Research & Faculty

Default Header Image

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

TitleHigh 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
Publication TypeJournal Article
Year of Publication2005
AuthorsMay, JP, Fournier, P, Pellicelli, J, Patrick, BO, Perrin, DM
JournalJournal of Organic Chemistry
Volume70
Pagination8424-8430
Date PublishedOct
Type of ArticleArticle
ISBN Number0022-3263
KeywordsANALOGS, ASYMMETRIC EPOXIDATION METHOD, CONFIGURATION, CONFORMATION, CYCLIZATION, CYSTEINE SULFHYDRYL-GROUPS, DERIVATIVES, HIMASTATIN, OXYGENATION, TRYPTOPHAN
Abstract

This work describes a rapid and high yielding oxidation of 14 tryptophanylated amino acid methyl esters to the corresponding 3 alpha-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 H-1 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.

URL<Go to ISI>://000232405500022