A1 Refereed original research article in a scientific journal
Orthogonally protected cyclo-beta-tetrapeptides as solid-supported scaffolds for the synthesis of glycoclusters
Authors: Virta P, Karskela M, Lonnberg H
Publisher: AMER CHEMICAL SOC
Publication year: 2006
Journal:: Journal of Organic Chemistry
Journal name in source: JOURNAL OF ORGANIC CHEMISTRY
Journal acronym: J ORG CHEM
Volume: 71
Issue: 5
First page : 1989
Last page: 1999
Number of pages: 11
ISSN: 0022-3263
DOI: https://doi.org/10.1021/jo052348o
Abstract
Two novel peptide scaffolds, viz. cyclo[(N-alpha-Alloc)Dpr-beta-Ala-(N-alpha-Fmoc)Dpr-beta-Ala] (1) and cyclo[(N-alpha x-Alloc)Dpr-alpha-azido-beta-aminopropanoyl-(N-alpha-Fmoc)Dpr-beta-Ala] (2), composed of orthogonally protected 2,3diaminopropanoyl (Dpr) and P-alanyl residues, have been described. Fmoc chemistry on a backbone amide linker derivatized resin has been used for the chain assembly. Selective removal of the 4-methyltrityl (Mtt) and 1-methyl-l-phenylethyl protections (PhiPr) exposes the beta-amino and carboxyl tenninus, respectively, and on-resin cyclization then gives the desired orthogonally protected cyclo-beta-tetrapeptides (1 and 2). The alpha-amino groups, bearing the Fmoc and Alloc protections and the azide mask, allow stepwise orthogonal derivatization of these solid-supported cyclo-beta-tetrapeptide cores (1 and 2). This has been demonstrated by attachments of various sugar units [viz., acetyl- or toluoyl-protected carboxymethyl alpha-D-glycopyranosides (13-15) and methyl 6-0-(4-nitrophetioxycarbonyl)-(X-D-cylycopyranosides (2224)] to obtain diverse di- and trivalent glycoclusters (33-42). Acidolytic release (TFA) from the support, followed by conventional NaOMe-catalyzed transesterification (33-40) or hydrazine-induced acyl substitution in DMF (41 and 42), gives the fully deprotected clusters (43-52) as final products.
Two novel peptide scaffolds, viz. cyclo[(N-alpha-Alloc)Dpr-beta-Ala-(N-alpha-Fmoc)Dpr-beta-Ala] (1) and cyclo[(N-alpha x-Alloc)Dpr-alpha-azido-beta-aminopropanoyl-(N-alpha-Fmoc)Dpr-beta-Ala] (2), composed of orthogonally protected 2,3diaminopropanoyl (Dpr) and P-alanyl residues, have been described. Fmoc chemistry on a backbone amide linker derivatized resin has been used for the chain assembly. Selective removal of the 4-methyltrityl (Mtt) and 1-methyl-l-phenylethyl protections (PhiPr) exposes the beta-amino and carboxyl tenninus, respectively, and on-resin cyclization then gives the desired orthogonally protected cyclo-beta-tetrapeptides (1 and 2). The alpha-amino groups, bearing the Fmoc and Alloc protections and the azide mask, allow stepwise orthogonal derivatization of these solid-supported cyclo-beta-tetrapeptide cores (1 and 2). This has been demonstrated by attachments of various sugar units [viz., acetyl- or toluoyl-protected carboxymethyl alpha-D-glycopyranosides (13-15) and methyl 6-0-(4-nitrophetioxycarbonyl)-(X-D-cylycopyranosides (2224)] to obtain diverse di- and trivalent glycoclusters (33-42). Acidolytic release (TFA) from the support, followed by conventional NaOMe-catalyzed transesterification (33-40) or hydrazine-induced acyl substitution in DMF (41 and 42), gives the fully deprotected clusters (43-52) as final products.
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