Synthesis and Identification of Epoxy Derivatives of 5-Methylhexahydroisoindole-1,3-dione and Biological Evaluation

• Main Authors: Kariny B. A. Torrent, Elson S. Alvarenga
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Molecules
• Subjects: cyclic imide; theoretical calculations; DFT; CP3; DP4; herbicide
• Online Access: https://www.mdpi.com/1420-3049/26/7/1923

Cyclic imides belong to a well-known class of organic compounds with various biological activities, promoting a great interest in compounds with this functional group. Due to the structural complexity of some molecules and their spectra, it is necessary to use several spectrometric methods associated with auxiliary tools, such as the theoretical calculation for the structural elucidation of complex structures. In this work, the synthesis of epoxy derivatives of 5-methylhexahydroisoindole-1,3-diones was carried out in five steps. Diels–Alder reaction of isoprene and maleic anhydride followed by reaction with <i>m</i>-anisidine afforded the amide (<b>2</b>). Esterification of amide (<b>2</b>) with methanol in the presence of sulfuric acid provided the ester (<b>3</b>) that cyclized in situ to give imides <b>4</b> and <b>4-ent</b>. Epoxidation of <b>4</b> and <b>4-ent</b> with <i>meta</i>-chloroperbenzoic acid (MCPBA) afforded <b>5a</b> and <b>5b</b>. The diastereomers were separated by silica gel flash column chromatography, and their structures were determined by analyses of the spectrometric methods. Their structures were confirmed by matching the calculated ¹H and ¹³C NMR chemical shifts of (<b>5a</b> and <b>5b</b>) with the experimental data of the diastereomers using MAE, CP3, and DP4 statistical analyses. Biological assays were carried out to evaluate the potential herbicide activity of the imides. Compounds <b>5a</b> and <b>5b</b> inhibited root growth of the weed <i>Bidens pilosa</i> by more than 70% at all the concentrations evaluated.