A Photoenzyme for Challenging Lactam Radical Cyclizations

Bryce T. Nicholls, Tianzhang Qiao, Todd K. Hyster

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Reductive radical cyclizations are ubiquitous in organic synthesis and have been applied to the synthesis of structurally complex molecules. N-Heterocyclic motifs can be prepared through the cyclization of α-haloamides; however, slow rotation around the amide C N bond results in preferential formation of an acyclic hydrodehalogenated product. Here, we compare four different methods for preparing γ-, δ-, ϵ-, and ζ-lactams via radical cyclization. We found that a photoenzymatic method using flavin-dependent 'ene' reductases affords the highest level of product selectivity. We suggest that through selective binding of the cis-amide isomer, the enzyme preorganizes the substrate for cyclization, helping to avoid premature radical termination.

Original languageEnglish (US)
Pages (from-to)1204-1208
Number of pages5
Issue number12
StatePublished - Jul 1 2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Organic Chemistry


  • biocatalysis
  • lactam synthesis
  • radical chemistry


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