title: Bio-inspired formal synthesis of hirsutellones A-C featuring an electrophilic cyclization triggered by remote Lewis acid-activation.
abstract: A bio-inspired strategy was used to complete the formal synthesis of the antitubercular hirsutellone B and congeners A and C, through construction of its decahydrofluorene core from a linear polyene strand activated at both ends by a silyl enol ether and an allyl acetate. Our synthesis features a key electrophilic cyclization, starting with the remote activation (by [Yb(OTf)3] or BF3·OEt2) of the allyl acetate and stereoselectively affording the C ring. This was followed by an intramolecular Diels-Alder reaction to get the tricyclic core of the natural product. The stereoselective reduction of the resulting ketone towards the formal intermediate was critical to the success of this strategy.
authors.affiliation: Muséum National d'Histoire Naturelle, 57 rue Cuvier (CP 54), 75005 Paris (France); CNRS, UMR 7245, Unité Molécules de Communication et Adaptation des Micro-organismes, Paris (France).
authors.forename: Xu-Wen
authors.initials: XW
authors.lastname: Li
authors.forename: Alexandre
authors.initials: A
authors.lastname: Ear
authors.forename: Lukas
authors.initials: L
authors.lastname: Roger
authors.forename: Nassima
authors.initials: N
authors.lastname: Riache
authors.forename: Alexandre
authors.initials: A
authors.lastname: Deville
authors.forename: Bastien
authors.initials: B
authors.lastname: Nay
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003500:Cyclization; D061565:Cycloaddition Reaction; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006999:Hypocreales / Q000737:chemistry; D007659:Ketones / Q000737:chemistry; D058116:Lewis Acids / Q000737:chemistry*; D015394:Molecular Structure
chemical_list: D000995:Antitubercular Agents; D001688:Biological Products; D006576:Heterocyclic Compounds, 4 or More Rings; D007659:Ketones; D058116:Lewis Acids; C568588:hirsutellone A; C545159:hirsutellone B; C568589:hirsutellone C
keywords: Lewis acids; biomimetic synthesis; electrophilic cyclization; natural products; synthetic methods