Total synthesis of atropurpuran

• Published in: Nature communications Vol. 7; no. 1; p. 12183
• Main Authors: Gong, Jing, Chen, Huan, Liu, Xiao-Yu, Wang, Zhi-Xiu, Nie, Wei, Qin, Yong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.07.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 140/131; 639/638/403/937; Aldehydes; Aldehydes - chemistry; Alkaloids; Alkenes - chemistry; Biological Products - chemical synthesis; Chemical synthesis; Cyclization; Cycloaddition; Cycloaddition Reaction - methods; Diterpenes; Diterpenes - chemical synthesis; Humanities and Social Sciences; Hydroxyl groups; Laboratories; Molecular Structure; multidisciplinary; Natural products; Oxidation-Reduction; Phenols; Science; Science (multidisciplinary); Stereoisomerism; Stereoselectivity
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms12183

Due to their architectural intricacy and biological significance, the synthesis of polycyclic diterpenes and their biogenetically related alkaloids have been the subject of considerable interest over the last few decades, with progress including the impressive synthesis of several elusive targets. Despite tremendous efforts, conquering the unique structural types of this large natural product family remains a long-term challenge. The arcutane diterpenes and related alkaloids, bearing a congested tetracyclo[5.3.3.0 4,9 .0 4,12 ]tridecane unit, are included in these unsolved enigmas. Here we report a concise approach to the construction of the core structure of these molecules and the first total synthesis of (±)-atropurpuran. Pivotal features of the synthesis include an oxidative dearomatization/intramolecular Diels-Alder cycloaddition cascade, sequential aldol and ketyl-olefin cyclizations to assemble the highly caged framework, and a chemoselective and stereoselective reduction to install the requisite allylic hydroxyl group in the target molecule. Polycyclic and caged molecules are common in nature but present challenging targets for synthesis. Here, the authors report a route to caged diterpene cores and apply to the total synthesis of atropurpuran, with oxidative dearomatization/intramolecular Diels-Alder cascade, aldol and ketyl-olefin cyclizations as key steps.