Enantioselective Enzymatic Desymmetrizations in Organic Synthesis

During the recent past years, tremendous efforts have been made to establish enantioselective routes for the preparation of enantiomerically pure compounds due to their importance in the pharmaceutical, agricultural, and food industries. This is reflected in the fact that the sales of single-enantiomer small-molecule drugs has reached c. US 10 billion in 2002. 1 Moreover, the FDA has become increasingly reluctant to permit the introduction of additional racemic drugs, as these therapies are by definition saddled with 50% of chemical ballast. 2 Enzymes are nowadays widely recognized among the most active and selective catalysts for the preparation of optically active compounds. 3 Some of the factors that account for this popularity are (1) They are chemo-, regio-, and stereoselective, and environmentally friendly. (2) Because of the mild conditions under which they operate, enzymatic reactions are affected to a lesser extent by side reactions (viz. isomerization, racemization, epimerization, and rearrangement of molecules) as compared to nonenzymatic processes. Nevertheless, organic chemists have been traditionally reluctant to employ biocatalysts in their syntheses. This is mainly because, in their natural form, most of the enzymes are very sensitive catalysts that exert their activity mainly in aqueous solution. Moreover, their handling requires some biochemistry knowledge. However, some recent advances carried out in the biocatalysis field have “approached” enzymes to organic synthesis: (a) They can operate in nonaqueous media accepting a broad range of substrates;4 (b) immobilization techniques increase their stability and simplify their handling. 5 Thus, many enzymes can now be acquired and used as any other chemical.