Total Synthesis of Ileabethoxazole, Pseudopteroxazole, and seco-Pseudopteroxazole

Abstract

The total syntheses of ileabethoxazole, pseudopteroxazole, and seco-pseudopteroxazole, three antituberculosis diterpenoids that had been isolated from Pseudopterogorgia elisabethae, were accomplished in a collective fashion. A cascade alkyne carbopalladation/Stille reaction was exploited to construct a triene precursor with suitable geometry. A fully substituted arene was then assembled through a key 6π electrocyclization/aromatization sequence, and served as an advanced common intermediate. Two radical cyclizations led to the formation of the five- and six-membered rings of ileabethoxazole and pseudopteroxazole, respectively, with the desired stereochemistry, and a straightforward side-chain elongation delivered seco-pseudopteroxazole.

Keywords: arenes; diterpenoids; electrocyclization; radical reactions; total synthesis.