Negishi Cross-Coupling Provides Alkylated Tryptophans and Tryptophan Regioisomers

Mild transition-metal catalysed cross-couplings enable direct functionalisation of biocatalytically halogenated tryptophans with alkyl iodides, representing a new alternative for late-stage derivatisations of halogenated aromatic amino acids. Moreover, this strategy enables preparation of (homo)tryptophan regioisomers in a simple two-step synthesis using a Pd-catalysed Negishi cross coupling. This method provides access to non-canonical constitutional surrogates of tryptophan, ready for use in peptide synthesis.

Automated summary

Mild transition-metal catalysed cross-couplings allow for direct functionalization of biocatalytically halogenated tryptophans and provide a simple way to synthesize (homo)tryptophan regioisomers. This method offers non-canonical constitutional surrogates of tryptophan for use in peptide synthesis.