title: Synthesis of polyprenylated acylphloroglucinols using bridgehead lithiation: the total synthesis of racemic clusianone and a formal synthesis of racemic garsubellin A.
abstract: The synthesis of polyprenylated phloroglucinol natural products, including clusianone, nemorosone, and garsubellin A, was pursued by a strategy involving construction of a core bicyclo[3.3.1]nonanetrione structure and subsequent elaboration via organolithium intermediates. Appropriate bridged core structures were obtained through the cyclization of a suitably substituted cyclohexanone enol ether or enol silane with malonyl dichloride. Additional substituents were then introduced by means of regioselective lithiation reactions, including the generation of bridgehead enolates, thus enabling the total synthesis of clusianone and also of an advanced intermediate toward nemorosone. In the case of garsubellin A, an additional THF-like ring was elaborated by a biomimetic 5-exo-tet cyclization of an enol ether (or enol) with a side-chain epoxide. This enabled a formal synthesis of racemic garsubellin A by accessing one of the late intermediates in the Danishefsky synthesis.
authors.affiliation: School of Chemistry, The University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: Nadia M
authors.initials: NM
authors.lastname: Ahmad
authors.forename: Vincent
authors.initials: V
authors.lastname: Rodeschini
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Simpkins
authors.forename: Simon E
authors.initials: SE
authors.lastname: Ward
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Blake
mesh_terms: D000215:Acylation; D000478:Alkylation; D001577:Benzophenones; D016227:Benzoquinones; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002713:Chlorine / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D003500:Cyclization; D004986:Ether / Q000737:chemistry; D015394:Molecular Structure; D009387:Neoprene / Q000737:chemistry*; D010696:Phloroglucinol / Q000737:chemistry*; D012821:Silanes / Q000737:chemistry; D013237:Stereoisomerism; D013729:Terpenes / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C118110:7-epiclusianone; D001577:Benzophenones; D016227:Benzoquinones; D001643:Bridged Bicyclo Compounds; D012821:Silanes; D013729:Terpenes; C106690:garsubellin A; C016077:prenyl; D004986:Ether; D002713:Chlorine; D003300:Copper; D009387:Neoprene; D010696:Phloroglucinol