Total Synthesis of the Diterpenoid Alkaloid Arcutinidine Using a Strategy Inspired by Chemical Network Analysis.

ABSTRACT: Arcutinidine and other arcutinidine-type diterpenoid alkaloids feature an intricate polycyclic, bridged framework with unusual connectivity. A chemical network analysis approach to the arcutane skeleton enabled the identification of highly simplifying retrosynthetic disconnections, which indicated that the caged structure could arise from a simpler fused ring system. On this basis, a total synthesis of arcutinidine is reported herein, featuring an unprecedented oxopyrrolium Diels-Alder cycloaddition which furnishes a key tetracyclic intermediate. In addition, the synthesis utilizes a diastereoselective oxidative dearomatization/cycloaddition sequence and a SmI₂-mediated C-C coupling to forge the bridged framework of the natural products. This synthetic plan may also enable futur

SUBMITTER: Owens KR 

PROVIDER: S-EPMC7771644 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature