Biomimetic Synthesis of Meroterpenoids by Dearomatization‐Driven Polycyclization. (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. Volume 131:Number 45(2019)
• Page Start: 16287
• Page End: 16292
• Publication Date: 2019-09-25
• Subjects: 3, 5-Dimethylorsellinsäure -- Biosynthese -- Dearomatisierung -- Meroterpenoide -- Polyen-Cyclisierung; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201910710
• Languages: English
• ISSNs: 0044-8249

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 : Die regioselektive Dearomatisierung von 3, 5‐Dimethylorsellinsäure (DMOA) ermöglicht einen schnellen Zugang zu einem dearomatisierten Schlüsselintermediat im Biosyntheseweg von DMOA‐basierten Meroterpenoiden. Das Zwischenprodukt geht eine Polycyclisierung in Gegenwart einer Lewis‐Säure ein, um Meroterpenoide zu liefern. Mehrere strukturell neuartige Meroterpenoide wurden durch Terminierung durch C ‐ oder O ‐Cyclisierung erhalten.