amphidinolide-c and tetrahydrofuran

An enantioselective synthesis of the C(1)-C(15) segment of the marine natural product amphidinolide C has been accomplished by a route that includes a stereoselective boron-Wittig reaction to furnish a trisubstituted alkenylboronate. In addition, the route employs enantioselective alkene diboration to install the C(6) hydroxyl group which undergoes intramolecular conjugate addition to establish a tetrahydrofuran ring. Lastly, a catalytic Suzuki-Miyaura cross-coupling is accomplished to construct the C(9)-C(10) bond.

Topics: Alkenes; Biological Products; Boron; Catalysis; Furans; Macrolides; Molecular Structure; Stereoisomerism

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.

Topics: Benzoates; Biological Products; Cyclization; Furans; Macrolides; Silver