Yi-Fong Wang

Lipase-catalyzed irreversible transesterification using enol esters: Resolution of cyanohydrins and syntheses of ethyl (R)-2-hydroxy-4-phenylbutyrate and (S)-propranolol

Abstract Procedures for the resolution of several cyanohydrins of synthetic value via lipase-catalyzed kinetic resolution using enol esters as irreversible transesterification reagents are developed and the syntheses of ethyl (R)-2-hydroxy-4-phenylbutyrate and (S)-propranolol from enantiomerically pure cyanohydrins are demonstrated.

Lipase-catalyzed irreversible transesterification using enol esters: XAD-8 immobilized lipoprotein lipase-catalyzed resolution of secondary alcohols

Abstract Procedures for the preparation of XAD-8 immobilized lipoprotein lipase and the resolution of secondary alcohols of synthetic value in organic solvents using this immobilized enzyme have been developed.

Enzymatic catalysis in organic synthesis.

Publisher Summary This chapter describes the fundamental concepts and the practical aspects regarding the design and development of enzymatic catalysts for synthetic organic transformations. The rate acceleration and specificity of enzymatic reactions that operate under mild conditions are the major advantages of enzymes used in organic synthesis. According to transition state theory and the thermodynamic cycle, in a given enzyme-catalyzed reaction the catalyst binds to the reaction transition state more strongly than to the ground state substrate by a factor approximately equal to the rate acceleration. All types of catalysis in enzymatic reactions, such as acid-base catalysis, nucleophilic–electrophilic catalysis, and catalysis by approximation, strain, and distortion, are just the contributing factors that lead to reducing the transition state energy. Enzyme-catalyzed organic reactions have been extended from the synthesis of chiral synthons and low molecular weight substances such as sugars and peptides to more complex molecules such as oligosaccharides, polypeptides, nucleotides, and their conjugates. All recombinant DNA work today requires several key enzymatic reactions to construct the gene for the expression of a desired protein. The recombinant DNA technology, however, has made possible the low-cost production of enzymes and the rational alteration of enzymatic properties. The area of enzymatic catalysis is further stimulated by the exciting new discovery of catalytically active antibodies. With the increasing environmental concerns and regulatory constraints faced in the chemical and pharmaceutical industries, enzyme-based organic synthesis becomes an attractive alternative that may offer clean and mild catalytic processes for the synthesis of single stereoisomers.

A new NAD-dependent alcohol dehydrogenase with opposite facial selectivity useful for asymmetric reduction and cofactor regeneration

A new NAD-dependent alcohol dehydrogenase isolated from a Pseudomonas species catalysed the reduction of many acyclic ketones to optically active alcohols with very high enantioselectivity (90 to >98% enantiomeric excess); the stereochemical course of the reduction was determined to be the transfer of the pro-(R) hydrogen from NADH to the Si face of the carbonyl group, a process different from that for other known alcohol dehydrogenases.

Practical synthesis of carbohydrates based on aldolases and glycosyl transferases

With various recombinant DNA and protein engineering techniques now available, enzyme-bad technologies are emerging as practical methods for large-scale synthesis of chiral intermediates and bioactive molecules, especially carbohydrates, oligosaccharides, their conjugates and related substances. This paper describes recent developments in the synthesis of novel monosaccharides and aza sugars based on aldolases, and the synthesis of oligosaccharides and analogs based on glycosyltransferases coupled with in sins regeneration of sugar nucleotides. As many enzymes are available for the stereocontrolled synthesis of chiral synthons (l), attention has been extended to the development of more effective and stable enzymes for the synthesis of molecules with increasing complexity (2). One class of such complex molecules are carbohydrates and their conjugates, especially those that exist on cell surfaces (3). These molecules are involved in many types of recognition phenomena (3-6); however, most of their precise functions have not been clearly identified at the molecular level. Part of the reason is that these molecules have been difficult to isolate, characterize and synthesize. Enzyme-based technology seems to be well suited for the synthesis of glycoconjugates and related substances for the study of their functions as these molecules are multifunctional and highly soluble in polar solvents, and many enzymes are available for the transformation of these molecules (7). The following describes some new technologies developed for the synthesis of sugar- and peptide- related substances based on recombinant or engineered enzymes.