Substituted imidazo[1,2-a]pyridines as β-strand peptidomimetics

Abstract

New conformationally extended dipeptide surrogates based on an imidazo[1,2-a]pyridine scaffold are described. Efficient synthesis and incorporation into host peptides affords structures with native side-chain functionality and hydrogen bonding elements on one face of the backbone. Structural analysis by NMR suggests that model peptidomimetics adopt a β-strand-like conformation in solution.

Figure 1

Design of IP-based β-strand mimics.

Figure 2

ROESY spectrum of 8 (500 MHz in CDCl₃) highlighting key Overhauser correlations.

Figure 3

Structures of possible turn conformations of 8.

Scheme 1

Synthesis of orthogonally-protected IP-based extended dipeptide surrogates.

Scheme 2

Synthesis and selected ROESY correlations (in red) of tetrapeptide mimic 6.

Scheme 3

Synthesis of heptapeptide mimic 8 and conformational analysis by ¹H NMR.