title: High yielding synthesis of 3a-hydroxypyrrolo[2,3-b]indoline dipeptide methyl esters: synthons for expedient introduction of the hydroxypyrroloindoline moiety into larger peptide-based natural products and for the creation of tryptathionine bridges.
abstract: This work describes a rapid and high yielding oxidation of 14 tryptophanylated amino acid methyl esters to the corresponding 3a-hydroxypyrrolo[2,3-b]indoline (Hpi) amino acids with generally facile separation of syn-cis and anti-cis diastereomers. Structural X-ray diffraction data are presented for both diastereomers of Tr-Hpi-Gly-OMe, which allow for a putative assignment of the other 13 pairs of diastereomers reported herein, based on correlations with 1H NMR chemical shifts. Selective and high yielding deprotection at either the N or C terminus is described, allowing the Hpi motif to be introduced efficiently into potential targets with minimal protecting group manipulation. Two tripeptides containing Hpi and cysteine were prepared and treated with acid in the Savige-Fontana reaction to produce a cyclic tryptathionine linkage, characteristic of both amatoxins and phallotoxins.
authors.affiliation: Department of Chemistry, University of British Columbia, Vancouver, B.C. V6T 1Z1, Canada.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: May
authors.forename: Pierre
authors.initials: P
authors.lastname: Fournier
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pellicelli
authors.forename: Brian O
authors.initials: BO
authors.lastname: Patrick
authors.forename: David M
authors.initials: DM
authors.lastname: Perrin
mesh_terms: D003500:Cyclization; D003545:Cysteine / Q000737:chemistry; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D004952:Esters / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D008745:Methylation; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D014364:Tryptophan / Q000737:chemistry
chemical_list: D004151:Dipeptides; D004952:Esters; D007211:Indoles; D010456:Peptides, Cyclic; D011759:Pyrrolidines; D014364:Tryptophan; D003545:Cysteine