Constrained Cyclic β,γ‐Diamino Acids from Glutamic Acid: Synthesis of Both Diastereomers and Unexpected Kinetic Resolution

Abstract

We describe here an efficient synthesis of both diastereomers of cyclic β,γ‐diamino acids starting from l‐glutamic acid, based on the Blaise reaction. We show that by changing the protecting group, we can access either the five‐membered‐ring lactam, which can be used as a β‐amino acid, or the six‐membered‐ring lactam, as a γ‐amino acid. We also discovered an interesting kinetic resolution during the synthesis that allowed easier separation of diastereomers. The products can be easily used in peptide synthesis, and a tetramer with alternating trans cyclic γ‐amino acid and AIB (2‐aminoisobutyric acid) residues was synthesized.

Gramicidin‐S‐Inspired Cyclopeptidomimetics as Potent Membrane‐Active Bactericidal Agents with Therapeutic Potential

“…However, to date, there is no systematically applicable antibiotic based on GS available and thus a constant investment in this field is needed. Our group is strongly involved in the synthesis of β,γ‐diamino acids (β,γ‐DiAAs) as well as their incorporation in peptide chains [38–41] . We have reported several studies which established the possible involvement of the supplemental amino groups in extra hydrogen bonds [39,40] .…”

“…Our group is strongly involved in the synthesis of β,γ-diamino acids (β,γ-DiAAs) as well as their incorporation in peptide chains. [38][39][40][41] We have reported several studies which established the possible involvement of the supplemental amino groups in extra hydrogen bonds. [39,40] More recently, we have demonstrated that the replacement of D Phe-Pro in the β-turn region by turn mimics β,γ-diamino acids (β,γ-DiAAs) affords GS analogues endowed with retained activity but no hemolytic effect.…”

Unexpected dimerization of a tripeptide comprising a β,γ‐diamino acid

“…In our group, we have been dedicated on construction of structurally diverse β,γ‐diamino acids . When included in short peptides, they act as turn inducer to construct stable structures or optimize bioactive molecules . In this work, we show that another tripeptide with different configuration (Figure ) does no longer form any intramolecular hydrogen bond but induces intermolecular interaction.…”

Synthesis and Biological Evaluation of NH2-Sulfonyl Oseltamivir Analogues as Influenza Neuraminidase Inhibitors

“…The synthetic route of the target compounds is depicted in Scheme 1. Oseltamivir was reacted with the corresponding sulfonyl chlorides to obtain 3a – 3k [18,25,26]. The nitro fragment of 3i – 3k was reduced to amino by iron powder to afford intermediates 5i – 5k .…”