Reaction Engineering in Asymmetric Synthesis

Stephan Liitz, Udo KragI, Andreas Liese, and Christian Wandrey 

The main task in technical application of asymmetric catalysis is to maximize catalytic efficiency, which can be expressed as the ttn (total turnover number, moles of product produced per moles of catalyst consumed) or biocatalyst consumption (grams of product per gram biocatalyst consumed, referring either to wet cell weight (wcw) or alternatively to cell dry weight (cdw)) [2]. One method of reducing the amount of catalyst consumed is to decouple the residence times of reactants and catalysts by means of retention or recycling of the precious catalyst. This leads to an increased exploitation of the catalyst in the synthesis reaction. 

Several methods can be employed to achieve the decoupling, namely immobilization (in a solid matrix or a second phase) or membrane filtration (Fig. 3.1.1) [2,3]. 

L-lactic add formation by fermentation of glucose or lactose with Lactobacilli enantioselective hydrocyanation 

L-aspartic acid by ammonia addition to fumaric acid by aspartase (from E. coli) 

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Systematic studies of topochemical reactions of organic solids have led to the possibility of asymmetric synthesis via reactions in chiral crystals. (A chiral crystal is one whose symmetry elements do not interrelate enantiomers.) (Green et al, 1979 Addadi et al, 1980). This essentially involves two steps (i) synthesis of achiral molecules that crystallize in chiral structures with suitable packing and orientation of reactive groups and (ii) performing a topochemical reaction such that chirality of crystals is transferred to products. The first step is essentially a part of the more general problem of crystal engineering. An example of such a system where almost quantitative asymmetric induction is achieved is the family of unsymmetrically substituted dienes ... 

Transaminases are important enzymes in the synthesis of chiral amines, amino acids, and amino alcohols, hi this chapter the properties of transaminases, the reaction mechanisms, and their selectivity and substrate specificity are presented. The synthesis of chiral building blocks for pharmaceutically relevant substances and fine chemicals with transaminases as biocatalysts is discussed. Enzymatic asymmetric synthesis and dynamic resolution are discussed using transaminases. Protein engineering by directed evolution as well as rational design of transaminases under process condition is presented to develop efficient bioprocesses. 

Darren J. Lipomi was bom in Rochester, New York, in 1983. He earned his BA in chemistry, with a minor in physics, from Boston University in 2005. Under Prof. James S. Panek, his research focused on the total synthesis of natural produas and asymmetric reaction methodology. He earned his AM and PhD in chemistry at Harvard University in 2008 and 2010, with Prof Geoi e M. Whitesides. At Harvard, he developed several unconventional approaches to fabricate micro- and nanostructures for electronic and optical applications. He is now an Intelligence Community Postdoctoral Fellow in the Department of Chemical Engineering at Stanford Univereity. 

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