Concise Total Syntheses of the 6–7–5 Hamigeran Natural Products

• Type of Material: Article
• Authors: Baiyang Jian, Purdue University; Mingji Dai, Emory University
• Language: English
• Date: 2023-08-21
• Publisher: American Chemical Society
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1021%2Fjacs.3c06031
• Title of Journal or Parent Work: Journal of the American Chemical Society
• Volume: 145
• Issue: 34
• Start Page: 18731
• End Page: 18736
• Grant/Funding Information: This research was supported by NIH GM128570 and NSF 2102022.
• Keywords: chemical synthesis; ketones; pharmaceuticals; oxidation; organic synthesis
• Research Categories: Chemistry, Organic

Abstract

Herein, we report the total syntheses of four hamigeran natural products featuring a 6–7–5 tricyclic carbon skeleton. We utilized a palladium-catalyzed intramolecular cyclopropanol ring opening cross-coupling to build the central seven-membered ring and a series of oxidations including a challenging aromatic C–H oxidation to introduce the peripheral functionalities. This approach enabled us to achieve the first total syntheses of hamigeran C (14 steps), debromohamigeran I (12 steps), and hamigeran I (13 steps). Our synthesis also resulted in hamigeran G in 13 steps, which is significantly shorter than the previously reported one (24 steps, longest linear sequence).