876389-40-1Relevant articles and documents
A recombinant ketoreductase tool-box. Assessing the substrate selectivity and stereoselectivity toward the reduction of β-ketoesters
Zhu, Dunming,Mukherjee, Chandrani,Rozzell, J. David,Kambourakis, Spiros,Hua, Ling
, p. 901 - 905 (2006)
The substrate selectivity and stereoselectivity of a series of ketoreductases were evaluated toward the reduction of two sets of β-ketoesters. Both the structural variety at β-position and the substituent at α-position greatly affected the activity and stereoselectivity of these ketoreductases. For the first set of β-ketoesters, at least one ketoreductase was found that catalyzed the formation of either (d) or (l) enantiomer of β-hydroxyesters from each substrate with high optical purity, with the only exception of ethyl (d)-3-hydroxy-3-phenylpropionate. For the second set of β-ketoesters with α-substituents, the situation is more complex. More commonly, a ketoreductase was found that formed one of the four diastereomers in optically pure form, with only a few cases in which enzymes could be found that formed two or more of the diastereomers in high optical purity. The continued development of new, more diverse ketoreductases will create the capability to produce a wider range of single diastereomers of 2-substituted-3-hydroxy acids and their derivatives.
Deracemization of diastereomerically pure syn- and anti-α-substituted β-hydroxyesters by Novozyme 435 lipase and determination of their absolute configuration by NMR spectroscopy
Barková, Kate?ina,Fuchs, Annett,Greif, Dieter,Herrmann, Corinna,Hofrichter, Martin,Pecyna, Marek Jan,Trapp, Christian
, (2021/06/03)
Enantiomerically pure α-substituted β-hydroxyesters are important chiral building blocks for ligands, auxiliaries and β-lactam antibiotics. A two-step chemo-enzymatic procedure using lipase as biocatalyst is an efficient way to synthesize such products. To date, the methods described are limited to molecules that do not contain a chiral center adjacent to the racemic carbinol, and furthermore, they are limited to acylation. Here, we investigated the deracemization of diastereomerically pure syn- and anti-α-substituted β-hydroxyesters containing two stereo centers, using experimental methods under neat conditions and classical molecule dynamics (MD) simulation. A screening of free and immobilized commercial lipases identified immobilized lipase B from Candida antarctica (Novozyme 435) as the most appropriate biocatalyst for sterically demanding α-substituted β-hydroxyesters. Using Novozyme 435, reaction conditions were optimized and hydroxyesters (3S) or (3R) were achieved with enantiomeric excesses up to ≥99% ee and maximum overall yields of 80%. The absolute configuration of the enantiomers was eventually determined by 1H-NMR spectroscopy after derivatization with MOSHER'S reagent (α-methoxy-α-trifluoromethylphenylacetic acid = MTPA).
