Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

Abstract

The synthesis of a novel category of pseudo-peptides via intramolecular Ugi reaction of levulinic acid (4-oxopentanoic acid), aromatic and aliphatic amines, and amino acid-based isocyanides is reported. Levulinic acid was applied as a bifunctional substrate containing both carbonyl and acid moieties suitable for the Ugi reaction. This article provides a facile and convenient one-pot procedure for the synthesis of peptide-like heterocyclic molecules containing 2-pyrrolidone (γ-lactam), amide and ester functional groups with good to excellent yields.

Synthesis of Various N‐heterocycles Using the Ugi Four‐Center Three‐Component Reaction

“…A facile and convenient one‐pot synthesis of a novel category of pseudo‐peptides containing γ‐lactam 9 was achieved and reported based on a U‐4 C‐3CR of levulinic acid, amino acid‐based isocyanides, and aromatic and aliphatic amines under mild reaction conditions for 24 h (Scheme ) …”

Multifunctionalized Polyamides Prepared by Facile Ugi Reaction as Thermosensitive, Biocompatible and Antibacterial Biomaterials

“…Theoretically, as long as two reactants in Ugi reaction are bifunctional compounds such as dicarboxylic acids (or dialdehydes, diisocyanides and diamines), or one reactant contains two different functional groups such as amino acids (or carboxyl aldehydes), Ugi reaction evolve into a linear polymerization system i. e. Ugi four‐component polymerization (Ugi‐4CP) . Obviously, the three‐dimensional polymerization can be realized as more than two bifunctional reactants, or one reactant with three functional groups are introduced into Ugi reaction system . It′s worth noting that in Ugi‐4CP, the aldehyde component with a blocked α position, such as in benzaldehyde or isobutyraldehyde can effectively avoid the side reactions .…”

“…[1,2,4] Obviously, the three-dimensional polymerization can be realized as more than two bifunctional reactants, or one reactant with three functional groups are introduced into Ugi reaction system. [2,[14][15][16][17] It's worth noting that in Ugi-4CP, the aldehyde component with a blocked α position, such as in benzaldehyde or isobutyraldehyde can effectively avoid the side reactions. [1] The moderate water can accelerate Ugi-4CP, but not promote the increase of molecular weight of polymers.…”