Synthesis and Transformation of (-)-Isopulegol-Based Chiral β-Aminolactones and β-Aminoamides

Tam Minh Le, Péter Bérdi, I. Zupkó, F. Fülöp, Z. Szakonyi

Research output: Contribution to journalArticle

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).

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume19
Issue number11
DOIs
Publication statusPublished - Nov 8 2018

Fingerprint

Amines
Monoterpenes
Lactones
Stereochemistry
rings
synthesis
Peptides
Amino acids
amines
Dipeptides
Cells
Structure-Activity Relationship
multiple docking adapters
Derivatives
Libraries
stereochemistry
Substrates
cultured cells
peptides
amino acids

Keywords

  • antiproliferative activity
  • dipeptide
  • terpenoid
  • β-aminoamides
  • β-aminolactones

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

@article{124ab6033ee6451ba9e2d5349a9e6d61,
title = "Synthesis and Transformation of (-)-Isopulegol-Based Chiral β-Aminolactones and β-Aminoamides",
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).",
keywords = "antiproliferative activity, dipeptide, terpenoid, β-aminoamides, β-aminolactones",
author = "Le, {Tam Minh} and P{\'e}ter B{\'e}rdi and I. Zupk{\'o} and F. F{\"u}l{\"o}p and Z. Szakonyi",
year = "2018",
month = "11",
day = "8",
doi = "10.3390/ijms19113522",
language = "English",
volume = "19",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "11",

}

TY - JOUR

T1 - Synthesis and Transformation of (-)-Isopulegol-Based Chiral β-Aminolactones and β-Aminoamides

AU - Le, Tam Minh

AU - Bérdi, Péter

AU - Zupkó, I.

AU - Fülöp, F.

AU - Szakonyi, Z.

PY - 2018/11/8

Y1 - 2018/11/8

N2 - 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).

AB - 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).

KW - antiproliferative activity

KW - dipeptide

KW - terpenoid

KW - β-aminoamides

KW - β-aminolactones

UR - http://www.scopus.com/inward/record.url?scp=85056375630&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056375630&partnerID=8YFLogxK

U2 - 10.3390/ijms19113522

DO - 10.3390/ijms19113522

M3 - Article

VL - 19

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 11

ER -