Biocatalyzed Regio- and Chemoselective Ester Cleavage: Synthesis of Bioactive Molecules

• Published in: ChemCatChem Vol. 4; no. 5; pp. 592 - 608
• Main Authors: Barbayianni, Efrosini, Kokotos, George
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.05.2012; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: bioactive molecules; biocatalysis; chemoselectivity; ester cleavage; regioselectivity
• ISSN: 1867-3880; 1867-3899
• DOI: 10.1002/cctc.201200035

Biocatalysis is one of the greenest technologies for the synthesis of bioactive molecules, for which the presence of various functional groups requires selective protection or deprotection processes. The effective combination of protecting group techniques often results in additional chemical synthetic steps. At this point, enzymes can prove very valuable, as they help to circumvent several reaction steps, owing to the selectivity they show for a particular group. Specifically, carboxylic acid and alcohol functionalities, as well as esters, are of high importance for the biological properties of certain molecules. Esters are enzyme‐labile moieties, a characteristic that many drugs activity is based on. Ester cleavage is also required for synthesis, where beyond any doubt, the majority of reactions and conditions must be highly selective. This review aims to highlight a number of examples in the literature relative to regio‐ and chemoselective biocatalytic deprotection processes of the carboxyl and hydroxyl moieties, used in the synthesis of pharmaceuticals, bioactive molecules, and drug precursors. A matter of choice: Biocatalysts are versatile tools in organic synthesis for regio‐ and chemoselective transformations. Particularly lipases and esterases can preferentially cleave carboxylic esters, depending on their nature or their position on a complex molecule. This review aims to highlight selected examples, where biocatalysis has been used for the regio‐ and chemoselective cleavage of carboxylic esters in various categories of structurally different bioactive natural products and synthetic molecules.