Enzyme-catalyzed aldol addition aldolases application

Asymmetric C-C bond formation is the most important and most challenging problem in synthetic organic chemistry. In Nature, such reactions are facilitated by lyases, which catalyze the addition of carbonucleophiles to C=0 double bonds in a manner that is classified mechanistically as an aldol addition [1]. Most enzymes that have been investigated lately for synthetic applications include aldolases from carbohydrate, amino acid, or sialic acid metabolism [1, 2]. Because enzymes are active on unprotected substrates under very mild conditions and with high chemo-, regio-, and stereoselectivity, aldolases and related enzymes hold particularly high potential for the synthesis of polyfunctionalized products that are otherwise difficult to prepare and to handle by conventional chemical methods. 

An asymmetric C-C coupling, one of the most important and challenging problems in synthetic organic chemistry, seems to be most appropriate for the creation of a complete set of diastereomers because of the applicability of a convergent, combinatorial strategy [38-40]. In Nature, such reactions are facilitated by lyases which catalyze the (usually reversible) addition of carbo-nucleophiles to C=0 double bonds, in a manner mechanistically most often categorized as aldol and Claisen additions or acyloin reactions [41], The most frequent reaction type is the aldol reaction, and some 30 lyases of the aldol type ( aldolases ) have been identified so far [42], of which the majority are involved in carbohydrate, amino acid, or hydroxy acid metabolism. This review will focus on the current state of development of this type of enzyme and will outline the scope and limitations for their preparative application in asymmetric synthesis. 

Aldolases are a group of C—C bond forming enzymes with widespread applications. The stereoselective aldol addition reaction catalyzed by aldolases represents an attractive alternative to conventional chiral organic chemistry methods for chemical and pharmaceutical industries. Aldolases are classified according to both their proposed catalytic mechanism and the structure of the donor substrate, their sources and microbial production processes being presented in this chapter. To design appropriate bioreactors for aldol synthesis, the characteristics of aldolase biocatalysts obtained after purification procedures in free and immobilized form are discussed. 

Finally, several other animal tissues yield useful enzymes that have been employed in S5mthesis. Pepsin is an important digestive protease from animal stomach whose native role is hydrolyzing amide bonds involving hydrophobic, aromatic amino adds, for example, phenylalanine, tyrosine, and tryptophan. Acylase from pordne kidney sdectivdy hydrolyzes N-acetyl amino adds and is commercially available. It has long been used for kinetic resolutions of amino adds. In addition to hydrolases, other animal enzymes have found important applications in biocatalysis. Rabbit musde aldolase is commerdally awiilable and was shown to catalyze aldol condensations between dihydroxyacetone phosphate and various nonnatural aldehydes by the Whitesides group in 1989 [10]. This seminal report touched off an avalanche of new applications for this and related enzymes in asymmetric synthesis. 

---