Total Synthesis of Zaragozic Acid C: Implementation of Photochemical C(sp3)–H Acylation
| Autor: | Masayuki Inoue, Takahiro Kawamata, Masanori Nagatomo |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
chemistry.chemical_classification
010405 organic chemistry Stereochemistry Zaragozic acid C Total synthesis General Chemistry 010402 general chemistry Photochemistry 01 natural sciences Biochemistry Catalysis 0104 chemical sciences Acylation chemistry.chemical_compound Squalene Colloid and Surface Chemistry chemistry Functional group Moiety Alkyl Octane |
| Zdroj: | Journal of the American Chemical Society. 139:1814-1817 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/jacs.6b13263 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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