P450-Mediated Coupling of Indole Fragments To Forge Communesin and Unnatural Isomers
Year: 2016
Type: article
Abstract: Dimeric indole alkaloids are structurally diverse natural products that have attracted significant attention from the synthetic and biosynthetic communities. Here, we describe the characterization of a P450 monooxygenase CnsC from Penicillium that catalyzes the heterodimeric coupling between two different indole moieties, tryptamine and aurantioclavine, to construct vicinal quaternary stereocenters and yield the heptacyclic communesin scaffold. We show, via biochemical characterization, substrate analogues, and computational methods that CnsC catalyzes the C3-C3' carbon-carbon bond formation and controls the regioselectivities of the pair of subsequent aminal bond formations to yield the communesin core. Use of ω-N-methyltryptamine and tryptophol in place of tryptamine led to the enzymatic synthesis of isocommunesin compounds, which have not been isolated to date.
DOI: 10.1021/jacs.6b01413
Authors: Hsiao-Ching Lin, Travis C. McMahon, Ashay Patel, Michael Corsello, Adam Simon, Wei Xu, Muxun Zhao, K. N. Houk, Neil K. Garg, Yi Tang
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Science Council, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Division of Graduate Education, National Center for Research Resources, National Center for Chronic Disease Prevention and Health Promotion, Division of Chemistry
OpenAlex ID: W2293215598