title: Total synthesis of (-)-reidispongiolide A, an actin-targeting macrolide isolated from the marine sponge Reidispongia coerulea.
abstract: A stereocontrolled total synthesis of the microfilament-destabilizing cytotoxic macrolide (-)-reidispongiolide A, isolated from the New Caledonian marine sponge Reidispongia coerulea, is described. This synthesis utilizes a convergent aldol-based strategy to construct the 26-membered macrolactone, followed by the late-stage coupling of a derived aldehyde with an N-vinylformamide-containing ketone subunit to install the full side chain. Two alternative routes were examined for the introduction of the 2E,4E-dienoate region, and a complex Mukaiyama aldol coupling was used to connect the northern and southern hemispheres to install the C13 stereocenter. This constitutes the first chemical synthesis of any member of the reidispongiolide/sphinxolide family of marine macrolides and unequivocally establishes the relative and absolute configuration.
authors.affiliation: University Chemical Laboratory, Lensfield Road, Cambridge, CB2 1EW, UK. ip100@cam.ac.uk
authors.forename: Ian
authors.initials: I
authors.lastname: Paterson
authors.forename: Kate
authors.initials: K
authors.lastname: Ashton
authors.forename: Robert
authors.initials: R
authors.lastname: Britton
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cecere
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Chouraqui
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Florence
authors.forename: Henner
authors.initials: H
authors.lastname: Knust
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stafford
mesh_terms: D000199:Actins / Q000378:metabolism*; D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000199:Actins; D000447:Aldehydes; D007659:Ketones; D018942:Macrolides; C476919:reidispongiolide A; C116609:3-hydroxybutanal