In:
European Journal of Organic Chemistry, Wiley, Vol. 2008, No. 31 ( 2008-11), p. 5308-5314
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 Cu I ‐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 N α ‐Fmoc‐protected ω‐yne‐ and ω‐azido‐ L ‐amino acids compatible with the Fmoc/ t Bu‐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 N α ‐Fmoc‐ω‐azido‐ L ‐amino acids were prepared from either the ω‐amino or the ω‐hydroxy precursors by the respective diazo‐transfer reactions and sequential nucleophilic substitutions initially by halide followed by azide. The homologous N α ‐Fmoc‐ω‐yne‐ L ‐amino acids were prepared by alkylation of a chiral auxiliary, which is a Ni II 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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Type of Medium:
Online Resource
ISSN:
1434-193X
,
1099-0690
DOI:
10.1002/ejoc.v2008:31
DOI:
10.1002/ejoc.200800717
Language:
English
Publisher:
Wiley
Publication Date:
2008
detail.hit.zdb_id:
1475010-7
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