title: Synthesis of the C19 methyl ether of aspercyclide A via germyl-Stille macrocyclisation and ELISA evaluation of both enantiomers following optical resolution.
abstract: Aspercyclide A (1) is a biaryl ether containing 11-membered macrocyclic natural product antagonist of the human IgE-FcεRI protein-protein interaction (PPI); a key interaction in the signal transduction pathway for allergic disorders such as asthma. Herein we report a novel approach to the synthesis of the C19 methyl ether of aspercyclide A, employing a Pd(0)-catalysed, fluorous-tagged alkenylgermane/arylbromide macrocyclisation (germyl-Stille reaction) as the key step, and evaluation of both enantiomers of this compound via ELISA following optical resolution by CSP-HPLC. A crystal structure for germyl hydride 27 is also reported.
authors.affiliation: Department of Chemistry, South Kensington campus, Imperial College, London, UK SW7 2AZ.
authors.forename: James L
authors.initials: JL
authors.lastname: Carr
authors.forename: Jimmy J P
authors.initials: JJ
authors.lastname: Sejberg
authors.forename: Fabienne
authors.initials: F
authors.lastname: Saab
authors.forename: Mary D
authors.initials: MD
authors.lastname: Holdom
authors.forename: Anna M
authors.initials: AM
authors.lastname: Davies
authors.forename: Andrew J P
authors.initials: AJ
authors.lastname: White
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Leatherbarrow
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Beavil
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Sutton
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Lindell
authors.forename: Alan C
authors.initials: AC
authors.lastname: Spivey
mesh_terms: D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D003500:Cyclization; D004797:Enzyme-Linked Immunosorbent Assay; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D008738:Methyl Ethers / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D007783:Lactones; D047028:Macrocyclic Compounds; D008738:Methyl Ethers; C542833:aspercyclide A