Solid-Phase Synthesis of Peptide Thioureas and Thiazole-Containing Macrocycles through Ru-Catalyzed Ring-Closing Metathesis
2013; American Chemical Society; Volume: 16; Issue: 2 Linguagem: Inglês
10.1021/co400102v
ISSN2156-8952
AutoresA. Emil Cohrt, Thomas E. Nielsen,
Tópico(s)Click Chemistry and Applications
ResumoN-Terminally modified α-thiourea peptides can selectively be synthesized on solid support under mild reaction conditions using N,N′-di-Boc-thiourea and Mukaiyama's reagent (2-chloro-1-methyl-pyridinium iodide). This N-terminal modification applies to the 20 proteinogenic amino acid residues on three commonly used resins for solid-phase synthesis. Complementary methods for the synthesis of α-guanidino peptides have also been developed. The thiourea products underwent quantitative reactions with α-halo ketones to form thiazoles in excellent purities and yields. When strategically installed between two alkene moieties, said thiazole core was conveniently embedded in peptide macrocycles via Ru-catalyzed ring-closing metathesis reactions. Various 15–17 membered macrocycles were easily accessible in all diastereomeric forms using this methodology. The developed "build/couple/pair" strategy is well suited for the generation of larger and stereochemically complete screening libraries of thiazole-containing peptide macrocycles.
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