Synthesis of Orthogonally Protected Labionin

We report the first synthesis of the complex amino acid labionin in a fully orthogonally protected and stereopure form. The structure-which incorporates five orthogonal protecting groups and three stereogenic centers-was assembled using two key synthetic steps: (1) a thia-Michael addition for installing the thioether bridge; (2) an electrophilic azidation for creating the central quaternary alpha-amino acid carbon in a stereochemically pure form. This work is expected to enable the solid phase synthesis of both natural and synthetic analogues labyrinthopeptins.

Automated summary

This work reports the first synthesis of the complex amino acid labionin in a fully orthogonally protected and stereopure form. The structure incorporates five orthogonal protecting groups and three stereogenic centers, assembled using thia-Michael addition and electrophilic azidation. The successful synthesis is expected to enable the solid phase synthesis of both natural and synthetic analogues of labyrinthopeptins.