First total synthesis of antiostatin A1, a potent carbazole-based naturally occurring antioxidant

Abstract

The first total synthesis of the potent antioxidant antiostatin A1 is reported, where its key features rely on a chemo- and regioselective rhodium-catalysed crossed alkyne cyclotrimerisation reaction applying functionalised ynamides and a palladium-catalysed arylamidation reaction.

[2+2+2] Cycloadditions of Alkynylynamides – A Total Synthesis of Perlolyrine and the First Total Synthesis of “Isoperlolyrine”

“…Alkynylynamide 8a [19] in THF solution was converted into the zinc derivative by deprotonation with LiHMDS followed by addition of anhydrous ZnBr 2 (Scheme 2). A Negishi coupling with tert-butyl 5-bromofuroate (9) [20] to TMS4a followed by TBAF-induced desilylation led to the desired diyne 4a in 79 % yield together with variable amounts of a byproduct 4c resulting from an intramolecular cyclization of 4a.…”

Ynamides: Versatile Tools in Organic Synthesis

“…A highly regioselective rhodium‐catalyzed cyclotrimerization then allowed for the formation of the carbazole core of antiostatin A 1 ( 189 ). The target molecule was obtained after functionalization of the carbazole 108…”

Ynamides: A Modern Functional Group for the New Millennium

“…Most recently, Witulski172 completed an elegant total synthesis of antiostatin A 1 (Scheme 178). As a key step, a chemo- and regioselective Rh-catalyzed alkyne cyclotrimerization reaction employing ynamide 717 afforded 719 in high yield through trapping of the rhodiacyclopentadiene intermediate 718 with an ynol ether.…”