The total synthesis of 1-O-methyllateriflorone (2) is described. The construction of the cage-like domain of the molecule involved a biomimetic Claisen/Diels-Alder cascade, whereas the novel spiroxa-lactone framework was generated by an intramolecular Michael reaction within precursor 16a involving the carboxylate residue as the nucleophile. This finding might bear on the biosynthetic pathway by which nature forms lateriflorone. Described herein is also an interesting cascade sequence involving facile 6 T electrocyclizations which leads to complex benzopyran systems. The biological evaluation of a small library of lateriflorone analogues and related systems establishing the first SAR within this class of compounds is also included. Among the most active compounds against tumor cells are 2, 16b, 56, 58, and 59.