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Backbone Amide Linker Strategy for the Synthesis of 1,4‐Triazole‐Containing Cyclic Tetra‐ and Pentapeptides
Author(s) -
Springer Jasper,
de Cuba Kimberly R.,
CalvetVitale Sandrine,
Geenevasen Jan A. J.,
Hermkens Pedro H. H.,
Hiemstra Henk,
van Maarseveen Jan H.
Publication year - 2008
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200800143
Subject(s) - chemistry , linker , solid phase synthesis , combinatorial chemistry , amide , alkyne , cycloaddition , cyclic peptide , triazole , click chemistry , peptide synthesis , tetra , azide , moiety , stereochemistry , polymer chemistry , peptide , organic chemistry , medicinal chemistry , catalysis , biochemistry , computer science , operating system
A backbone amide linker strategy was chosen for the solid‐phase synthesis of triazole‐containing cyclic tetra‐ and pentapeptides. An alkyne‐substituted linker derived from 4‐hydroxy‐2‐methoxybenzaldehyde was elongated by using standard “Fmoc‐based” solid phase chemistry and terminated by coupling of an azido acid. In solution, the peptides were cyclized by a Cu I ‐catalyzed azide‐alkyne cycloaddition reaction. The solid‐supported synthesized linear peptides had to be cleaved prior to cyclization. As an example of cyclic tetrapeptides, a triazole analog of cyclo ‐[Pro‐Val‐Pro‐Tyr] ( 2 ) was prepared by the solid‐phase/solution‐phase method. For the cyclic pentapeptides, segetalin B ( 3 ) was chosen as a model compound to show the applicability of this method.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)