Enzyme‐Catalyzed StereoselectiveCCbond Formation Reactions in Total Syntheses

Abstract

The asymmetric formation of CC bonds is often a key step in the synthesis of biologically active (natural) products. As nature synthesizes many of these compounds with exquisite selectivity, it is not surprising that a rich toolbox of catalysts, enzymes, for the synthesis of CC bonds can be isolated from nature. The enantioselective formation of CC bonds is in particular catalyzed by the enzyme class of lyases but also by some transferases. Some of these enzymes, as hydroxynitrile lyases, benzaldehyde lyases, transketolases, aldolases, or decarboxylases, have been broadly used by organic chemists as efficient and versatile tools for asymmetric syntheses. Moreover, recent progress in molecular biology tools and protein engineering allows for improving their potential significantly.

The metal cofactor: stationary or mobile?

“…In addition to the movement of M-2, it was proposed that a water molecule acts catalytically as proton donor and that the hydroxy group at C-5 bears a negative charge after ring opening of the sugar (Kovalevsky et al 2010) ◂ molecule, here DHAP. In the vast majority of the cases, the metal is Zn(II) (Blom et al 1996;Brovetto et al 2011;Clapés 2015;Hanefeld et al 2022;Hélaine et al 2022;Ranoux 2013;Sukumaran and Hanefeld 2005).…”