title: A formal total synthesis of (+)-apicularen A: base-induced conversion of apicularen-derived intermediates into salicylihalamide-like products.
abstract: A synthesis of apicularen precursor (-)-6 in 18 steps from D-glucal is reported. As (+)-6 has been converted into the potent, naturally occurring salicylate anti-cancer agent, (-)-apicularen A in 8 steps, this study constitutes a formal total synthesis of (+)-apicularen A. Key steps in the synthetic route include: (i) useful D-glucal elaboration processes, (ii) organometallic displacements at carbohydrate C-6 triflates using Knochel-type and related functionalised, aromatic Grignard reagents, (iii) stereoselective allyltrimethylsilane-acetal reactions generating C-allyl systems, (iv) stereocontrolled aldehyde allylation processes from both substrate and reagent, and (v) a novel Keck-type macrolactonisation. In addition, preliminary studies are reported in which a procedure has been devised to convert apicularen-derived intermediates into salicylihalamide-like products.
authors.affiliation: Department of Chemistry, University of York, Heslington, York, UK YO10 5DD.
authors.forename: Arwel
authors.initials: A
authors.lastname: Lewis
authors.forename: Ian
authors.initials: I
authors.lastname: Stefanuti
authors.forename: Simon A
authors.initials: SA
authors.lastname: Swain
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Smith
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Taylor
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D002625:Chemistry, Organic / Q000379:methods; D008956:Models, Chemical; D011714:Pyrans / Q000737:chemistry
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D011714:Pyrans; C117813:apicularen A; C410986:salicylihalamide A