Succinimidyl Carbamate Derivatives from N-Protected α-Amino Acids and Dipeptides-Synthesis of Ureidopeptides and Oligourea/Peptide Hybrids

• Published in: European Journal of Organic Chemistry 2007-05, Vol.2007 (15), p.2511-2525
• Main Authors: Fischer, Lucile, Semetey, Vincent, Lozano, Jose-Manuel, Schaffner, Arnaud-Pierre, Briand, Jean-Paul, Didierjean, Claude, Guichard, Gilles
• Format: Article
• Language: English
• Subjects: Biochemistry, Molecular Biology; Life Sciences; Oligomers; Peptides; Peptidomimetics; Solid-phase synthesis; Urea
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200601010

The preparation of succinimidyl (1‐{[(alkyloxy)carbonyl]amino}‐1‐X‐methyl)carbamates (4) and succinimidyl [1‐(acylamino)‐1‐X‐methyl] carbamates (5) from a variety ofN‐Boc‐, ‐Z‐ or ‐Fmoc‐protected α‐amino acids and dipeptides as well as the carbamate structural characterization are described. We have previously shown that succinimidyl carbamates 5, derived from N‐Boc dipeptides, can serve as direct precursors of 1,3,5‐triazepan‐2,6‐diones, a novel class of conformationally constrained dipeptide mimetics. Herein, we have evaluated the use of these building blocks for the synthesis of ureido‐peptides (in solution and on solid support), peptidyl hydantoins, oligoureas and some oligo(urea/amide) hybrids. Conformational investigations by NMR of ureidotripeptide 6i and pentamer 10, consisting of alternating amides and ureas, suggested that folded conformations (i.e. a urea turn) characterized by a cis,trans (E,Z) geometry of the urea linkage are populated in both [D5]pyridine and [D6]DMSO solutions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)