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Intraannular Savige-Fontana reaction: One-step conversion of one class of monocyclic peptides into another class of bicyclic peptides

TitleIntraannular Savige-Fontana reaction: One-step conversion of one class of monocyclic peptides into another class of bicyclic peptides
Publication TypeJournal Article
Year of Publication2008
AuthorsMay, JP, Perrin, DM
JournalChemistry-a European Journal
Volume14
Pagination3404-3409
Type of ArticleArticle
ISBN Number0947-6539
Keywords2-CHLOROTRITYL CHLORIDE, 2-THIOETHER DERIVATIVES, amatoxin, ANALOGS, CROSS-LINKING, CYSTEINE SULFHYDRYL-GROUPS, ILE3-AMANINAMIDE, indole, ISOPHAKELLISTATIN-3, natural products, OXIDATION, PEPTIDES, PHALLOTOXINS, RNA POLYMERASE-II, TRYPTOPHAN
Abstract

Cyclisation and cross-linking strategies are important for the synthesis of cyclic and bicyclic peptides. These macrolactams are of great interest due to their increased biological activity compared to linear analogues. Herein, we describe the synthesis of a cyclic peptide containing an Hpi toxicophore, reminiscent of phakellistatins and omphalotins. The first intraannular cross-linking of such a peptide is then presented: using neat TFA to catalyse a Savige-Fontana tryptathionylation, the Hpi-containing peptide is converted to a bicyclic amatoxin analogue. As such, this methodology represents an efficient cyclisation method for cross-linking peptides and exposes a heretofore unrealised relationship between two different classes of peptide natural products. This finding increases the degree of potential chemical space for library generation.

URL<Go to ISI>://000255230200019