New Biocatalysts via Chemical

But there is still another point, not yet discussed but with considerable potential, which may also impact eventually on technical asymmetric catalysis. Even though biocatalysts are efficient, active, and selective, there still remains one big disadvantage At present, there is not yet an appropriate enzyme known or available for every given chemical reaction. It is estimated that about 25 000 enzymes exist in Nature, and 90% of these have still to be discovered [28, 29]. New biocatalysts are made available nowadays not only from screening known organism but also via screening metagenomic libraries and directed evolution techniques [30]. 

Although biocatalysis is the new kid on the block, more and more companies are using enzymes for chemical manufacture. One reason for this is that biocatalysts give sustainable alternatives to chemical manufacture, and not just for making chiral products. The synthesis of acrylamide via an enzyme-catalyzed water addition to acrylonitrile (2-propenenitrile) is a classic example (Figure 1.15). It uses the Rhodo-coccus enzyme nitrile hydratase. Commercialized in 1985 by Nitto Chemicals in... 

Recent employment of optically active fluorinated compounds for biologically active substances (7-2) or ferroelectric liquid crystals (3-5) has emphasized the versatility of these chiral molecules, while few methods have been reported for the preparation of such materials in a highly diastereo- as well as enantioselective manner. On the other hand, recent investigations in this field have opened the possibility for the introduction of chirality via asymmetric reduction or optical resolution by employing biocatalysts such as baker s yeast (6-75) or hydrolytic enzymes (16-20), respectively (27-23), along with the conventional chemical methodology (24-27). Chiral materials thus obtained may also be utilized in diastereoselective reactions which create new chiral centers (77). In this paper, the authors would like to discuss our recent progress in the preparation of optically active fluorinated compoounds and the effect of fluorine atom(s) on the reactivity and selectivity. 

From an extensive screening of microorganisms, we first developed such a biocatalyst, Alcallgenes bronchlsepticus, in 1989 [Eq. (11)] [12]. (/ )-Phenylpropionic acid (21a) was obtained from a-methyl-a-phenylmaloiiic acid (22a), and the yield and e.e. of the products were exteemely high. Indeed, this is a new type of biotransformation that can be performed on a preparative scale since the substrates, disubstituted malonates, are readily available via the well-established malonate ester synthesis. To date, all of the attempts for enantioselective decarboxylation of malonates by a chemical asymmetric synthesis resulted in only low to moderate e.e. of the products. In order to understand the mechanism of this enzyme-mediated decarboxylation we embarked on the isolation of the enzyme and further study of its characteristics. 

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