Bioinspired One-Step Oxidative Cleavage of Paxilline Enables Rapid Generation of Indole Diterpenoid Derivatives with Antibiofilm Activity

Abstract

Inspired by the biosynthesis of naturally occurring indole diterpenoids, employing paxilline as the foundational scaffold, we developed a one-step oxidative cleavage strategy that efficiently constructs novel ring systems through oxidant-controlled diversification. Furthermore, we deciphered the nonenzymatic formation pathway of benzoxazine-containing diterpenoid derivatives and subsequently developed an efficient synthetic platform for diverse analogues. The synthesized cyclopropyl- and cyclobutyl-substituted benzoxazine analogues demonstrate potent dual antibiofilm activity, simultaneously blocking biofilm formation and dismantling established biofilms.