Solid-Phase Synthesis of Glu⁷-Phalloidin

Significance

An efficient solid-phase synthesis of Glu⁷-phalloidin (4) was reported. Thus, polystyrene-supported protected glutamic acid 1 was converted into the resin-bound heptapeptide 2 by using the standard Fmoc chemistry. After removal of the C-terminal allyl group and the N-terminal Fmoc group of 2, diphenylphosphorylazide (DPPA)-mediated cyclization afforded the resin-bound cyclic peptide 3 without formation of a cyclo­dimer or higher oligomers. The intramolecular thioether formation, followed by the removal of the polymer support and the protective groups, provided Glu⁷-phalloidin 4 in 50% overall yield based on the initial resin loading.