Novel tetronamides derived from mucobromic acid: synthesis, structural elucidation, DFT calculations and phytotoxic...

Motivated by the growing demand for increased food production and the need to identify new, more selective and effective herbicides in view of the resistance developed by plants to traditional herbicides, we synthesized six novel tetronamides derived from mucobromic acid and menthol. The structures of these compounds were characterized by spectroscopic techniques, complemented by theoretical calculations based on Density Functional Theory (DFT). In addition, we evaluated the phytotoxic activity of these substances in species such as Cucumis sativus, Solanum lycopersicum, Sorghum bicolor L. Moench, Urochloa brizantha and Bidens pilosa.

The acyclic form of mucobromic acid was activated by (1S)-(+)-10-camphorsulfonic acid (CSA) for the enantioselective synthesis of compound 1b, which served as a starting point for the aza-Michael addition/elimination reaction on the butenolide ring. In this reaction, the carbon at the C4 position was activated, allowing the nucleophilic attack by different substituted anilines, giving rise to the new tetronamides 2b-7b. The relative configuration of the chiral centers of these substances was defined as SRSR based on spectroscopic analysis, theoretical calculations and the probabilistic methods DP4, DP4+, Linear Regression (R²), and Corrected Mean Absolute Error (CMAE). The bioassays performed indicated significant inhibition of the growth of roots and shoots of U. brizantha.

These results confirm the potential of these tetronamides as selective phytotoxic agents and pave the way for the future development of more effective and sustainable herbicides, contributing to intelligent weed management and increased agricultural productivity. © 2026 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.