Department of Chemistry and Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, United States.
Department of Chemistry and Department of Pharmacology and Chemical Biology, Emory University, Atlanta, Georgia 30322, United States.
J Am Chem Soc. 2023 Aug 30;145(34):18731-18736. doi: 10.1021/jacs.3c06031. Epub 2023 Aug 21.
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).
在此，我们报告了四个具有 6-7-5 三环骨架的哈美格兰天然产物的全合成。我们利用钯催化的分子内环丙醇开环交叉偶联反应构建了中环的七个环，以及一系列氧化反应，包括具有挑战性的芳基 C-H 氧化反应，以引入外围官能团。这种方法使我们能够首次完成哈美格兰 C（14 步）、去溴哈美格兰 I（12 步）和哈美格兰 I（13 步）的全合成。我们的合成还以 13 步得到了哈美格兰 G，这比以前报道的最短线性序列（24 步）要短得多。
