title: Synthesis of antimicrofilament marine macrolides: synthesis and configurational assignment of a C5-C16 degradation fragment of reidispongiolide A.
abstract: Reidispongiolide A is a representative member of the sphinxolide/reidispongiolide group of cytotoxic 26-membered macrolides of marine origin. By interacting with actin in the cell cytoskeleton, the reidispongiolides and sphinxolides are potent microfilament destabilizing agents that represent a promising mechanism of action for developing novel anticancer drugs. An aldol-based synthesis of a library of diastereomers of C(8)-C(16) and C(5)-C(16) fragments and detailed NMR comparison with a reported degradation fragment enabled a configurational assignment for a major part of the reidispongiolide macrocyclic core, thus setting a solid foundation for ongoing synthetic efforts.
authors.affiliation: University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, United Kingdom. ip100@cam.ac.uk
authors.forename: Ian
authors.initials: I
authors.lastname: Paterson
authors.forename: Robert
authors.initials: R
authors.lastname: Britton
authors.forename: Kate
authors.initials: K
authors.lastname: Ashton
authors.forename: Henner
authors.initials: H
authors.lastname: Knust
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stafford
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects; D002625:Chemistry, Organic / Q000379:methods; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D008386:Marine Biology; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism
chemical_list: D007659:Ketones; D018942:Macrolides; C476919:reidispongiolide A