A solid-phase approach to the phallotoxins: total synthesis of [Ala7]-phalloidin

J Org Chem. 2005 Jun 10;70(12):4578-84. doi: 10.1021/jo0503153.


Herein we report a solid-phase synthetic approach to [Ala7]-phalloidin (1). Prior syntheses of phallotoxins were carried out using solution-phase routes that required large scale and preclude library production. The route presented here consists of solution-phase preparation of key orthogonally protected amino acid building blocks, followed by a solid-phase peptide synthesis sequence, featuring two resin-bound macro-cyclization reactions. The final product mixture was composed of two atropisomeric compounds, one designated "natural" (1) and the other designated "non-natural" (1'). The structures of these species were modeled using restrained energy minimization with NMR-derived restraints.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amanitins / chemical synthesis*
  • Chemistry, Organic / methods
  • Molecular Structure
  • Phalloidine / analogs & derivatives*
  • Phalloidine / chemical synthesis*


  • Ala(7)-phalloidin
  • Amanitins
  • Phalloidine
  • phallotoxin