A solid-phase approach to the phallotoxins: total synthesis of [Ala7]-phalloidin.
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.
Anderson
Marc O
MO
Department of Pharmaceutical Chemistry, University of California at San Francisco, California 94143-2280, USA.
Shelat
Anang A
AA
Guy
R Kiplin
RK
D000546:Amanitins / Q000138:chemical synthesis*; D002625:Chemistry, Organic / Q000379:methods; D015394:Molecular Structure; D010590:Phalloidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
C430290:Ala(7)-phalloidin; D000546:Amanitins; D010590:Phalloidine; C018358:phallotoxin