title: Total synthesis of clostrubin.
abstract: Clostrubin is a potent antibiotic against methicillin- and vancomycin-resistant bacteria that was isolated from a strictly anaerobic bacterium Clostridium beijerinckii in 2014. This polyphenol possesses a fully substituted arene moiety on its pentacyclic scaffold, which poses a considerable challenge for chemical synthesis. Here we report the first total synthesis of clostrubin in nine steps (the longest linear sequence). A desymmetrization strategy is exploited based on the inherent structural feature of the natural product. Barton-Kellogg olefination forges the two segments together to form a tetrasubstituted alkene. A photo-induced 6π electrocyclization followed by spontaneous aromatization constructs the hexasubstituted B ring at a late stage. In total, 200 mg of clostrubin are delivered through this approach.
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Collaborative Innovation Center of Chemistry for Life Sciences, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Collaborative Innovation Center of Chemistry for Life Sciences, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Collaborative Innovation Center of Chemistry for Life Sciences, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
authors.forename: Ang
authors.initials: A
authors.lastname: Li
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D000693:Anaerobiosis; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D046970:Clostridium beijerinckii / Q000737:chemistry / Q000378:metabolism; D003500:Cyclization; D008027:Light; D055668:Photochemical Processes; D011084:Polycyclic Aromatic Hydrocarbons / Q000138:chemical synthesis*; D061065:Polyketides / Q000138:chemical synthesis*; D059808:Polyphenols / Q000138:chemical synthesis*
chemical_list: D000475:Alkenes; D000900:Anti-Bacterial Agents; D011084:Polycyclic Aromatic Hydrocarbons; D061065:Polyketides; D059808:Polyphenols; C000604643:clostrubin