STEREOSELECTIVE BIOCATALYTIC FORMATION OF CYANOHYDRINS, VERSATILE BUILDING BLOCKS FOR ORGANIC SYNTHESIS

摘要

Cyanohydrins have been shown to be excellent chiral building blocks in organic synthesie. They are expedient starting materials for the preparation of several important classes of compounds such as α -hydroxy acids, acyloins, α -hydroxy aldehydes, vicinal diols, ethanolamines and α- and β -amino acids. This will be illustrated in the second part 2 of this chapter. During the past decades there has been an upsurge of interest in methods for the synthesis and application of chiral cyanohydrins in non-racemic form. It may be expected that in the near future these products will constitute an important addition to the range of commercially available chiral building blocks for the production of Pharmaceuticals, pesticides, vitamins, unusual amino acids and resolving agents. Cyanohydrins are usually prepared by the addition of hydrogen cyanide (HCN) to aldehydes and ketones or, indirectly, by the addition of trimethylsilyl cyanide followed by acid hydrolysis. When aldehydes or unsymmetrical ketones are used as substrates, a stereogenic center is created. Methods for the synthesis of chiral cyanohydrins in non-racemic form can be divided in chemical methods and enzymatic methods. In general the chemical approaches, using chiral catalysts, have the advantage that a broad range of aldehydes can be used. Up to now major disadvantages are the moderate enantiomeric excess (e.e.) and the problems encountered in separating the catalyst from the product. The two most important enzymatic approaches to chiral cyanohydrins are enzymatic kinetic resolution by lipases or esterases (whole cells or purified enzymes) and enzymatic asymmetric synthesis by R- or S-hydroxynitrile lyases (HNL's). Inherent disadvantages of kinetic resolution are the need of separating the hydrolyzed product from its ester and the maximum theoretical yield of only 50%. Biocatalysis using the R-HNL from almonds, and synthetic applications of chiral cyanohydrins have been thoroughly studied in our laboratories over the past decade.