79121-13-4Relevant academic research and scientific papers
Stereodivergent Protein Engineering of a Lipase to Access All Possible Stereoisomers of Chiral Esters with Two Stereocenters
Xu, Jian,Cen, Yixin,Singh, Warispreet,Fan, Jiajie,Wu, Lian,Lin, Xianfu,Zhou, Jiahai,Huang, Meilan,Reetz, Manfred T.,Wu, Qi
supporting information, p. 7934 - 7945 (2019/05/22)
Enzymatic stereodivergent synthesis to access all possible product stereoisomers bearing multiple stereocenters is relatively undeveloped, although enzymes are being increasingly used in both academic and industrial areas. When two stereocenters and thus four stereoisomeric products are involved, obtaining stereodivergent enzyme mutants for individually accessing all four stereoisomers would be ideal. Although significant success has been achieved in directed evolution of enzymes in general, stereodivergent engineering of one enzyme into four highly stereocomplementary variants for obtaining the full complement of stereoisomers bearing multiple stereocenters remains a challenge. Using Candida antarctica lipase B (CALB) as a model, we report the protein engineering of this enzyme into four highly stereocomplementary variants needed for obtaining all four stereoisomers in transesterification reactions between racemic acids and racemic alcohols in organic solvents. By generating and screening less than 25 variants of each isomer, we achieved >90% selectivity for all of the four possible stereoisomers in the model reaction. This difficult feat was accomplished by developing a strategy dubbed "focused rational iterative site-specific mutagenesis" (FRISM) at sites lining the enzyme's binding pocket. The accumulation of single mutations by iterative site-specific mutagenesis using a restricted set of rationally chosen amino acids allows the formation of ultrasmall mutant libraries requiring minimal screening for stereoselectivity. The crystal structure of all stereodivergent CALB variants, flanked by MD simulations, uncovered the source of selectivity.
Resolution of secondary arylalkyl alcohols using pentafluorophenyl 2-phenylbutanoate and zinc chloride
Coulbeck, Elliot,Eames, Jason
experimental part, p. 4449 - 4451 (2009/12/01)
The resolution of racemic secondary arylalkyl alcohols using pentafluorophenyl 2-phenylbutanoate and zinc chloride is discussed. The levels of enantiomeric recognition were high leading to enantiomerically enriched alcohols in good yield.
Parallel kinetic resolution of racemic 1-phenylethanol using quasi-enantiomeric combinations of carboxylic acids mediated by N,N′-dicyclohexylcarbodiimide and 3,5-lutidine
Shaye, Najla Al,Boa, Andrew N.,Coulbeck, Elliot,Eames, Jason
, p. 4661 - 4665 (2008/12/20)
The parallel kinetic resolution of racemic 1-phenylethanol using an equimolar combination of quasi-enantiomeric 2-arylpropionic and butanoic acids mediated by a N,N′-dicyclohexylcarbodiimide (DCC)/3,5-lutidine coupling is discussed. The levels of diastereoselectivity were high leading to separable quasi-enantiomeric esters in good yield.
A versatile, practical, and inexpensive reagent, pyridine-3-carboxylic anhydride (3-PCA), for condensation reactions
Funasaka, Setsuo,Mukaiyama, Teruaki
experimental part, p. 148 - 159 (2009/04/06)
A highly useful method for the preparation of carboxylic esters and carboxamides from various carboxylic acids was established by using a novel condensing reagent, pyridine-3-carboxylic anhydride (3-PCA), in the presence of 4-(dimethylamino)pyridine as an activator. The reactions of various carboxylic acids with nucleophiles, such as alcohols or amines, afforded the corresponding carboxylic acids or carboxamides in good to high yields under mild conditions by using simple experimental procedure. In addition, it was confirmed that this protocol was applicable to a gram-scale synthesis and the by-products, including pyridine-3-carboxylic acid and pyridine-3-carboxylate (or pyridine-3- carboxamide) produced in situ, were easily removed by using a simple aqueous workup.
Parallel kinetic resolution of 1-phenylethanol using quasi-enantiomeric active esters
Coulbeck, Elliot,Eames, Jason
, p. 333 - 338 (2008/09/17)
The parallel kinetic resolution of racemic 1-phenylethanol using an equimolar combination of quasi-enantiomeric pentafluorophenyl esters is discussed. The levels of diastereoselectivity were excellent (>88% de) leading to separable quasi-enantiomeric esters in good yields. Georg Thieme Verlag Stuttgart.
Probing the parallel kinetic resolution of 1-phenylethanol using quasi-enantiomeric oxazolidinone adducts
Coulbeck, Elliot,Eames, Jason
, p. 2313 - 2325 (2008/03/18)
The parallel kinetic resolution of racemic 1-phenylethanol using an equimolar combination of quasi-enantiomeric oxazolidinones is discussed. The levels of diastereoselectivity were high leading to separable quasi-enantiomeric esters in good yield.
Highly efficient double enantioselection by lipase-catalyzed transesterification of (R,S)-carboxylic acid vinyl esters with (RS)-1- phenylethanol
Yang, Hong,Henke, Erik,Bornscheuer, Uwe T.
, p. 957 - 960 (2007/10/03)
Transesterification of the title compounds using lipase B from Candida antarctica in toluene afforded the corresponding esters in good to excellent diastereomeric excess. (R)-2-Phenylpropionic acid-(R)-1-phenethyl ester 4 was isolated in 45% yield and 64%
