Biomimetic Synthesis of an Antiviral Cinnamoylphloroglucinol Collection from Cleistocalyx operculatus: A Synthetic Strategy Based on Biogenetic Building Blocks

Abstract

AbstractA synthetic strategy based on biogenetic building blocks for the collective and divergent biomimetic synthesis of cleistoperlones A−F, a cinnamoylphloroglucinol collection discovered from Cleistocalyx operculatus, has been developed. These syntheses proceeded successfully in only six to seven steps starting from commercially available 1,3,5‐benzenetriol and involving oxidative activation of stable biogenetic building blocks as a crucial step. Key features of the syntheses include a unique Michael addition/ketalization/1,6‐addition/enol‐keto tautomerism cascade reaction for the construction of the dihydropyrano[3,2‐d]xanthene tetracyclic core of cleistoperlones A and B, and a rare inverse‐electron‐demand hetero‐Diels–Alder cycloaddition for the establishment of benzopyran ring in cleistoperlones D−F. Moreover, cleistoperlone A exhibited significant antiviral activity against acyclovir‐resistant strains of herpes simplex virus type 1 (HSV‐1/Blue and HSV‐1/153).