Improved solid-phase synthesis and study of arylopeptoids with conformation-directing side chains

Thomas Hjelmgaard (1) , Sophie Faure (2) , Emiliana de Santis (3) , Dan Staerk (1) , Bruce D. Alexander (4) , Alison A. Edwards (3) , Claude Taillefumier (2) , John Nielsen (1)

1 Department of Basic Sciences and Environment
2 SEESIB - Synthèse et étude de systèmes à intêret biologique
3 Medway School of Pharmacy
4 School of Science

The development of an improved methodology for iterative solid-phase synthesis of para- and metaarylopeptoids (oligomeric N-substituted aminomethyl benzamides) using benzoyl chloride building blocks is described. This methodology has enabled the synthesis of arylopeptoids with tert-butyl and phenyl side chains, which allows for complete control over the amide conformation: the tert-butyl results in a 100% cis amide conformation while the phenyl side chain results in a 100% trans amide conformation. The method has furthermore enabled the first synthesis and preliminary conformational studies of arylopeptoids bearing (S)-N-(1-phenylethyl) side chains.

Mots clés: Foldamers Aromatic oligoamides Peptoids Solid-phase synthesis Conformational analysis

Thomas Hjelmgaard, Sophie Faure, Emiliana de Santis, Dan Staerk, Bruce D. Alexander, et al.. Improved solid-phase synthesis and study of arylopeptoids with conformation-directing side chains. Tetrahedron, 2012, 68, pp.4444-4454. ⟨hal-00709292⟩