Biocatalyst organic synthesis

It is apparent that the use of enzymatic catalysis continues to grow Greater availabiUty of enzymes, development of new methodologies for thek utilization, investigation of enzymatic behavior in nonconventional environments, and the design and synthesis of new biocatalysts with altered selectivity and increased stabiUty are essential for the successhil development of this field. As more is learned about selectivity of enzymes toward unnatural substrates, the choice of an enzyme for a particular transformation will become easier to predict. It should simplify a search for an appropriate catalyst and help to estabhsh biocatalytic procedures as a usehil supplement to classical organic synthesis. 

In contrast to the above two examples, for which applications were developed long before the responsible biocatalyst was discovered, aldolase applications are more recently developed. Indeed, aldolases and their natural function were extensively studied between the end of the 1960s and the beginning of the 1970s. The first patents about their applications in organic synthesis appear in the 1990s [67-69] and the first ton-scale applications were reported in 1997... 

The production of optically active cyanohydrins, with nitrile and alcohol functional groups that can each be readily derivatized, is an increasingly significant organic synthesis method. Hydroxynitrile lyase (HNL) enzymes have been shown to be very effective biocatalysts for the formation of these compounds from a variety of aldehyde and aliphatic ketone starting materials.Recent work has also expanded the application of HNLs to the asymmetric production of cyanohydrins from aromatic ketones. In particular, commercially available preparations of these enzymes have been utilized for high ee (5)-cyanohydrin synthesis from phenylacetones with a variety of different aromatic substitutions (Figure 8.1). 

The reasons for the increasing acceptance of enzymes as reagents rest on the advantages gained from utilizing them in organic synthesis Isolated or wholecell enzymes are efficient catalysts under mild conditions. Since enzymes are chiral materials, optically active molecules may be produced from prochiral or racemic substrates by catalytic asymmetric induction or kinetic resolution. Moreover, these biocatalysts may perform transformations, which are difficult to emulate by transition-metal catalysts, and they are environmentally more acceptable than metal complexes. 

Oxidoreductases are, after lipases, the second most-used kinds of biocatalysts in organic synthesis. Two main processes have been reported using this type of enzymes-bioreduction of carbonyl groups [39] and biohydroxylation of non-activated substrates [40]. However, in recent few years other processes such as deracemization of amines or alcohols [41] and enzymatic Baeyer-Villiger reactions of ketones and aldehydes [42] are being used with great utility in asymmetric synthesis. 

Gotfredsen, S.E., Ingvorsen, K., Yale, B. and Andersen, O. (1985) The scope of biocatalysts in organic chemical processing. In Biocatalysts in Organic Synthesis, edited by J.Tramper, H.C.van der Plas and P.Linko, pp. 3-18. Amsterdam Elsevier. 

Plas u. E. Linko, Biocatalysts in Organic Synthesis, S. 135, Elsevier Publ. Amsterdam 1985. 

Woodley JM (1992) Immobilized Biocatalysts. In Smith K (ed) Solids Supports and Catalysts in Organic Synthesis. Ellis Horwood, Chichester, p 254... 

In general there are two principle possibilities using a biocatalyst in organic synthesis, namely as whole cells or as isolated enzymes - free or immobilized. The advantages and disadvantages of each can be intensively discussed, but the outcome of this consideration always depends on the whole system and the kind of application. There are numerous examples of both and thus there is no partitioning between whole cell biotransformation and isolated enzymes in this review. 

Kinetic resolutions in general are regularly applied in organic synthesis. Since enzymes are highly attractive for asymmetric synthesis, various types of biocatalysts have been used in enzymatic (dynamic) kinetic resolutions, but the focus will remain on lipase- and esterase-mediated resolutions as the most common tools in early steps of natural product syntheses. 

In current research, oxidoreductases are second in the number of applications of enzymes in organic synthesis. The number of commercially available biocatalysts of this class has increased tremendously during the last few years and various screening kits for oxidation and reduction are sold. Many oxidoreductases are rather easy to handle, though, in contrast to hydrolases, they are dependent on cofactors [22]. 

Fonseca AM, Monte FJQ et al (2009) Coconut water (Cocos nucifera L.) - a new biocatalyst system for organic synthesis. J Mol Catal B Enzym 57 78-82... 

Biocatalysts, mainly hydrolytic enzymes and oxidoreductases, have been used for organic reactions due to their excellent enantioselectivities and environmentally friendliness.1 Typical enzymatic reactions used for the organic synthesis are shown in Figure 1. Especially, hydrolytic enzymes for kinetic resolutions of racemates have been utilized widely because of their high stabilities, wide substrate specificities, lack of cofactor requirements and high availabilities. 

---