Current Progress in the Chemoenzymatic Synthesis of Natural Products

Abstract

Natural products, with their array of structural complexity, diversity, and biological activity, have inspired generations of chemists and driven the advancement of techniques in their total syntheses. The field of natural product synthesis continuously evolves through the development of methodologies to improve stereoselectivity, yield, scalability, substrate scope, late-stage functionalization, and/or enable novel reactions. One of the more interesting and unique techniques to emerge in the last thirty years is the use of chemoenzymatic reactions in the synthesis of natural products. This review highlights some of the recent examples and progress in the chemoenzymatic synthesis of natural products from 2019–2022.

Controllable skeletal reorganizations in natural product synthesis

“…Chemoenzymatic approaches that combine chemical transformations with enzymatic oxidation appear to be an attractive solution to this challenge, owing to the boom in research on enzyme engineering. [186][187][188][189][190][191][192] Moreover, integration of functionalization and rearrangement processes into a single transformation can result in synthetic routes that are much more concise and direct. The thriving eld of transition-metal catalysis is sure to facilitate such integration because transition-metal catalysts can activate C-H and C-C bonds that are traditionally considered to be inert and can also mediate various C-C bond forming reactions.…”

Directed Evolution of a Modular Polyketide Synthase Thioesterase for Generation of a Hybrid Macrocyclic Ring System

“…2,14,[21][22][23][24][25] Chemoenzymatic synthesis encompasses assembly of intermediates from simple building blocks, combined with enzyme catalyzed reactions to obtain efficient production of novel molecules and pharmaceuticals using aqueous reaction conditions, while avoiding toxic reagents, solvents and protecting groups. [26][27][28][29][30][31] Although workable synthetic methodologies exist for macrolactonization, these are often met with unfavorable entropic and enthalpic factors relating to the energetics of intramolecular cyclization. [15][16][17]32 To address the challenges of total and semi-synthesis, we have been investigating the pikromycin (Pik) biosynthetic pathway thioesterase (TE) domain as a key biocatalyst for macrolide antibiotic discovery.…”

Dual-Mode Ce-MOF Nanozymes for Rapid and Selective Detection of Hydrogen Sulfide in Aquatic Products

“…However, natural peroxidases exhibit high catalytic activity but are susceptible to environmental conditions such as pH and temperature, which can lead to decreased activity or complete inactivation [ 12 ]. Consequently, natural peroxidases are impractical for use outside laboratory settings.…”