Construction of the Hexacyclic Core of Dispirocochlearoids A—C via a Diels−Alder Reaction

Abstract

Comprehensive Summary The natural products of dispirocochlearoids are complex Ganoderma meroterpenoids featuring a 6/6/5/6/6/6 ring system and are selective COX‐2 inhibitors. Herein, we describe our progress regarding the total synthesis of dispirocochlearoids A—C, in which a hexacyclic skeleton was constructed firstly. The key steps of this work involve an intermolecular [4 + 2] cycloaddition reaction, a ring cleavage approach via TiCl4, and the installation of a profoundly sterically hindering lactone.

Insights into Ganoderma fungi meroterpenoids opening a new era of racemic natural products in mushrooms

“…38 (±)-Applanatumols V, W, and Z (141-146) possessing a five-membered ring attached at the benzyl ketone carbonyl were characterized from G. applanatum. 38 Investigation of G. applanatum also resulted in the isolation of their derivatives, (±)-applanatumols X, Y, and Z2 (147)(148)(149)(150)(151)(152), comprising a chromone backbone formed by the phenol hydroxyl and the carbon on the five-membered ring, and applanatumol Z1 (153) whose five-membered ring fractured. 38 Structurally similar racemate of applanatumol Z1 named (±)-ganodercin T (154 and 155) was generated from G. cochlear.…”

“…63 And in 2020, the Jiang group achieved it in 5 steps, with 57.6% yield via condensation reaction. 146 148 And the Lan group reported the first total syntheses of lucidimines B and C (658 and 665). 121…”

Structural diversity, hypothetical biosynthesis, chemical synthesis, and biological activity ofGanodermameroterpenoids

“…In vivo , dispirocochlearoid B also showed anti-inflammatory activities in an acute lung injury (ALI) mouse model, which attracted Nan's attention and they reported a synthetic strategy to construct the core skeleton via a Diels–Alder reaction. 108…”

“…The following reduction, deprotection, oxidative cyclization, and cleavage of the silyl ester afforded 283 containing the desired hexacyclic core (Scheme 14). 108…”

“…In vivo, dispirocochlearoid B also showed anti-inammatory activities in an acute lung injury (ALI) mouse model, which attracted Nan's attention and they reported a synthetic strategy to construct the core skeleton via a Diels-Alder reaction. 108 Scheme 2 Total synthesis of (±)-lingzhiol (3) by Maier and coworkers. 87 In the following construction of the a,bunsaturated g-lactone, the methylation-protected 279 was changed to triisopropylsilyl ether 280.…”