Gold(I)-Catalyzed 7-exo-dig Cyclization: A Key Step to Access the Bicyclo[4.2.1]nonane Skeleton of Vibsatin A, a Neurotrophic Diterpenoid

Abstract

Vibsatin A is a new neurotrophic vibsane-type diterpenoid comprising a bridged bicyclo[4.2.1]­nonane skeleton. Inspired by Sawamura’s works, we generated the bicyclic backbone through a Conia-ene-derived 7-exo-dig cyclization from an enantiomerically enriched TIPS-based silyl enol ether. The reaction, catalyzed by a sensitive gold­(I) complex, was efficiently performed on a large scale by glovebox free techniques. Furthermore, the shape of this system was exploited for subsequent installation of all of the stereogenic centers.

Discovery of the Caged-Vibsane Norditerpenoids with Unprecedented Chemical Architectures and Exploration of Their Various Acid Tolerances

“…Vibsane-type diterpenes (VibDs) have been regarded as a type of unusual diterpene that occurs exclusively in only six species of the genus Viburnum (Adoxaceae) to date. Their intriguing polytropic structures and prominent antitumor properties have sparked the interest of natural medicinal chemists and pharmacologists, − leading to a series of successful total syntheses of VibDs. − Conventionally, VibDs are categorized into three subtypes with 11-membered, seven-membered, and rearranged ring types. Eleven-membered VibDs feature a humulane skeleton with an isopentenyl unit at C-11, which is considered as the common biosynthetic precursor of all VibDs.…”

Vibsanoids A–D, four new subtypes of vibsane diterpenoids with a distinctive tricyclo[8.2.1.02,9]tridecane core fromViburnum odoratissimum

“…6 Previous studies have revealed that VibDs exert significant neurotrophic and cytotoxic bioactivities, some of which have aroused extensive attention. 7–10…”

“…6 Previous studies have revealed that VibDs exert significant neurotrophic and cytotoxic bioactivities, some of which have aroused extensive attention. [7][8][9][10] Viburnum odoratissimum, a landscape plant rich in VibDs, is widely distributed in many provinces of China. 11,12 In the process of continuous study on this plant, it was discovered that the molecular weights of most of the VibDs were between 400 and 500, and the MS/MS spectra of VibDs in our database showed a characteristic β,β-dimethyl acryl substituent fragment ion at C-8 (m/z 83).…”