Biomimetic Synthesis of Meroterpenoids by Dearomatization‐Driven Polycyclization. Issue 45 (25th September 2019)

• Record Type: Journal Article
• Authors: Powers, Zachary; Scharf, Adam; Cheng, Andrea; Yang, Feng; Himmelbauer, Martin; Mitsuhashi, Takaaki; Barra, Lena; Taniguchi, Yoshimasa; Kikuchi, Takashi; Fujita, Makoto; Abe, Ikuro; Porco, John A.
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 45(2019)
• Page Start: 16141
• Page End: 16146
• Publication Date: 2019-09-25
• Subjects: 3, 5-dimethylorsellinic acid -- biosynthesis -- dearomatization -- meroterpenoids -- polyene cyclization; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201910710
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: A biomimetic route to farnesyl pyrophosphate and dimethyl orsellinic acid (DMOA)‐derived meroterpenoid scaffolds has yet to be reported despite great interest from the chemistry and biomedical research communities. A concise synthetic route with the potential to access DMOA‐derived meroterpenoids is highly desirable to create a library of related compounds. Herein, we report novel dearomatization methodology followed by polyene cyclization to access DMOA‐derived meroterpenoid frameworks in six steps from commercially available starting materials. Furthermore, several farnesyl alkene substrates were used to generate structurally novel, DMOA‐derived meroterpenoid derivatives. DFT calculations combined with experimentation provided a rationale for the observed thermodynamic distribution of polycyclization products. Abstract : Regioselective dearomatization of 3, 5‐dimethylorsellinic acid (DMOA) provides rapid access to a key dearomatized intermediate in the biosynthetic pathway of DMOA‐derived meroterpenoids. This intermediate undergoes polycyclization under Lewis acid mediation to provide meroterpenoid scaffolds. Several structurally novel meroterpenoids were obtained by termination via either C ‐ or O ‐cyclization.