Trial and Error in Total Synthesis of Polyketide-derived Polycyclic Natural Products

摘要

Herein, our synthetic strategies toward polyketide-derived polycyclic compounds are described. Our approaches are based on the construction of isoxazole-fused polycyclic structure with an angular hydroxy group via (1) annulation via benzonitrile oxide and (2) benzoin cyclization. Also described is the stereocontrolled introduction of angular substituents via pinacol-type 1,2-shift and N-methylation/hydroxylation, paving a way to advanced intermediates. The synthetic utility has been highlighted by successful total syntheses of some structurally complex, polycyclic natural products, such as BE-43472B, pleospdione, and tetracenomycin C.