A, a single mutation provided less selectivity, while the synergistic effects of three mutations in the best variant endow better (S)-selectivity and a broader substrate scope than the W104A variant. Structural analysis and molecular dynamics simulation unveiled the source of reversed enantioselectivity. (Figure presented.).
Acetate compound synthesis method
-
Paragraph 0089-0095, (2020/01/03)
The invention provides an acetate compound synthesis method, and belongs to the field of organic synthesis, wherein the synthesis method has advantages of simple reaction system, no requirement of additional metal catalysts, no requirement of heating, high reaction and efficient synthesis of acetate compounds. According to the technical scheme, the preparation method comprises: respectively addinga styrene compound, an iodoalkyl compound and sodium acetate into a reactor, and carrying out an irradiation reaction for 2-10 h at a room temperature of 20-25 DEG C under a 10 W white daylight lampunder the actions of DDQ and ethanol; and after the reaction is finished, carrying out column chromatography separation to obtain the acetate compound. The method of the invention can be used in synthesis experiments of acetate compounds.
Substrate specificity of an esterase from the archaeon Sulfolobus tokodaii bearing a GGG(A)X motif
Wada, Reina,Ozaki, Masanaru,Kumon, Takashi,Ohta, Hiromichi,Miyamoto, Kenji
, p. 188 - 190 (2015/11/09)
A GGG(A)X-type esterase (Est0071) from an archaeon catalyzes asymmetric hydrolysis of prochiral bulky malonic diesters in good enantioselectivity. The selectivity of Est0071 was for the opposite enantiomer to that previously shown for pig liver esterase, and the resulting enantiomeric excess of the products was higher. Est0071 could also catalyze the hydrolysis of various acetates of secondary alcohols, and showed moderate enantioselectivity in these reactions.
A novel lipase enzyme panel exhibiting superior activity and selectivity over lipase B from Candida antarctica for the kinetic resolution of secondary alcohols
O'Neill, Maeve,Beecher, Denis,Mangan, David,Rowan, Andrew S.,Monte, Agnieszka,Sroka, Stefan,Modregger, Jan,Hundle, Bhupinder,Moody, Thomas S.
experimental part, p. 583 - 586 (2012/08/13)
A novel, commercially available lipase enzyme panel performing kinetic bioresolutions of a number of secondary alcohols is reported. The secondary alcohols that have been chosen are known from the literature to be particularly challenging substrates to resolve. Following initial screening, four co-solvents were investigated for each lead enzyme in an effort to assess their tolerance to common organic solvents. The superiority of these novel enzymes over lipase B from Candida antarctica (CALB) has been demonstrated.
Mutant lipase-catalyzed kinetic resolution of bulky phenyl alkyl sec-alcohols: A thermodynamic analysis of enantioselectivity
Vallin, Michaela,Syren, Per-Olof,Hult, Karl
experimental part, p. 411 - 416 (2010/12/19)
The size of the stereoselectivity pocket of Candida antarctica lipase B limits the range of alcohols that can be resolved with this enzyme. These steric constrains have been changed by increasing the size of the pocket by the mutation W104A. The mutated enzyme has good activity and enantioselectivity toward bulky secondary alcohols, such as 1-phenylalkanols, with alkyl chains up to eight carbon atoms. The S enantiomer was preferred in contrast to the wild-type enzyme, which has R selectivity. The magnitude of the enantioselectivity changes in an interesting way with the chain length of the alkyl moiety. It is governed by interplay between entropic and enthalpic contributions and substrates with long alkyl chains are resolved best with E values higher than 100. The enantioselectivity increases with temperature for the small substrates, but decreases for the long ones.
Study of the enantioselectivity of the CAL-B-catalysed transesterification of α-substituted α-propylmethanols and α-substituted benzyl alcohols
Garcia-Urdiales, Eduardo,Rebolledo, Francisca,Gotor, Vicente
, p. 3047 - 3052 (2007/10/03)
A study of the enantioselectivity exhibited by the lipase B from Candida antarctica in the transesterification of different α-substituted α-propylmethanols with vinyl acetate is shown. The best results are obtained when the large-sized (L) substituent of the alcohol is either a phenyl group or more especially a cyclohexyl group, although the reaction rates are lower than when linear or slightly branched groups are present. It is also found that ramification at the β-position of the L substituent has a deleterious effect on both lipase activity and enantioselectivity. Moreover, some α-substituted benzyl alcohols bearing medium-sized (M) substituents larger than an ethyl and smaller than a propyl group are resolved by means of this methodology with moderate-good enantioselectivities (E=46-57) and similar reaction rates.
Kinetic Resolution of (±)-1-Phenylbutan-1-ol by Means of CALB-Catalyzed Aminolyses: A Study on the Role of the Amine in the Alcohol Resolution
Garci?a-Urdiales, Eduardo,Rebolledo, Francisca,Gotor, Vicente
, p. 646 - 654 (2007/10/03)
The kinetic resolution of (±)-1-phenylbutan-1-ol [(±)-1] by means of CALB-catalyzed aminolysis of its acetyl derivative [(±)-2] using (±)-1-phenylethanamine [(±)-3] as nucleophile is a slower but more enantioselective process (E = 50) than the corresponding CALB-catalyzed transesterification of (±)-1 with vinyl acetate (E = 19). The use of triethylamine and acetanilide as additives in the transesterification of (±)-1 enhanced the enantiomeric ratio (E = 43 and 38, respectively), thus showing that both the basic character of the amine as well as its structural nature could be responsible for the enantioselectivity differences observed between the transesterification and aminolysis reactions. We have also carried out the aminolysis of (±)-2 using different chiral and non-chiral amines. Enantiomeric ratio values varied significantly with the amine employed, but the enzyme always remained more selective towards the R-enantiomer of the substrate. Among all the amines tested, (±)-1-phenylpropan-1-amine [(±)-5] was the nucleophile of choice. Analysis of the conversion values for each enantiomer of (±)-2 showed that the selectivity differences exhibited by the lipase in the aminolysis reactions were due to the different stabilization of the fast-reacting enantiomer of the substrate [(R)-2] during the catalytic process. The CALB behavior in these reactions could be explained on the basis of substrate imprinting effects, which were corroborated by means of enzyme recycling experiments. Finally, a solvent screening allowed the kinetic resolution of this alcohol for synthetic purposes.
