Total Synthesis of (±)-Spiroaxillarone A

Abstract

Spiroaxillarone A, a novel and unique spirocyclic dinaphthalene natural product with significant antimalarial activity, was regioselectively synthesized from tetrahydrocurcumin in five steps with an overall 10% yield. Key features of the synthesis involved an oxidized free radical cycloaddition to build the spiro ring central skeleton and an oxidized dehydrogenation to introduce two double bonds via enol silicon ether from diketones.

Spirobisnaphthalenes from Fungi, Biological activities and Total Synthesis: A Research Review

“…Until now, three routes for the total synthesis of racemic spiroaxillarione A have been reported. The first route (Scheme 15) was a biomimetic pathway by Xie's group [55] . In this strategy, the spiro quaternary carbon center was constructed through a key Mn(OAc) 3 ‐mediated oxidative free‐radical cycloaddition from the intermediate 15 ‐ 2 , which was derived from tetrahydrocurcumin 15 ‐ 1 .…”

Total Synthesis of (±)-Spiroaxillarone A via a Reversible Sulfa-Michael Addition

“…Because of its unique structural feature and important antimalarial activity, spiroaxillarone A attracted attention from the synthetic community including our group. Early this year, Xie and co-workers reported an elegant biomimetic synthetic route to spiroaxillarone A through a Mn­(OAc) 3 -mediated free-radical cyclization . As one of our continuous efforts to design synthetic route under the inspiration of biosynthetic pathway, here we report a de novo route to the synthesis of spiroaxillarone A …”

Synthesis of Seleno-Dibenzocycloheptenones/Spiro[5.5]Trienones by Radical Cyclization of Biaryl Ynones

“…Likewise, spirocyclic scaffolds are frequently found in nature and have important applications in medicinal chemistry . Spiroaxillarone A ( F ), a spiro[5.5]­undecane skeleton, for example, was isolated from Cyanotis axillaris , and its derivatives exhibited significant antimalarial activity against resistant Plasmodium falciparum (Figure ). Other bioactive natural products with this skeleton are Pulchelstyrene D ( G ), from Phyllodium pulchellum ; Laurencenone C ( H ), a member of the abundant sesquiterpenoid family known as chamigrenes, isolated from the alga of the genus Laurencia obtuse ; and Majusculone ( I ), a naturally occurring 9-norchamigrene-type metabolite that was first isolated from red algae Laurencia majuscule Harvey (Figure ).…”