William J. Hennen

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.