During the past years, we have explored the Diels-Alder chemistry of 3,5-dibromo-2-pyrone as a new diene synthon. Its synthetic versatility has been further exuberated by the recent discovery that either of the two C-Br groups can be selectively functionalized through transition metal catalyzed coupling reactions. The resultant 3- or 5-substituted 2-pyrones are also potent neutral dienes, and therefore may undergo cycloaddition reactions to afford an array of densely functionalized cyclohexenes. Ever since then, we have explored the potential applicability of the rich chemistry embedded in the 2-pyrone cycloadducts, toward the synthesis of complex bioactive natural products, which allowed us to achieve successful total syntheses of various natural products including crinine, crinamine, galanthamine, aspidospermidine, pancratistatin, 1-deoxylycorine, and lycorine. In conjunction to our continuous efforts toward target-oriented synthesis, we have devised a new synthetic route to (+)-aplykurodinone-1 by way of an efficient streo-, regio-selective intramolecular Diels-Alder reaction. This highly selective IMDA reaction could form tricyclic ring core with complete control of all stereo-centers at C3, C4, C7, C8 positions of aplykurodionone-1. Presented herein would be our recent results on the formal synthesis of (+)-aplykurodinone-1 and the efforts toward its total synthesis.