Synthesis of Some 2,2′:6′,2″‐Terpyridines Disubstituted in Positions 6 and 6″ with Head‐to‐Tail Oriented Amino Acids and Dipeptides: A Simple Entry to a Reversible Inducer of Folding in Amino Acid Sequences

The 2,2′:6′,2″‐terpyridine scaffold has been identified as a conformationally discrete structural element potentially capable of inducing reversible folding in substituents, attached through suitable spacers to its 6,6″‐positions, by metal complexation/decomplexation or by protonation/deprotonation. The synthesis of some terpyridine–amino acids and terpyridine–dipeptide conjugates is described. The assembly of these conjugates has been achieved by connecting NH 2 ‐ and CO 2 H‐protected glycine, alanine, and valine residues or antiparallel oriented AlaGly/GlyAla chains to the terpyridine scaffold through phenylacetylene spacers. Preliminary experiments showed that upon addition of Zn 2+ to the amino acid substituted transoid terpyridine systems, folded cisoid complexes were formed. Also, bis(protonation) of the dipeptide‐substituted system resulted in the formation of a folded adduct. Reversibility of the folding process was shown by Zn 2+ removal with triethylamine or deprotonation with aqueous ammonia. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)