Alantolactone and isoalantolactone, naturally occurring sesquiterpene lactones, are known for their significant pharmacol. properties, including anti-inflammatory, anticancer, and antimicrobial activities.However, their biol. potential can be further enhanced by structural modification.In this study, we report a diversity-oriented semi-synthesis of novel alantolactone and isoalantolactone hybrids through an azomethine ylide cycloaddition pathway.This efficient process allowed us to create complex and diverse mol. structures.Specifically, we focused on modifying the, α, β-unsaturated exocyclic double bond from butyrolactone core to produce dispirohybrids, including compounds like dispirooxindolo, indanedione, and acenaphthylen-2-one, using amino acids and diketones.The synthesized hybrids were fully characterized using various spectroscopic techniques (1D, 2D-NMR, HRMS, and X-ray diffraction).In silico studies revealed favorable drug-like properties for the synthesized spirocompounds, including ideal physicochem. characteristics, promising pharmacokinetic behavior, excellent oral bioavailability, and minimal toxicity risk.These predictions highlight the potential of these spiroderivatives as strong candidates for further development in drug discovery.This work shows that the azomethine ylide cycloaddition is a useful method for enhancing the chem. and biol. diversity of natural products.