From soybean hulls to selenium-containing levoglucosenone derivatives: Synthesis and evaluation as urease inhibitors

Levoglucosenone, a renewable platform molecule obtained from soybean hull biomass, was used as a starting material for the synthesis of new organoselenium derivatives as urease inhibitors. Two complementary synthetic methodologies enabled selective access to C-4 diastereomers through Michael-type addition reactions under acid- or base-controlled conditions, affording the corresponding selenium-containing compounds in moderate to very good yields (26–91%). The stereochemical outcome was rationalized in terms of kinetic versus thermodynamic control and supported by NMR analysis. The Zn/EtOAc/HCl methodology enabled product isolation by recrystallization in several cases, reducing solvent consumption and improving process sustainability. The synthesized compounds were evaluated in vitro against jack bean urease and displayed significant inhibitory activity. Among them, compound 4a exhibited the highest potency, with an IC 50 value of 1.17 μM, superior to that of the reference inhibitor thiourea (IC 50 = 21.98 μM). Preliminary structure–activity trends suggest that both the nature of the selenium substituent and stereochemistry at C-4 influence inhibitory potency. These results demonstrate the potential of biomass-derived levoglucosenone as a sustainable precursor for the development of bioactive organoselenium compounds of agricultural interest for improving nitrogen-use efficiency.