Total Synthesis of Avrainvilleol

Abstract

The first total synthesis of the marine natural product avrainvilleol is reported. The total synthesis features the first application of the transition-metal-free coupling of a tosyl hydrazone and a boronic acid to the preparation of a complex natural product, and the first example of this coupling with a hindered diortho substituted hydrazone substrate.

Controlled Access to C1‐Symmetrical Cyclotriveratrylenes (CTVs) by Using a Sequential Barluenga Boronic Coupling (BBC) Approach

“…To set‐up our synthetic strategy, we choose to prepare a C 3 ‐symmetrical CTV, CTV‐3OMe 12 , known in the literature as the key intermediate in the synthesis of cryptophane‐111 (Scheme 2). [12,39] As mentioned by Miller et al ., [40] the steric hindrance of the boronic acid coupling partner in BBC can be deleterious for the reaction. A quick study of the substituents tolerated on the coupling partners (see supporting information) suggested that the coupling of hydrazone 5 and 3‐methoxyphenylboronic acid would give the best results.…”

Anticancer Activities of Marine-Derived Phenolic Compounds and Their Derivatives

“…Recently, extraction of another Avrainvillea species, A. amadelpha, resulted in the isolation of avrainvilleal (29) which exhibited moderate activity against HeLa cancer cells (IC 50 = 9.64 ± 1.7 µM) [147]. On the other side, Wegener and Miller reported the first total synthesis of avrainvilleol, a similar compound to 29, containing benzyl alcohol group [148].…”

Luxury of N‐Tosylhydrazones in Transition‐Metal‐Free Transformations

“…[21] Before attempting the synthesis of avrainvilleol, the authors tested the feasibility of the reactionw ith diortho-substituted hydrazones as well as boronica cids which clearly demonstratedt hat the hinderedh ydrazone was the perfect choicef or this methodology. [21] Before attempting the synthesis of avrainvilleol, the authors tested the feasibility of the reactionw ith diortho-substituted hydrazones as well as boronica cids which clearly demonstratedt hat the hinderedh ydrazone was the perfect choicef or this methodology.…”

“…Recently,t he first total synthesis of avrainvilleol 38, am arinen atural product,w as disclosed by Wegener and Miller based on the BBC strategy (Scheme13). [21] Before attempting the synthesis of avrainvilleol, the authors tested the feasibility of the reactionw ith diortho-substituted hydrazones as well as boronica cids which clearly demonstratedt hat the hinderedh ydrazone was the perfect choicef or this methodology. Then, the required boronic acid 37 was obtained from 4-methoxyphenylboronic acid throught hree steps.F or the hydrazone partner 39,t he corresponding aldehyde 36 was derived from vanillyl alcohol via four steps.…”

“…Recently, the first total synthesis of avrainvilleol 38 , a marine natural product, was disclosed by Wegener and Miller based on the BBC strategy (Scheme ) . Before attempting the synthesis of avrainvilleol, the authors tested the feasibility of the reaction with di‐ ortho ‐substituted hydrazones as well as boronic acids which clearly demonstrated that the hindered hydrazone was the perfect choice for this methodology.…”