Nucleation of <i>β</i>-Hairpin Structures with Cis Amide Bonds in <i>E</i>-Vinylogous Proline-Containing Peptides

Synthesis and conformational studies of peptides containing the <i>E</i>-vinylogous prolines <b>1</b> (VPro1) and <b>2</b> (VPro2), Boc-Ala-Val-VPro1-Xaa-Leu-OMe (<b>3</b>, Xaa = Gly; <b>4</b>, Xaa = Phe), Boc-Ala-Val-VPro2-Xaa-Leu-OMe (<b>5</b>, Xaa = Gly; <b>6</b>, Xaa = Phe), Boc-Leu-Ile-Val-VPro1-Xaa-Leu-OMe (<b>7</b>, Xaa = Gly; <b>8</b>, Xaa = Phe), and Boc-Leu-Ile-Val-VPro2-Xaa-Leu-OMe (<b>9</b>, Xaa = Gly; <b>10</b>, Xaa = Phe), were carried out. It has been shown that both VPro1 and VPro2 lead to the formation of 12-membered intramolecularly hydrogen bonded structures very similar to type VI <i>β</i>-turns with a cis Xaa−VPro amide bond in the major conformers in all the peptides <b>3</b>−<b>10</b>, resulting in the nucleation of β-hairpin type structures in these molecules in CDCl<sub>3</sub>.