A1 Refereed original research article in a scientific journal
Solid-supported synthesis of bicyclic peptides containing three parallel peptide chains
Authors: Karskela T, Heinonen P, Virta P, Lonnberg H
Publisher: WILEY-V C H VERLAG GMBH
Publication year: 2003
Journal:: European Journal of Organic Chemistry
Journal name in source: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
Journal acronym: EUR J ORG CHEM
Issue: 9
First page : 1687
Last page: 1691
Number of pages: 5
ISSN: 1434-193X
DOI: https://doi.org/10.1002/ejoc.200210517
Abstract
Four homodetic bicyclic peptides 9a-d, containing three parallel peptide chains, were synthesized on a hydroxymethyl-functionalized polystyrene support. alpha,alpha-Bis(aminomethyl)-beta-alanine, bearing orthogonal protections (Alloc, Boc, Fmoc) on the three amino groups (1), was attached to the support through an H2N-Leu-Leu-Gly-OH spacer, and the peptide chains were assembled on the amino groups of 1 by either a stepwise coupling or coupling of a segment, keeping the amino protection within each chain unchanged. N-(4-Allyloxy-4-oxobutanoyl)iminodiacetic acid (2) was then coupled to the Fmoc-protected chain. The Boc protecting group was removed, and the exposed amino group was coupled with the remaining free carboxylic acid function of 2. Finally, the Alloc and allyl ester protections were removed from the carboxylic and amino functions, and a second cyclization was performed. Release from the support gave 9a-d as free carboxylic acids.
Four homodetic bicyclic peptides 9a-d, containing three parallel peptide chains, were synthesized on a hydroxymethyl-functionalized polystyrene support. alpha,alpha-Bis(aminomethyl)-beta-alanine, bearing orthogonal protections (Alloc, Boc, Fmoc) on the three amino groups (1), was attached to the support through an H2N-Leu-Leu-Gly-OH spacer, and the peptide chains were assembled on the amino groups of 1 by either a stepwise coupling or coupling of a segment, keeping the amino protection within each chain unchanged. N-(4-Allyloxy-4-oxobutanoyl)iminodiacetic acid (2) was then coupled to the Fmoc-protected chain. The Boc protecting group was removed, and the exposed amino group was coupled with the remaining free carboxylic acid function of 2. Finally, the Alloc and allyl ester protections were removed from the carboxylic and amino functions, and a second cyclization was performed. Release from the support gave 9a-d as free carboxylic acids.
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