Work

Enantioselective Total Synthesis of Two Aromatized Halicyclamines

Year: 2026

Type: article

Abstract: The concise and divergent syntheses of the marine alkaloids (+)-tetradehydrohalicyclamine B and (–)-epi-tetradehydrohalicyclamine B are disclosed. Each synthesis requires ten steps and hinge on several key transformations includ-ing an enantioselective organocatalyzed Michael addition, a macrocyclic aza-Wittig ligation, and reagent-controlled stereodi-vergent lactam reductions to assemble their core molecular frameworks. This approach constitutes the first reported asymmet-ric syntheses of these natural products, while importantly enabling the controlled assembly of the trans stereochemical rela-tionship adorning the piperidine ring, a relative configuration that was previously inaccessible. The careful employment of highly oxidized starting materials served as an underpinning of this synthetic strategy, streamlining fragment assembly and alleviating the need for circuitous functional group interconversions or extraneous redox.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.5c22699

Authors: Zackary D. Firestone, Thiago A. Grigolo, Filipe G. Pernichelle, Joel M. Smith

Institution: Florida State University

Language: English

Topic: Advanced Synthetic Organic Chemistry

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Science Foundation, National Institutes of Health

Awards: Dearomative Alkaloid Synthesis, G9000054327, Scalable Synthesis and New Bond Disconnections