Total Synthesis of Zaragozic Acid C: Implementation of Photochemical C(sp3)–H Acylation

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• 作者：Takahiro Kawamata ; Masanori NagatomoMasayuki Inoue
• 刊名：Journal of the American Chemical Society
• 出版年：2017
• 出版时间：February 8, 2017
• 年：2017
• 卷：139
• 期：5
• 页码：1814-1817
• 全文大小：426K
• ISSN：1520-5126

文摘

Zaragozic acid C (1) was isolated as a potent squalene synthase inhibitor. The 2,8-dioxabicyclo[3.2.1]octane core of 1 is decorated with the three hydroxycarbonyl (C3,4,5), two hydroxy (C4,7), one acyloxy (C6), and one alkyl (C1) groups. Installation of the contiguous C4- and C5-fully substituted carbons presents a formidable synthetic challenge. Our approach to address this problem used a two-step photochemical C(sp³)–H acylation. Persilylated d-gluconolactone 4 was derivatized into 3 with the 1,2-diketone moiety at the C5-tetrasubstituted center. Norrish–Yang cyclization of 3 under violet LED irradiation followed by oxidative opening of the resultant α-hydroxycyclobutanone regio- and stereoselectively transformed the electron-rich tertiary C(sp³)–H bond at C4 into a C(sp³)–C bond to produce densely functionalized 2. A subsequent series of judicious functional group transformations gave rise to 1.