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Presidential Green Chemistry Challenge: 2000 Academic Award

Professor Chi-Huey Wong of The Scripps Research Institute


Enzymes in Large-Scale Organic Synthesis


Innovation and Benefits: Professor Wong developed methods to replace traditional reactions requiring toxic metals and hazardous solvents. His methods use enzymes, environmentally acceptable solvents, and mild reaction conditions. His methods also enable novel reactions that were otherwise impossible or impractical on an industrial scale. Professor Wong's methods hold promise for applications in a wide variety of chemical industries.

Summary of Technology: Organic synthesis has been one of the most successful of scientific disciplines and has contributed significantly to the development of the pharmaceutical and chemical industries. New synthetic reagents, catalysts, and processes have made possible the synthesis of molecules with varying degrees of complexity. The types of problems at which nonbiological organic synthesis has excelled, ranging from stoichiometric reactions to catalysis with acids, bases, and metals, will continue to be very important. New synthetic and catalytic methods are, however, necessary to deal with the new classes of compounds that are becoming the key targets of molecular research and development.

Compounds with polyfunctional groups such as carbohydrates and related structures pose particular challenges to nonbiological synthetic methods but are natural targets for biological methods. In addition, biological methods are necessary to deal with increasing environmental concerns. Transition metals, heavy elements, and toxic organic solvents are often used in nonbiological processes. When these materials are used with great care and efficiency, they may still be environmentally acceptable, but their handling and disposal pose problems. The ability to use recombinant and engineered enzymes to carry out environmentally acceptable synthetic transformations that are otherwise impossible or impractical offers one of the best opportunities now available to chemistry and the pharmaceutical industry.

Professor Chi-Huey Wong at the Scripps Research Institute has pioneered work on the development of effective enzymes and the design of novel substrates and processes for large-scale organic synthesis. The methods and strategies that Professor Wong has developed have made possible synthetic transformations that are otherwise impossible or impractical, especially in areas vitally important in biology and medicine, and have pointed the way toward new green methodologies for use in large-scale chemistry. A recent study by the Institute for Scientific Information ranked Professor Wong in the top 15 of the most-cited chemists in the world for the period 1994 to 1996. According to this study, he is also the most-cited chemist worldwide working in the area of enzymes.

Some of the strategies and methods developed by Professor Wong are breakthrough achievements that laid the framework for much of the current use of enzymes as catalysts in large-scale organic synthesis. The techniques and reagents developed in this body of pioneering work are used widely today for research and development. The scope of contributions ranges from relatively simple enzymatic processes (e.g., chiral resolutions and stereoselective syntheses) to complex, multistep enzymatic reactions (e.g., oligosaccharide synthesis). For example, the irreversible enzymatic transesterification reaction using enol esters in environmentally acceptable organic solvents invented by Professor Wong represents the most widely used method for enantioselective transformation of alcohols in pharmaceutical development. The multi-enzyme system based on genetically engineered glycosyltransferases coupled with in situ regeneration of sugar nucleotides developed by Professor Wong has revolutionized the field of carbohydrate chemistry and enabled the large-scale synthesis of complex oligosaccharides for clinical evaluation. All of these new enzymatic reactions are carried out in environmentally acceptable solvents, under mild reaction conditions, at ambient temperature, and with minimum protection of functional groups. The work of Professor Wong represents a new field of green chemistry suitable for large-scale synthesis that is impossible or impractical to achieve by nonenzymatic means.

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