| Abstract
| - Among pseudopeptidic foldamers, aza-β3-peptides have the unique property to possess nitrogenstereocenters instead of carbon stereocenters. As the result of pyramidal inversion at Nα-atoms along thebackbone, they behave as a set of C8-based secondary structures in equilibrium. This structural modulationis exploited here to prepare 24-membered macrocycles with great efficiency. Both crystal structures andspectroscopic data establish that aza-β3-cyclohexapeptides adopt a highly organized conformation wherethe relative configuration of chiral nitrogen atoms is alternated. This makes them an interesting scaffoldas the stereocontrol occurs spontaneously through the cyclization. These compounds reveal anunprecedented slow pyramidal nitrogen inversion in macrocycles. Pyramidal ground state stabilization,hindered rotation, steric crowding, and H-bond cooperativity are proposed to participate in this strikingphenomenon. The equilibrium between invertomers of aza-β3-cyclohexapeptides is reminiscent of theinterchange between the two chair forms of cyclohexane.
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