A stereodivergent strategy to obtain enantiopure cis and trans 4-aminopipecolic acids (4-APAs) in a suitably protected form for peptide synthesis has been devised starting from a common, known precursor in turn easily prepared from commercial (R)-4-cyano-3-hydroxybutyric acid ethyl ester. The two isomers were efficiently obtained in 40 % and 23 % overall yields, respectively, in seven and ten steps. To demonstrate their usefulness in peptidomimetic synthesis, both 4-APA isomers were incorporated as γ-amino acids in a cyclic RGD-containing sequence, although for the trans 4-APA isomer a further amino acid in the sequence (L-Phe) was needed to allow ring closure. The two cyclopeptides were tested as αVβ3 integrin antagonists in comparison with cilengitide.
Enantioselective Synthesis of cis and trans 4-Aminopipecolic Acids as γ-Amino Acids for the Construction of Cyclic RGD-Containing Peptidomimetics Antagonists of αVβ3 Integrin / F. Dordoni, D. Scarpi, F. Bianchini, A. Contini, E.G. Occhiato. - In: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1434-193X. - 2020:28(2020 Aug 02), pp. 4371-4383.
|Titolo:||Enantioselective Synthesis of cis and trans 4-Aminopipecolic Acids as γ-Amino Acids for the Construction of Cyclic RGD-Containing Peptidomimetics Antagonists of αVβ3 Integrin|
CONTINI, ALESSANDRO (Penultimo)
|Parole Chiave:||4-Aminopipecolic acids; Integrins; Peptidomimetics; Synthetic methdos|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
|Data di pubblicazione:||2-ago-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/ejoc.202000634|
|Appare nelle tipologie:||01 - Articolo su periodico|