Total Synthesis of Alloviroidin

Abstract

Alloviroidin is a cyclic heptapeptide, produced by several species of Amanita mushrooms, that demonstrates high affinity for F-actin as is characteristic of virotoxins and phallotoxins. Alloviroidin was synthesized via a [3 + 4] fragment condensation of Fmoc-d-Thr­(OTBS)-d-Ser­(OTBS)-(2S,3R,4R)-DHPro­(OTBS)2-OH and H-Ala-Trp­(2-SO2Me)-(2S,4S)-DHLeu­(5-OTBS)-Val-OMe to form bond A. The linear heptapeptide favored a turn conformation, facilitating cyclization between Val1 and d-Thr2 (position B). Global deprotection and HPLC purification afforded alloviroidin with NMR spectra in excellent agreement with the natural product.