The growing interest in the 1,4-disubstituted-1,2,3-triazolyl moiety as an amide bond surrogate and its formation through very mild, chemoselective, and bioorthogonal CuI-catalyzed Huisgen 1,3-dipolar [3+2] cycloaddition of an alkynyl to an azido function, presented an unmet need for specifically designed α-amino-acid-derived building blocks. Herein we report the synthesis of unnatural homologous series of Nα- Fmoc-protected ω-yne- and ω-azido-L-amino acids compatible with the Fmoc/tBu-based solid-phase peptide synthesis. These building blocks can be incorporated into pseudopeptides that can serve as precursors of inter- and intramolecular click reactions. The homologous Nα-Fmoc-ω-azido-L-amino acids were prepared from either the ω-amino or the ω-hy-droxy precursors by the respective diazo-transfer reactions and sequential nucleophilic substitutions initially by halide followed by azide. The homologous Nα-Fmoc-ω-yne-L-amino acids were prepared by alkylation of a chiral auxiliary, which is a NiII complex of Schiff base derived from glycine and (S)- 2-(N-benzylprolyl)aminobenzophenone, with ω-bromoalkynes. These building blocks will be instrumental for constructing side-chain modified peptides, interside-chain peptide chimera, peptide small molecule conjugates, and cyclopeptides, which were cyclized through 1,4-disubstituted 1,2,3-triazolyl-containing side-chain-to-side-chain bridges.

N(alpha)-Fmoc-Protected omega-Azido and omega-Ynoic-alpha-Amino Acids as Building Blocks for the Synthesis of "Clickable" Peptides / A. Le Chevalier Isaad; F. Barbetti; P. Rovero; A. D’Ursi; M. Chelli; M. Chorev; A.M. Papini. - In: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1434-193X. - STAMPA. - 31:(2008), pp. 5308-5314. [10.1002/ejoc.200800717]

N(alpha)-Fmoc-Protected omega-Azido and omega-Ynoic-alpha-Amino Acids as Building Blocks for the Synthesis of "Clickable" Peptides

ROVERO, PAOLO;M. Chelli;PAPINI, ANNA MARIA
2008

Abstract

The growing interest in the 1,4-disubstituted-1,2,3-triazolyl moiety as an amide bond surrogate and its formation through very mild, chemoselective, and bioorthogonal CuI-catalyzed Huisgen 1,3-dipolar [3+2] cycloaddition of an alkynyl to an azido function, presented an unmet need for specifically designed α-amino-acid-derived building blocks. Herein we report the synthesis of unnatural homologous series of Nα- Fmoc-protected ω-yne- and ω-azido-L-amino acids compatible with the Fmoc/tBu-based solid-phase peptide synthesis. These building blocks can be incorporated into pseudopeptides that can serve as precursors of inter- and intramolecular click reactions. The homologous Nα-Fmoc-ω-azido-L-amino acids were prepared from either the ω-amino or the ω-hy-droxy precursors by the respective diazo-transfer reactions and sequential nucleophilic substitutions initially by halide followed by azide. The homologous Nα-Fmoc-ω-yne-L-amino acids were prepared by alkylation of a chiral auxiliary, which is a NiII complex of Schiff base derived from glycine and (S)- 2-(N-benzylprolyl)aminobenzophenone, with ω-bromoalkynes. These building blocks will be instrumental for constructing side-chain modified peptides, interside-chain peptide chimera, peptide small molecule conjugates, and cyclopeptides, which were cyclized through 1,4-disubstituted 1,2,3-triazolyl-containing side-chain-to-side-chain bridges.
31
5308
5314
A. Le Chevalier Isaad; F. Barbetti; P. Rovero; A. D’Ursi; M. Chelli; M. Chorev; A.M. Papini
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/351103
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