Total Synthesis of the Meroterpenoid Manginoid A as Fueled by a Challenging Pinacol Coupling and Bicycle‐forming Etherification

Abstract

The manginoids are a unique collection of bioactive natural products whose structures fuse an oxa-bridged spirocyclohexanedione with a heavily substituted trans-hydrindane framework. Herein, we show that such architectures can be accessed through a strategy combining a challenging pinacol coupling and bicycle-forming etherification with several additional chemo-and regioselective reactions. The success of these key events proved to be highly substrate and condition specific, affording insights for their application to other targets. As a result, not only has a 19-step total synthesis of manginoid A been achieved, but a potential roadmap to access other members of the family and related natural products has also been identified.

Combining the best of both worlds: radical-based divergent total synthesis

“…These classes exhibit diverse biological properties, such as potent inhibition of 11-βhydroxysteroid dehydrogenase type I and inhibition of Candida albicans [48]. Although earlier syntheses have been reported recently for magninoids [50,51], Lou's group envisioned a divergent plan based on a late-stage bioinspired semipinacol rearrangement-cyclization of common synthetic intermediates 94 and 95 (Scheme 8). Compound 94 was obtained in three steps, with the key step being the Suzuki-Miyaura coupling of appropriately functionalized precursors 91 and 92 using Romo and co-worker's protocol [52].…”

A Stereoselective Synthesis of Fused Carbocycles with a <i>cis</i>-1,2-Diol Moiety by Desymmetrization: SmI₂-Mediated Pinacol Coupling of <i>meso</i>-Cyclic 1,3-Diones

“…15,16) In particular, SmI 2 -mediated pinacol coupling [17][18][19][20][21][22][23][24][25] is a very useful reaction because it proceeds with high stereoselectivity under mild conditions to provide functionalized building blocks that are highly applicable to natural product synthesis. [26][27][28][29][30] Nevertheless, the application of intramolecular SmI 2 -mediated pinacol coupling of meso-cyclic 1,3-diones remains largely unexplored. 31) Herein, we describe the desymmetrization of meso-cyclic 1,3-diones bearing an all-carbon quaternary stereogenic center by SmI 2 -mediated pinacol coupling (Chart 1).…”

Enantioselective Total Syntheses of Manginoids A and C and Guignardones A and C

“…Yang group reported the first asymmetric total syntheses of ent ‐guignardones A and B from D‐quinic acid in 2020 [3c] . Recently, the first total synthesis of (±)‐manginoid A ( 1 ) was described by Snyder et al [3d] . Their elegant synthetic strategy involved challenging Pinacol coupling and bicycle‐forming etherification.…”