Enzyme-Catalysed Aldol Addition

Enzymes — in particular aldolases — are not only a supplement to classical methodologies, but also useful tools in many fields of aldol additions where classical synthetic procedures fail. This is the area of the synthesis of amino acids^1,2 and carbo-hydrates.^3,4,5,6,7,8 in the traditional sense. But more and more aldolases are used in C—C bond formation processes. Examples in natural product synthesis are given in Schetter and Mahrwald.⁹ Moreover, the combination of these two different synthetic strategies — the enzymatic route and the classical organic synthetic route — represent a valuable tool for the construction of defined stereogenic centres of natural products.¹⁰

Natural occurring aldolases are classified by their mode of action into two main groups: class I and class II aldolases. The accepted reaction mechanism of these two groups is shown below. Class I aldolases bind substrates via imine-enamine formation with a lysine residue of the active site of the enzyme. This step initiates the C—C bond formation process with an aldehyde and subsequent hydrolysis sets the aldol adduct free (Scheme 3.6.1).