Enzymatic Transformations Biocatalysis

Asymmetric syntheses are ubiquitous in nature, and some of nature s catalysts have been exploited by chemists for use in the laboratory. Enzymes are proteins that can be isolated from natural sources and can be used to catalyze certain chemical transformations. Often, one enantiotopic group on a starting material will react preferentially. Alternatively, only one enantiomer of a racemic starting material will undergo a reaction (called a kinetic resolution), 

Predict the major product(s),paying close attention to the stereochemistry of each reaction product. 

For each of the following compounds, predict the possible monochlorination products (imagine reacting each with CI2, hv). Consider all regioiso-mers and stereoisomers. 

Introduction to Strategies for Organic Synthesis, First Edition. Laurie S. Starkey. 2012 John Wiley Sons, Inc. Published 2012 by John Wiley Sons, Inc. 

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Although enzymes are an important class of enantioselective catalysts, a systematic coverage of biocatalysis was beyond the scope of this work. However, the reader should be aware that biocatalysts can be an attractive alternative to synthetic chiral catalysts and in many chapters, references to related enzymatic transformations are given. An important new addition to biocatalysis are catalytic antibodies and their use for enantioselective transformations is summarized in chapter 40. 

Another category of enzymatic transformations in multiphase systems is enzymes immobilized on the reactor wall as presented in Table 10.4. Enzymes are advantageously used in immobilized form because this strategy allows for increased volumetric productivity and improves stability. Continuous mode of operation is employed in these systems. The approaches commonly used for immobilization in conventional multiphase biocatalysis can also be employed in microreactors such as covalent methods, cross-linked enzyme aggregates (CLEA), and adsorption methods. The experimental setups can either be chip-type reactors with activated charmel surface walls where enzyme binds, or enzyme immobilized monolith reactors, where a support is packed inside a capillary tube. 

In some cases, substrates and enzymes are not soluble in the same solvent. To achieve efficient substrate conversion, a large interface between the immiscible fluids has to be established, by the formation of microemulsions or multiple-phase flow that can be conveniently obtained in microfluidic devices. Until now only a couple of examples are published in which a two-phase flow is used for biocatalysis. Goto and coworkers [431] were first to study an enzymatic reaction in a two-phase flow in a microfluidic device, in which the oxidation ofp-chlorophenol by the enzyme laccase (lignin peroxidase) was analyzed (Scheme 4.106). The surface-active enzyme was solubilized in a succinic acid aqueous buffer and the substrate (p-chlorophenol) was dissolved in isooctane. The transformation ofp-chlorophenol occurred mainly at... 

Wong, C. H., Enzymatic catalysts in organic synthesis. Science, 244, 1145-1152. Faber, K. and Franssen, M. C. R., Prospects for the increased application of biocatalysts in organic transformations. Trends Biotechnol., 11, 461-470, 1989. Kvittingen, L., Some aspects of biocatalysis in organic solvents. Tetrahedron, 50, 8253-8274, 1994. 

Promote investigations in biocatalysis, enzymatic, and microbiological transformations ... 

An important analytical application of enzymatic microreactors is their use in biocatalysis, in order to transform a difficult-to-measure analyte into an easily measurable form. This could be represented by microreactors designed for digestion of proteins to convert them to more readily measured peptides. Applications of microreactors in continuous-flow chemistry have expanded rapidly over the past two decades, with numerous reports of higher conversions and yields compared to conventional batch equipment. In this chapter, a comprehensive discussion on the most recent trends in the development of enzymatic microreactors and their current applications are covered. 

Biocatalysis in organic synthesis has a longstanding history and wide applicability in the enantioselective reduction of ketones (150, 151], Many enzymatic protocols provide reliable, scalable, and inexpensive routes to optically active alcohols consequently, such transformations have been extensively employed in industrial applications. A few representative examples of enzymatic reductions of ketones on large scale, giving hydroxy acids 243 [147, 152) and 245 (153) with exceptional enantioselectivities and yields, are shown below (Equations 18 and 19). 

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