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 sidearm 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.

Marine natural products

“…495 Amphidinolide C, a macrocyclic lactone metabolite of the dinoagellate Amphidinium sp., 496 has been synthesised through the use of a common intermediate to access both the C-1-C-8 and the C-18-C-25 sections. 497…”

Synthetic efforts on the road to marine natural products bearing 4-O-2,3,4,6-tetrasubstituted THPs: an update

“…In 2016, Carter and co-workers prepared the C1-C12 fragment of madeirolide A (5a) as a showcase of their silver catalyzed cyclisations to obtain THP. 158 The approach began with the Sonogashira coupling 67 between both known iodide 286 159 and alkyne 287 160 6.3 Lee's contribution (2016) 162 Lee and co-workers disclosed their approach towards the C1-C10 fragment of madeirolide A (5a). 162 Their approach involved the use of an Ir-catalysed visible light induced radical cyclisation to construct the THP ring and a Pd-catalysed glycosylation to assembly the saccharide fragment.…”

Bamford‐Stevens and Shapiro Reactions in Organic Synthesis

“…There are a couple of examples where Shapiro protocol failed, and the strategy had to be changed to complete the synthesis. The first example is from synthesis of amphidinolides [40] . Authors prepared 118 from a readily available starting material in four steps (scheme 23).…”