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Upstream product

• 371-27-7 2,2,2-trifluoroethylbutyrate 
• 93-54-9 1-Phenyl-1-propanol 
• 123-20-6 vinyl n-butyrate 

Relevant academic research and scientific papers

Optimization of lipase-catalyzed enantioselective production of 1-phenyl 1-propanol using response surface methodology

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.

Improved Enantioselectivity of Subtilisin Carlsberg towards Secondary Alcohols by Protein Engineering

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.

Ionic-surfactant-coated subtilisin: Activity, enantioselectivity, and application to dynamic kinetic resolution of secondary alcohols

In this work, we explored the utility of ionic-surfactant-coated Bacillus licheniformis subtilisin (ISCBLS) as the catalyst for the dynamic kinetic resolution of secondary alcohols. ISCBLS was prepared by freeze-drying Bacillus licheniformis subtilisin wi

Combinatorial library based engineering of candida antarctica lipase a for enantioselective transacylation of sec-alcohols in organic solvent

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)

Enantioselective transesterification catalysis by nanosized serine protease subtilisin Carlsberg particles in tetrahydrofuran

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.

An S-selective lipase was created by rational redesign and the enantioselectivity increased with temperature

(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

Enzyme Reactions in Apolar Solvent. 5. The Effect of Adjacent Unsaturation on the PPL-Catalyzed Kinetic Resolution of Secondary Alcohols

The effect of adjacent unsaturation on the enzyme-catalyzed kinetic resolution of secondary alcohols is studied for a series of allylic, homoallylic, propargylic, homopropargylic, and phenyl-substituted 2-alkanols, using porcine pancreatic lipase (PPL) in anhydrous Et2O.Excellent enantioselectivity (high E value) was observed for α-phenethyl alcohol (3), propargylic alcohols (8 and 11), and (E)-allylic alcohols (9 and 12), but (Z)-allylic alcohols (10 and 13) showed poor selectivity.Enantioselectivity was also low for both (E)- and (Z)-homoallylic alcohols (15 and 16), homopropargylic alcohol (14), 1-phenyl-2-propanol (6), and 4-phenyl- 2-butanol (7).The enhanced enantioselectivity observed for (E)-allylic alcohols was exploited in the synthesis of the enantiomers of both components of the aggregation pheromone of the lesser grain borer, Rhyzopertha dominica (F.).The magnitude of the enantiomeric ratio (E value) can be dramatically affected by the accuracy of the values of ees and eep used in the calculation, especially when E is large.Variation in the value of E with the optical purity of the chiral derivatizing agent used to determine ees and eep is illustrated.