Abstract
A library of isopulegol-based β-amino acid derivatives has been developed from commercially-available (-)-isopulegol. Michael addition of primary and secondary amines towards α,β-unsaturated γ-lactones was accomplished resulting in β-aminolactones in highly-stereoselective reactions. Ring-opening of β-aminolactones with different amines furnished excellent yields of β-aminoamides. Moreover, the applicability of aminolactones in peptide synthesis was examined by opening the lactone ring with α- and β-aminoesters, providing dipeptides as promising chiral substrates for the synthesis of foldamers. The antiproliferative activities of β-aminolactones and β-aminoamides were explored, and the structure-activity relationships were studied from the aspects of the stereochemistry of the monoterpene ring and the substituent effects on the β-aminoamide ring system. The N-unsubstituted (-)-isopulegol-based β-aminoamides exhibited considerable antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, MCF7 and MDA-MB-231).
Highlights
Sesquiterpene lactones containing the α-methylene-γ-lactone moiety are natural products occurring in many plant families
Besides interest in the synthesis of β-aminoamides, the opening of β-aminolactones with β-aminoesters is a useful method for the synthesis of dipeptides containing β-alanine moiety. β-Alanine is a precursor of the antioxidant dipeptide carnosine (β-alanine-L-histidine), which is thought to increase cell viability via an anti-senescence mechanism [21]. β-Ala-Gln has been applied in medical fields as a component of patient infusions [22]
Starting from commercially-available (-)-isopugeol, a new family of isopulegol- and neoisopulegol-based chiral β-aminolactone and β-aminoamide libraries has been prepared through chiral α-methylene-γ-lactones as key intermediates
Summary
Sesquiterpene lactones containing the α-methylene-γ-lactone moiety are natural products occurring in many plant families These compounds are known for their various biological activities, including cytotoxicity to tumor cells, anti-bacterial, antifungal, and anti-protozoan activities, as well as activity against human and animal parasites or inhibition of plant growth [1,2,3]. 1,3-aminalcohols, proved to use those chiral auxiliaries in the enantioselective synthesis of secondary alcohols or other pharmacons, e.g., esomeprazole [5,6,7,8,9] Besides their value in enantioselective catalysis, 1,3-aminoalcohols are excellent building blocks for the synthesis of various heterocyclic ring systems, such as 1,3-oxazines, 1,3-thiazines or 1,4-oxazepams [10,11]. Besides interest in the synthesis of β-aminoamides, the opening of β-aminolactones with β-aminoesters is a useful method for the synthesis of dipeptides containing β-alanine moiety. Β-alanine transporters were found to be highly upregulated in antibody-producing cell lines, indicating the cell’s requirement for this amino acid [21]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
