Synthesis and Characterisation of Helical β-Peptide Architectures that Contain (S)-β3-HDOPA(Crown Ether) Derivatives

A new set of β‐amino acids that carry various crown ether receptors on their side chains of the general formula (S)‐β3‐HDOPA(crown ether) (HDOPA: homo‐3,4‐dihydroxyphenylalanine; (crown ether): [15]crown‐5 ([15‐C‐5]), [18]crown‐6 ([18‐C‐6]), [21]crown‐7 ([21‐C‐7]), 1,2‐Benzo‐[24]crown‐8 ([Benzo‐24‐C‐8]) and (R)‐Binol‐[20]crown‐6 ([(R)‐Binol‐20‐C‐6])) was prepared. Peptides that are based on these new crowned β‐amino acids combined with (1S,2S)‐ACHC (2‐aminocyclohexanecarboxylic acid), which is known to be a potent 314‐helix inducer, to the hexamer level, with two crowned residues at the i and i+3 positions of the main‐chain, were synthesized in solution by stepwise coupling using Boc‐Nα‐protection (Boc: tert‐butoxycarbonyl) and the EDC/HOAt C‐activation method. Their conformational analysis was performed by using FTIR absorption, NMR and CD spectroscopy techniques. Our results are in full agreement with a 314‐helix conformation. Crowned peptides: A new set of β‐amino acids that carry various crown ether receptors was prepared. FTIR absorption, NMR and CD data (see figure) are in full agreement with a 14‐helix structure for all of the crowned β‐hexapeptides synthesised. Therefore, crown ether residues that are aligned on one helix face at the i and i+3 positions offer the opportunity for a cooperative cation binding. This structural study is an initial step towards the exploitation of helical, crowned peptides for functional uses.