Depsipeptides are biologically active peptide derivatives that possess a high therapeutic interest. The development of depsipeptide mimics characterized by a chemical diversity could lead to compounds with enhanced features and activity. In this work, an on-resin multicomponent procedure for the synthesis of amidino depsipeptide mimics is described. This approach exploits a metal-free 1,3-dipolar cycloaddition of cyclopentanone–proline enamines and sulfonylazides. In this reaction, the obtained primary cycloadduct undergoes a ring opening and molecular rearrangement giving access to a linear sulfonyl amidine functionalized with both a peptide chain and a diazoalkane. The so-obtained diazo function “one pot” reacts with the carboxylic group of N-Fmoc-protected amino acids leading to amidino depsipeptide mimics possessing a C4 aliphatic chain. An important advantage of this procedure is the possibility to easily obtain amidino-functionalized derivatives that are proteolytically stable peptide bond bioisosteres. Moreover, the conformational freedom given by the alkyl chain could promote the obtainment of cyclic depsipeptide with a stabilized secondary structure as demonstrated with both in silico calculations and experimental conformational studies. Finally, labeled depsipeptide mimics can be also synthesized using a fluorescent sulfonylazide in the multicomponent reaction.
On-resin multicomponent 1,3-dipolar cycloaddition of cyclopentanone–proline enamines and sulfonylazides as an efficient tool for the synthesis of amidino depsipeptide mimics / R. Bucci, F. Dapiaggi, H. Macut, S. Pieraccini, M. Sironi, M.L. Gelmi, E. Erba, S. Pellegrino. - In: AMINO ACIDS. - ISSN 0939-4451. - (2019 Nov 28).
|Titolo:||On-resin multicomponent 1,3-dipolar cycloaddition of cyclopentanone–proline enamines and sulfonylazides as an efficient tool for the synthesis of amidino depsipeptide mimics|
BUCCI, RAFFAELLA (Primo) (Corresponding)
DAPIAGGI, FEDERICO (Secondo)
ERBA, EMANUELA (Penultimo)
PELLEGRINO, SARA (Ultimo) (Corresponding)
|Parole Chiave:||1,3-Dipolar cycloaddition; Depsipeptide mimics; Multicomponent reaction; Solid-phase synthesis|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
Settore CHIM/02 - Chimica Fisica
|Data di pubblicazione:||28-nov-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1007/s00726-019-02805-3|
|Appare nelle tipologie:||01 - Articolo su periodico|
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