Solid-supported synthesis of bicyclic peptides containing three parallel peptide chains



: Karskela T, Heinonen P, Virta P, Lonnberg H

Publisher: WILEY-V C H VERLAG GMBH

: 2003

: European Journal of Organic Chemistry

: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY

: EUR J ORG CHEM

: 9

: 1687

: 1691

: 5

: 1434-193X

DOI: https://doi.org/10.1002/ejoc.200210517


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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