Total Synthesis of Brevianamides X, Y and Z

Abstract

Brevianamides X (1) and Y (2) are relatively new members of the bicyclo[2.2.2]diazaoctane alkaloid family, whose biosynthetic origins remain unresolved. We report the asymmetric total synthesis of (+)-brevianamides Y (2), Z (16) and (+/-) brevianamide X (1) through a hydroxyproline-guided cascade. Oxidation timing governs divergence, affording concise routes and underscoring hydroxyproline as a privileged scaffold.