Biocatalytic hydrogen atom transfer: an invigorating approach to free-radical reactions

Abstract

Initiating and terminating free-radical reactions via hydrogen atom transfer (HAT) is an attractive means of avoiding substrate prefunctionalization. Small molecule catalysts and reagents, however, struggle to execute this fundamental step with useful levels of diastereo- and enantioselectivity. In contrast, nature often carries out HAT with exquisite levels of selectivity for even electronically unactivated carbon–hydrogen bonds. By understanding how enzymes exploit and control this fundamental step, new strategies can be developed to address several long-standing challenges in free-radical reactions. This review will cover recent discoveries in biocatalysis that exploit a HAT mechanism to either initiate or terminate novel one-electron reactions.

Mimicry of a Non-ribosomally Produced Antimicrobial, Brevicidine, by Ribosomal Synthesis and Post-translational Modification

“…However, D-amino acids have been shown to play an important role on the antibacterial activity and the stability of some NRPs (Guo et al, 2018;Monaim et al, 2018). Peptide epimerases form a class of enzymes that can change L-amino acid residues to D-amino acid residues, including YydG, OspD, and PoyD (Fuchs et al, 2016;Nakano et al, 2019;Parent et al, 2018). Recently, substantial progress has been made in the study of peptide epimerases (Benjdia et al, 2017;Morinaka et al, 2017;Ogasawara, 2019;Vagstad et al, 2019).…”

Cooperative Hydrogen Atom Transfer: From Theory to Applications

“…The movement of one hydrogen atom and one electron concurrently from one orbital to another, or hydrogen atom transfer (HAT), is a fundamental reaction in the reactivity of organic molecules. [1][2][3][4][5][6][7][8] From the oxidation of biomolecules by cytochrome P450 enzymes 9 to an impressive array of earth abundant metal catalyzed reductive hydrofunctionalization reactions, 1,8 this elementary step is ubiquitous and essential to achieve otherwise challenging transformations. Despite these disparate applications, HAT reactions are all underpinned by the same general reactivity principles.…”

Photoenzymatic Generation of Unstabilized Alkyl Radicals: An Asymmetric Reductive Cyclization

“…Notable is the conserved tyrosine mutation as wild type GluER afforded product in lower yield and enantioselectivity (Table 1, entry 5), consistent with results from our previous hydrodehalogenation. 8 Moreover, oxygen provided to be detrimental to the reaction, with degassed reactions providing product in improved yields (Table 1, entry 6). 20 Finally, cooling the reaction from room temperature to 12 °C significantly improved reproducibility and provided a slight increase in yield (Table 1, entry 7).…”