Total Synthesis of Novel Bioactive Natural Product Paracaseolide A and Analogues: Computational Evaluation of a ′Proposed′ Biomimetic Diels—Alder Reaction.

A short and generally applicable synthesis of bioactive tetracyclic natural product paracaseolide A has been accomplished employing a ‘proposed’ biomimetic Diels–Alder reaction as the key strategic step. The Diels–Alder precursors for this purpose were readily assembled through a versatile Suzuki coupling on preformed α-halo butenolides. The mechanistic aspects of the ‘putative’ biomimetic Diels–Alder reaction have been probed using computational methods, which suggest that this [4+2]-cycloaddition proceeds through a step-wise process and product profile is thermodynamically governed.