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

Abstract

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.

Total Synthesis of (+)‐trans‐Trikentrin A

“…Biocatalysis has recently been used in various total syntheses of natural products 22a,b. The mild conditions usually required for enzymatic resolution, coupled with the high selectivity and substrate specificity of enzymes,22b,c make it a powerful tool in organic synthesis22b and in industry 22d.…”

Genome mining and characterisation of a novel transaminase with remote stereoselectivity

“…Hydrolases can be used to resolve remote stereocentres 35–37 , and have been particularly important biocatalysts in the context of resolution of APIs and pharmaceutical intermediates 33,34,39,60 . In some cases, more than one stereocentre can be resolved 38 .…”

“…Most biocatalytic transformations focus on enantioselection at or near to the site of reaction. There are some examples of biocatalytic resolution of remote stereogenic centres, for example using hydrolases 33–39 . In contrast, transaminase-mediated resolution of compounds bearing even a second stereocentre are very rare.…”

Production of Bulk Chemicals with Biocatalysis: Drivers and Challenges Reflected in Recent Industrial Granted Patents (2015–2020)

“…In recent decades, industrial processes using biocatalysts have boosted, with major applications devoted to the development of (highly valuable) pharmaceutical products [ 3 ]. This has been motivated by the advantageous properties of enzymes, such as enantio- [ 4 , 5 , 6 ], regio- [ 7 , 8 ] and chemo-selectivity [ 8 ], together with the fact that the high market value of the products makes the application of the biocatalysts profitable [ 9 ].…”