co300125m_si_001.pdf (1.86 MB)
Regioselective Incorporation of Backbone Constraints Compatible with Traditional Solid-Phase Peptide Synthesis
journal contribution
posted on 2013-01-14, 00:00 authored by Agustina La Venia, Barbora Lemrová, Viktor KrchňákA protected aldehyde was attached via a two-carbon spacer
to a
peptide backbone amide nitrogen during a traditional Merrifield solid-phase
synthesis. Acid-mediated unmasking of the aldehyde triggered the regioselective
formation of cyclic N-acyliminiums between the aldehyde
and the neighboring peptide amide nitrogen. In the absence of an internal
nucleophile, the cyclic iminiums formed dihydropyrazinones, a six-membered
peptide backbone constraint between two peptide amides. In the presence
of an internal nucleophile, tetrahydropyrazinopyrimidinediones or
tetrahydroimidazopyrazinediones were formed via tandem N-acyliminium ion cyclization-nucleophilic addition. The outcome of
this nucleophilic addition was dependent on the substituent on the
nitrogen nucleophile.