Asymmetric Synthesis of ent-Fissistigmatin C

Abstract

The asymmetric synthesis of ent-fissistigmatin C is successively accomplished in 12 steps (longest linear sequence (LLS)). Relying on the enantioselective coupling of aliphatic aldehyde with 2-hydroxychalcone promoted by cooperative organocatalysts, the pivotal linkage of ent-fissistigmatin C between the flavonoid and the sesquiterpenoid fragment was stereoselectively established. An unprecedented final-stage radical cascade was also featured in this synthesis, which enabled the simultaneous establishment of the trans-decalin framework via forging two consecutive C–C bonds in one step.

Stereoselective Synthesis of Flavonoids: A Brief Overview

“…In addition, imidazolidinones were also relevant as chiral auxiliaries in the total synthesis of ent -fissistigmatin C. This molecule structure embodies a fragment of a flavonoid and another of the sesquiterpenoid linked through carbon 4 and carbon 1″, which establishes the generation of two stereogenic centres in the natural compound. Xu et al [ 86 ] developed a strategy to obtain fissistigmatin-C based on the reaction of a 2-hydroxychalcone and an aliphatic aldehyde [ 86 ]. In this reaction step, the flavonoid formed from the coupling of the two compounds previously mentioned was synthesised via a collaborative catalytic action of a chiral imidazolidine, ( R )-TRIP, and visible light ( Figure 17 ).…”

“…In this reaction step, the flavonoid formed from the coupling of the two compounds previously mentioned was synthesised via a collaborative catalytic action of a chiral imidazolidine, ( R )-TRIP, and visible light ( Figure 17 ). On the molecular level, ( R )-TRIP facilitated the attack of the enamine of the imidazolidinone in the si face by alleviating the steric hindrance, culminating with the formation of the flavonoid intermediate with 98% of the enantiomeric excess [ 86 ] ( Figure 17 ).…”

“… Stereoselective synthesis of flavonoid intermediate in ent-fissistigmatin-C synthesis (adapted from Xu et al) [ 86 ]. …”

Photoredox-Catalyzed Cascade Reactions Involving Aryl Radical: Total Synthesis of (±)-Norascyronone A and (±)-Eudesmol

“…Inspired by this key observation, an efficient route was designed for the synthesis of β-eudesmol. This sesquiterpenoid belongs to the eudesmane family that comprises over 1000 naturally occurring molecules, and their diverse structural types and wide range of biological activities have attracted extensive attention from the synthetic community . Starting from 12 , the selective reduction of the alkene double bond afforded the desired trans-fused decalin skeleton.…”

Convergent Synthesis of Enantioenriched ortho-Fused Tricyclic Diketones via Catalytic Asymmetric Intramolecular Vinylogous Aldol Condensation

“…In line with our continuous interest in terpenoid synthesis, we envisioned a convergent strategy for accessing enantioenriched ortho -fused tricyclic diketones based on the organocatalyzed asymmetric intramolecular vinylogous aldol reaction of enone 1 , which could be prepared via direct 1,6-Michael addition of cyclohexan-1,3-dione to 3-vinyl cyclic enone. As shown in Figure c, the chemoselective condensation of the enone moiety with the chiral primary amine catalyst led to dienamine En-1 via imine–enamine tautomerization.…”