title: Exploiting hidden symmetry in natural products: total syntheses of amphidinolides C and F.
abstract: The total synthesis of amphidinolide C and a second-generation synthesis of amphidinolide F have been accomplished through the use of a common intermediate to access both the C1-C8 and the C18-C25 sections. The development of a Ag-catalyzed cyclization of a propargyl benzoate diol is described to access both trans-tetrahydrofuran rings. The evolution of a Felkin-controlled, 2-lithio-1,3-dienyl addition strategy to incorporate C9-C11 diene as well as C8 stereocenter is detailed. Key controlling aspects in the sulfone alkylation/oxidative desulfurization to join the major subunits, including the exploration of the optimum masking group for the C18 carbonyl motif, are discussed. A Trost asymmetric alkynylation and a stereoselective cuprate addition to an alkynoate have been developed for the rapid construction of the C26-C34 subunit. A Tamura/Vedejs olefination to introduce the C26 side arm of amphidnolides C and F is employed. The late-stage incorporation of the C15, C18 diketone motif proved critical to the successful competition of the total syntheses.
authors.affiliation: Department of Chemistry, Oregon State University, Corvallis, Oregon 97331, USA.
authors.forename: Subham
authors.initials: S
authors.lastname: Mahapatra
authors.forename: Rich G
authors.initials: RG
authors.lastname: Carter
mesh_terms: D001565:Benzoates / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis*; D003500:Cyclization; D005663:Furans / Q000737:chemistry; D018942:Macrolides / Q000138:chemical synthesis*; D012834:Silver / Q000737:chemistry; D000097442:Amphidinolides
chemical_list: D001565:Benzoates; D001688:Biological Products; D005663:Furans; D018942:Macrolides; D012834:Silver; C429132:amphidinolide C; D000097442:Amphidinolides; C072156:amphidinolide F; C018674:tetrahydrofuran