Progress toward the total synthesis of psiguadial B

Abstract

Progress toward the total synthesis of psiguadial B, a diformyl phloroglucinol meroterpenoid natural product, is disclosed. The synthetic strategy employed has resulted in the development of three key transformations: a photochem. Wolff rearrangement with tandem asym. ketene addn., a palladium-catalyzed C(sp )-H activation reaction of a cyclobutane substrate, and an inverse-electron demand hetero-Diels Alder cycloaddn. between a highly-oxidized ortho-quinone methide and a cyclohexanone-derived enol ether. This strategy enables rapid assembly of the tricylic core of psiguadial B, with de novo construction of the transfused cyclobutane ring found in several natural products in this family. Current efforts directed toward developing a successful cyclization reaction to form a highly strained seven-membered ring will also be presented.