Enantioselectve enzymatic desymmetrization catalyzed in the presence of lipase. Part 1, Prochiral compounds

In the enzymatic asymmetric synthesis, the enzyme allows the desymmetrization of achiral compounds resulting in chiral compounds of high optical purity. Therefore, this type of biotransformation is known as enantioselective enzymatic desymmetrization (EED) [1–11]. This method is related to the generation of an asymmetry (loss of symmetry elements) in prochiral molecules (most often an sp3 or sp2 hybridized carbon atom), in meso synthones, and centrosymmetric compounds. An achiral center of the tetrahedral system is defined as a prochiral one if it becomes chiral as a result of one of the two substituents replacement which, when separated from the particles, are indistinguishable (Scheme 1, 2) [1–4, 9, 12]. Asymmetric synthesis is enantioselective when one of the enantiotopic groups or faces of an optically inactive compound is biotransformed faster than the other (Scheme 3–5) [1, 10, 11, 13–15]. Lipases are enzymes of highest importance in stereoselective organic synthesis, mainly due to their exceptionally broad substrate tolerance, stability, activity in unphysiological systems, and relatively low price [9, 14]. The mechanism of enzymatic hydrolysis catalysed by hydrolases is similar to that observed in the chemical hydrolysis with the use of base. The selectivity of enzymatic catalysis depends on the substrate orientation in the enzyme active site (Scheme 6, 7) [25–29]. Lipases were successfully used for the desymmetrization of different prochiral diesters, alcohols and amines. Most lipases preferentially convert the same prochiral groups in the above mentioned types of reaction. This allows the preparation of the both enantiomers of the product in high chemical and optical yield (Scheme 9–13) [9, 13, 32–56]