title: Efficient oxidation of N-protected tryptophan and tryptophanyl-dipeptides by in situ generated dimethyldioxirane provides hexahydropyrroloindoline-containing synthons suitable for peptide synthesis and subsequent tryptathionylation.
abstract: A series of hydroxypyrroloindoline (Hpi) containing dipeptides along with the corresponding monomeric Hpi-α-amino acid (Hpi-2-carboxylate), were prepared by reacting a series of Nα-protected-tryptophans in aqueous or biphasic [water/cyclopentyl methyl ether (CPME)] solutions containing Oxone®(potassium peroxymonosulfate) and acetone. This procedure avoids the tedious distillation of unstable dimethyldioxirane (DMDO), which is commonly used to oxidize indoles. Monomers Nα-Boc-Hpi-OH and Nα-Fmoc-Hpi-OH were readily incorporated by solid-phase peptide synthesis (SPPS) into a peptide containing a cysteine; in trifluoroacetic acid (TFA), the Hpi underwent intramolecular dehydrative condensation with the cysteine thiol to afford the anticipated tryptathionine crosslink. This eco- and user-friendly oxidative methodology greatly simplifies the synthesis of Hpi derivatives while enabling the synthesis of tryptathionine crosslinks characteristic of phalloidin and amanitin, two potent peptide toxins of present interest.
authors.affiliation: Department of Chemistry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Antoine
authors.initials: A
authors.lastname: Blanc
authors.affiliation: Department of Chemistry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Fan
authors.initials: F
authors.lastname: Xia
authors.affiliation: Department of Chemistry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Mihajlo
authors.initials: M
authors.lastname: Todorovic
authors.affiliation: Department of Chemistry, University of British Columbia, Vancouver, BC, Canada. dperrin@chem.ubc.ca.
authors.forename: David M
authors.initials: DM
authors.lastname: Perrin
mesh_terms: D060326:Chemistry Techniques, Synthetic; D003545:Cysteine / Q000737:chemistry; D004151:Dipeptides / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D014364:Tryptophan / Q000737:chemistry*
chemical_list: D004151:Dipeptides; D004852:Epoxy Compounds; D010455:Peptides; D014364:Tryptophan; D003545:Cysteine; C064455:dimethyldioxirane
keywords: 3a-Hydroxypyrrolo[2,3-b]indoline; Dimethyldioxirane; Peptide synthesis; Tryptophan oxidation