Innovative On-Resin and in Solution Peptidomimetics Synthesis via Metal-Free Photocatalytic Approach.

Autor: Gandini T; Dipartimento di Scienze Farmaceutiche, Sez. Chimica Generale e Organica A. Marchesini, Università degli Studi di Milano, Via Venezian 21, 20133, Milan, Italy., Vaghi F; Dipartimento di Scienze Chimiche, Università degli Studi di Padova, Via Marzolo 1, 35131, Padova, Italy., Laface Z; Dipartimento di Scienze Farmaceutiche, Sez. Chimica Generale e Organica A. Marchesini, Università degli Studi di Milano, Via Venezian 21, 20133, Milan, Italy., Macetti G; Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133, Milan, Italy., Bossi A; Istituto di Scienze e Tecnologie Chimiche 'G. Natta' (SCITEC), Centro Nazionale Ricerche, Via Fantoli 16/15, 20138, Milano, Italy., Penconi M; Istituto di Scienze e Tecnologie Chimiche 'G. Natta' (SCITEC), Centro Nazionale Ricerche, Via Fantoli 16/15, 20138, Milano, Italy., Luisa Gelmi M; Dipartimento di Scienze Farmaceutiche, Sez. Chimica Generale e Organica A. Marchesini, Università degli Studi di Milano, Via Venezian 21, 20133, Milan, Italy., Bucci R; Dipartimento di Scienze Farmaceutiche, Sez. Chimica Generale e Organica A. Marchesini, Università degli Studi di Milano, Via Venezian 21, 20133, Milan, Italy.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2024 Dec 05; Vol. 30 (68), pp. e202402790. Date of Electronic Publication: 2024 Nov 08.
DOI: 10.1002/chem.202402790
Abstrakt: Nowadays, peptidomimetics are widely studied, being useful tools in drug discovery and medicinal chemistry. The coupling between a carboxylic acid with an amine to form a peptide bond is the most common reaction to obtain peptides/peptidomimetics. In this work, we have investigated an innovative metal-free photoredox-catalyzed carbamoylation to form peptidomimetics thanks to the reaction between dihydropyridines functionalized with amino acids (or peptide sequences) and differently functionalized imines. As the organic photocatalyst, we used 4CzIPN, a donor-acceptor cyanoarene vastly used in photoredox catalysis. By easily modulating the amino acid (or peptide sequence), which is directly attached to the dihydropyridine, we proposed this key-reaction as new valuable method to obtain peptidomimetics, in situ building the not-natural portion of the sequence. Moreover, we successfully employed this methodology in solid phase peptide synthesis, both inserting the new photoredox-generated amino acid at the end or in the middle of the sequence. Peptides with different lengths and secondary structures were prepared, proving the success of this approach, even in sterically hindered environment. Herein, to the best of our knowledge, we describe the first photocatalytic protocol which allows the building of the peptide backbone, with the possibility of simultaneously inserting a non-coded amino acid in the sequence.
(© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)
Databáze: MEDLINE
Externí odkaz: