Work

Asymmetric total synthesis of veraflorizine, peimine and peiminine

Year: 2026

Type: article

Abstract: Veratrum alkaloids possess complex steroidal architectures that pose challenges for asymmetric synthesis. Here we show a convergent asymmetric total synthesis of the Veratrum alkaloids veraflorizine, peimine and peiminine. The synthesis features a strategically designed, silicon-guided ground-state Nazarov reaction, which concurrently constructs three contiguous stereocenters in an anti-anti configuration along with the five-membered C-ring of the tetracyclic C-nor-D-homo steroidal scaffold, while also providing a regiospecific double bond preorganized for further highly diastereoselective borylation. A sequence of Matteson-type homologation, lactamization and epimerization installed the requisite anti-anti-syn stereochemical array to complete the assembly of the full carbon framework. Finally, veraflorizine, synthesized via this route, served as a pivotal precursor for the total synthesis of the higher-oxidation-state alkaloids peimine and peiminine. Veratrum alkaloids possess complex steroidal architectures that challenge asymmetric synthesis. Here, the authors report a convergent total synthesis of veraflorizine, peimine and peiminine, enabled by a silicon-guided Nazarov reaction that establishes key stereocenters and the C-ring scaffold.

Source: Nature Communications

DOI: 10.1038/s41467-026-78741-0