Work

Computational Prediction and Experimental Validation of a Bridged Cation Intermediate in Akanthomycin Biosynthesis

Year: 2022

Type: article

Abstract: Here we report a computation-driven chemoenzymatic synthesis and biosynthesis of the natural product deoxyakanthomycin, an atropisomeric pyridone natural product that features a 7-membered carbocycle with five stereocenters, one of which a quaternary center. The one-step synthesis from a biosynthetic precursor is based on computational analysis that predicted a σ-bridged cation mediated cyclization mechanism to form deoxyakanthomycin. The σ-bridged cation rationalizes the observed substrate-controlled selectivity; diastereoselectivity arises from attack of water anti to the σ-bridging, as is generally found for σ-bridged cations. Our studies also reveal a unifying biosynthetic strategy for 2-pyridone natural products that derive from a common o -quinone methide to create diverse structures.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.2c02288

Authors: Cooper S. Jamieson, Masao Ohashi, K. N. Houk, Yi Tang

Institution: University of California, Los Angeles

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funder: National Institute of Allergy and Infectious Diseases

Awards: G2717461293, G8627431479