Work

On the Abundance and Stability of Diazo-Containing Secondary Metabolites: Enantioselective Synthesis of (−)-Nenestatin A

Year: 2023

Type: article

Abstract: Here, we report an enantioselective synthesis of the monomeric nes product (−)-nenestatin A, via the intermediary diazofluorene “diazonenestatin A.” Our route features a convergent, aldol-based fragment coupling to assemble the carbon skeleton and a diazotransfer to a highly conjugated tetracyclic fulvene. We find that diazonenestatin A is transformed to nenestatin A under conditions that mimic the bacterial fermentation, suggesting that the nes pathway may produce unstable diazofluorene products that have eluded isolation.

Source: Organic Letters

DOI: 10.1021/acs.orglett.3c01175

Authors: Madeline C. Frischling, Seth B. Herzon

Institution: Yale University

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology (medical)

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences, National Center for Advancing Translational Sciences

Awards: G1691437995, Synthetic and translational studies of antitumor and antimicrobial natural products., Yale Clinical and Translational Science Award