Asymmetric Total synthesis of Asperones A and B through Organocatalyzed Quinone [5 + 2] Cycloaddition.

Abstract

The first asymmetric total synthesis of the anti-inflammatory polyketides asperones A (1) and B (2) has been accomplished. Key synthetic steps include a Diels-Alder and retro-Diels-Alder cascade to construct the poly substituted phenol, an Al-Salen-catalyzed asymmetric cyanosilylation to form the tertiary alcohol of gregatin A, and an organocatalyzed intermolecular [5 + 2] cycloaddition of p-quinone with electron-deficient alkenes to build the crucial [3.2.1] octane core of asperones A (1) and B (2).