10031-86-4Relevant articles and documents
Shell Cross-Linked Micelles as Nanoreactors for Enantioselective Three-Step Tandem Catalysis
Kuepfert, Michael,Cohen, Aaron E.,Cullen, Olivia,Weck, Marcus
, p. 18648 - 18652 (2018)
Functionalized amphiphilic poly(2-oxazoline)-based triblock copolymers that assemble into shell cross-linked micelles (SCMs) are described. These micelles permit the site isolation of three incompatible catalysts through compartmentalization, thereby enabling three-step non-orthogonal tandem processes in one pot. In particular, the acid-catalyzed ketal hydrolysis to prochiral ketones proceeded in the hydrophilic corona, followed by the Rh-catalyzed asymmetric transfer hydrogenation to enantio-enriched alcohols in the cross-linked shell, and nucleophilic base-catalyzed acylation in the hydrophobic core. The catalysts are positioned in close proximity on a single micelle support to take advantage of the intramicellar substrate diffusion, yet they are sufficiently spaced apart from each other in physically distinct microenvironments. These compartmentalized micelles are substrate selective and, on a basic level, mimic compartmentalized catalytic architectures found in nature.
An S-selective lipase was created by rational redesign and the enantioselectivity increased with temperature
Magnusson, Anders O.,Takwa, Mohamad,Hamberg, Anders,Hult, Karl
, p. 4582 - 4585 (2005)
(Chemical Equation Presented) Higher activity with larger pockets: The figure shows a superposition of intermediates that occur in acyl transfer to (S)-1-phenylethanol catalyzed by Candida antarctica lipase B (CALB). Wild-type CALB cannot accomodate the p
Improved Enantioselectivity of Subtilisin Carlsberg towards Secondary Alcohols by Protein Engineering
Dorau, Robin,G?rbe, Tamás,Svedendahl Humble, Maria
, p. 338 - 346 (2017/12/26)
Generally, the catalytic activity of subtilisin Carlsberg (SC) for transacylation reactions with secondary alcohols in organic solvent is low. Enzyme immobilization and protein engineering was performed to improve the enantioselectivity of SC towards secondary alcohols. Possible amino-acid residues for mutagenesis were found by combining available literature data with molecular modeling. SC variants were created by site-directed mutagenesis and were evaluated for a model transacylation reaction containing 1-phenylethanol in THF. Variants showing high E values (>100) were found. However, the conversions were still low. A second mutation was made, and both the E values and conversions were increased. Relative to that shown by the wild type, the most successful variant, G165L/M221F, showed increased conversion (up to 36 %), enantioselectivity (E values up to 400), substrate scope, and stability in THF.
Combinatorial library based engineering of candida antarctica lipase a for enantioselective transacylation of sec-alcohols in organic solvent
Wikmark, Ylva,Svedendahl Humble, Maria,B?ckvall, Jan-E.
supporting information, p. 4284 - 4288 (2015/04/14)
A method for determining lipase enantioselectivity in the transacylation of sec-alcohols in organic solvent was developed. The method was applied to a model library of Candida antarctica lipase A (CalA) variants for improved enantioselectivity (E values)
Molecular recognition driven catalysis using polymeric nanoreactors
Cotanda, Pepa,O'Reilly, Rachel K.
supporting information, p. 10280 - 10282,3 (2020/09/09)
The concept of using polymeric micelles to catalyze organic reactions in water is presented and compared to surfactant based micelles in the context of molecular recognition. We report for the first time enzyme-like specific catalysis by tethering the catalyst in the well-defined hydrophobic core of a polymeric micelle.
Functionalized organocatalytic nanoreactors: Hydrophobic pockets for acylation reactions in water
Cotanda, Pepa,Lu, Annhelen,Patterson, Joseph P.,Petzetakis, Nikos,O'Reilly, Rachel K.
scheme or table, p. 2377 - 2384 (2012/06/29)
The effect of covalently attaching 4-(dimethylamino)pyridine (DMAP) functionality to the hydrophobic core of a polymeric micelle in water has been investigated in the context of acylation reactions employing non-water-soluble substrates. For this purpose a novel temperature-responsive polymeric micelle has been synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization techniques. The reactivity of the tethered organocatalyst within the nanostructure was found to be extremely high, improving in some cases the acylation rates up to 100 times compared to those for unsupported DMAP in organic solvents. Moreover, the catalytic nanoreactors have been demonstrated to be capable of reuse up to 6 times while maintaining high activity.
