Total Synthesis of (±)-Aspergilline A

Abstract

The total synthesis of (±)-aspergilline A (1) is described. Key features of the synthesis include pyrrolinone formation via reaction of an intermediate propargyl amine with a methyl malonyl chloride derived ammonium enolate and a formal [3+2] cycloaddition between an imidate and cyclopropenone.

Cyclopropenones in the synthesis of indolizidine, pyrrolo[2,1-a]isoquinoline and indolizino[8,7-b]indole alkaloids

“…40 The reactions and literature observations shown in Table 2 confirm that cyclic ketimines react in the expected manner with cyclopropenones to give fused pyrrolidinones with no competing oxidations. We have shown previously that cyclic imidates and thioimidates 21,35 also react to give the expected products, a process was recently exploited by Nahkla and Wood 41 who used an imidate-cyclopropenone addition process as a key step in their synthesis of aspergilline A. We next used a known Bischler-Napieralski reaction of tryptamine to produce the dihydropyrido [3,4-b]indole 58 42 (Scheme 7), hence targeting the indolizinoindole nucleus after reaction with cyclopropenones.…”

A Ten‐Step Total Synthesis of Speradine C

“…To date, five total syntheses of the related but far less functionalized α‐CPA have been reported . However, of the highly oxygenated CPA‐derived alkaloids, only aspergilline A has succumbed to total synthesis . As part of our ongoing studies towards the concise and efficient synthesis of 3,4‐indole alkaloids, we are attracted by the intricate molecular architecture of the highly oxygenated CPA‐derived alkaloids.…”

A Ten‐Step Total Synthesis of Speradine C

“…To date, five total syntheses of the related but far less functionalized α‐CPA have been reported . However, of the highly oxygenated CPA‐derived alkaloids, only aspergilline A has succumbed to total synthesis . As part of our ongoing studies towards the concise and efficient synthesis of 3,4‐indole alkaloids, we are attracted by the intricate molecular architecture of the highly oxygenated CPA‐derived alkaloids.…”