Solid-Phase-Based Synthesis of Lactazole-Like Thiopeptides

A strategy for the synthesis of de novo discovered lactazole-like thiopeptides is reported. The approach revolves around a convergent and scalable preparation of the central triheterocyclic amino acid and its utilization in Fmoc solid-phase peptide synthesis for modular peptide chain assembly. A technique for preparing C-terminally functionalized thiopeptides for biological studies is also described. The syntheses of 11 TNIK-inhibitor thiopeptides and 6 of their derivatives in multimilligram quantities highlight the practical utility of the developed protocols.

Automated summary

This article presents a strategy for synthesizing novel lactazole-like thiopeptides, including the preparation of central triheterocyclic amino acid and its use in solid-phase peptide synthesis, as well as a technique for preparing C-terminally functionalized thiopeptides for biological studies. The synthesis of 11 TNIK-inhibitor thiopeptides and 6 derivatives highlights the practicality of the developed protocols.