10.1021/co300125m.s001
Agustina La Venia
Agustina La
Venia
Barbora Lemrová
Barbora
Lemrová
Viktor Krchňák
Viktor
Krchňák
Regioselective Incorporation
of Backbone Constraints
Compatible with Traditional Solid-Phase Peptide Synthesis
American Chemical Society
2013
nucleophilic addition
Regioselective Incorporation
peptide amide nitrogen
Backbone Constraints Compatible
regioselective formation
aldehyde
cyclic iminiums
nitrogen nucleophile
peptide amides
peptide backbone amide nitrogen
2013-01-14 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Regioselective_Incorporation_of_Backbone_Constraints_Compatible_with_Traditional_Solid_Phase_Peptide_Synthesis/2452678
A 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 <i>N</i>-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 <i>N</i>-acyliminium ion cyclization-nucleophilic addition. The outcome of
this nucleophilic addition was dependent on the substituent on the
nitrogen nucleophile.