Enantioselective transesterification catalysis by nanosized serine protease subtilisin Carlsberg particles in tetrahydrofuran
Castillo, Betzaida,Delgado, Yamixa,Barletta, Gabriel,Griebenow, Kai
experimental part, p. 2175 - 2180 (2010/04/29)
Enzyme catalysis in organic solvents is a powerful tool for stereo-selective synthesis but the enantioselectivity is still hard to predict. To overcome this obstacle, we employed a nanoparticulate formulation of subtilisin Carlsberg (SC) and designed a series of 14 structurally related racemic alcohols. They were employed in the model transesterification reaction with vinyl butyrate and the enantioselectivities were determined. In general, short alcohol side chains led to low enantioselectivties, while larger and bulky side chains caused better discrimination of the enantiomers by the enzyme. With several bulky substrates high enantioselectivities with E>100 were obtained. Computational modeling highlighted that key to high enantioselectivity is the discrimination of the R and S substrates by the sole hydrophobic binding pocket based on their size and bulkiness. While bulky S enantiomer side chains could be accommodated within the binding pocket, bulky R enantiomer side chains could not. However, when also the S enantiomer side chain becomes too large and does not fit into the binding pocket anymore, enantioselectivity accordingly drops.
Optimization of lipase-catalyzed enantioselective production of 1-phenyl 1-propanol using response surface methodology
Soyer, Asl,Bayraktar, Emine,Mehmetoglu, Ulku
experimental part, p. 389 - 404 (2012/05/19)
Optically active 1-phenyl 1-propanol is used as a chiral building block and synthetic intermediate in the pharmaceutical industries. In this study, the enantioselective production of 1-phenyl 1-propanol was investigated systematically using response surface methodology (RSM). Before RSM was applied, the effects of the enzyme source, the type of acyl donor, and the type of solvent on the kinetic resolution of 1-phenyl 1-propanol were studied. The best results were obtained with Candida antartica lipase (commercially available as Novozym 435), vinyl laurate as the acyl donor, and isooctane as the solvent. In the RSM, substrate concentration, molar ratio of acyl donor to the substrate, amount of enzyme, temperature, and stirring rate were chosen as independent variables. The predicted optimum conditions for a higher enantiomeric excess (ee) were as follows: substrate concentration, 233mM; molar ratio of acyl donor to substrate, 1.5; enzyme amount, 116mg; temperature, 47°C; and stirring rate, 161rpm. A verification experiment conducted at these optimized conditions for maximum ee yielded 91% for 3hr, which is higher than the predicted value of 83%. The effect of microwave on the ee was also investigated and ee reached 87% at only 5min. Copyright Taylor & Francis Group, LLC.
Removal of the acyl donor residue allows the use of simple alkyl esters as acyl donors for the dynamic kinetic resolution of secondary alcohols
Verzijl, Gerard K.M.,De Vries, Johannes G.,Broxterman, Quirinus B.
, p. 1603 - 1610 (2007/10/03)
The dynamic kinetic resolution of secondary alcohols using a lipase and a ruthenium catalyst as developed by Baeckvall required some improvements to make it suitable for its use in an industrial process. The use of p-chlorophenyl acetate as acyl donor is not desirable in view of the toxicity of the side product. We herein report that simple alkyl esters can be used as acyl donors if the alcohol or ketone residue formed during the enzymatic acylation is continuously removed during the reaction. The addition of a ketone speeds up the racemisation process and allowed us to reduce the amounts of enzyme and ruthenium catalyst. The scope of this method was explored and a suitable range of acyl donors found. Various benzylic and aliphatic alcohols were reacted using isopropyl butyrate or methyl phenylacetate as acyl donor and in most cases the ester was isolated in >95% yield and 99% ee. Furthermore, it was demonstrated that the alcohol by-products of the enzymatic resolution could be used as the hydrogen source in the asymmetric reductive transesterification of ketones.
Biocatalysis in Organic Synthesis. 9. Highly Enantioselective Kinetic Resolution of Secondary Alcohols Catalyzed by Acylase
Faraldos, Juan,Arroyo, Elisa,Herradón, Bernardo
, p. 367 - 370 (2007/10/03)
A new catalytic activity of the enzyme acylase I (AA-I) from Aspergillus species has been found. Although this enzyme had previously been used only in the hydrolysis of N-acylamino acids, we have found that it is a highly efficient catalyst for transesterifications using vinyl esters as acyl donors. The method has been applied to the kinetic resolution of a variety of secondary alcohols.
