Enzymatic Asymmetric Reduction of Carbonyl Compounds

Typical LC molecules that exhibit SmC and/or SmCA phase are shown in Figure 1. As readily seen, the LC compounds consist of optically active 1,1,1-trifluoro-2-alkanols which contribute to the stabilization of the SmCA phase and thus play key roles of these LC materials. Accordingly methods for the l,l,l-trifluoro-2-alkanols have been the target of organic synthesis. Conventional retrosynthetic analysis of the trifluoro alcohols leads to (1) resolution of l,l,l-trifIuoro-2-alkanols by chemical or enzymatic methods, (2) asymmetric reduction of l,l,l-trifluoro-2-alkanones, or (3) asymmetric carbonyl addition of carbonaceous nucleophiles. Indeed, at present, the enzymatic resolution through the hydrolysis of the carboxylates of l,l,l-trifluoro-2-alkanols prevails. Other methods remain yet to be studied. 

The enzymatic reduction of a thiocarbonyl compound has been investigated [159] for the first time, in order to provide a new route for enan-tiopure thiols, molecules which are currently needed for asymmetric synthesis. Reaction of easily available /1-thioxoesters with baker s yeast under classical conditions did furnish the expected thiols, but with lower enantiomeric purity and moderate conversion rate, due to the competitive hydrolysis of the thioxo group into a carbonyl leading to an alcohol. However, conditions (ethyl acrylate, dry yeast) were found to improve the production of (S)-ethyl 3-mercaptobutanoate. Cyclic thioxo esters led to high stereoselectivity of cis (1S,2S) products, but with moderate chemical yields. 

In summary, a broad range of large-scale applicable biocatalytic methodologies have been developed for the production of L-amino acids in technical quantities. Among these industrially feasible routes, enzymatic resolutions play an important role. In particular, L-aminoacylases, L-amidases, L-hydantoinases in combination with L-carbamoylases, and /l-lactam hydrolases are efficient and technically suitable biocatalysts. In addition, attractive manufacturing processes for L-amino acids by means of asymmetric (bio-)catalytic routes has been realized. Successful examples are reductive amination, transamination, and addition of ammonia to rx,/fun-saturated carbonyl compounds, respectively. 

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