Total Synthesis of Luotonin A and Rutaecarpine from an Aldimine via the Designed Cyclization

Abstract

The total synthesis of rutaecarpine (1) and luotonin A (2) is described through controlled cyclization of a common aldimine intermediate 5 derived from ethyl-2-aminocinnamate and quinazolinone-2-carbaldehyde. The cyanide-mediated imino-Stetter reaction of aldimine 5 provided the corresponding indole derivative 3, from which the total synthesis of rutaecarpine (1) was completed via the formation of a 6-membered C-ring. On the other hand, microwave-assisted thermal 6π-electrocyclization of the common intermediate 5, followed by the formation of a 5-membered C'-ring, allowed the completion of the total synthesis of luotonin A (2).

tert‐Butoxide‐Mediated Synthesis of 3,4′‐Biquinolines from 2‐Aminochalcones

“…Our group has commenced a research program to develop novel protocols to access quinoline derivatives from readily available starting materials . In this regard, we recently developed highly efficient protocols for the synthesis of 2‐substituted quinolines 2 from 2‐aminochalcones 1 using a nucleophile as the catalyst (Scheme a).…”

Recent Advances in Stetter Reaction and Related Chemistry: An update

“…Therefore, total synthesis of rutaecarpine 285 was accomplished from the known starting precursors in just four steps with a moderate overall yield (38% yield) (Scheme 66). [138] The indoloquinolizine moiety is a usual framework that is found in biologically significant naturally occurring compounds and pharmaceuticals for example arborescidine A 290 and nauclefidine 291. Thus, the establishment of unique methods to obtain these framework has been obtained much attention.…”

“…Several important scaffolds present in natural products can easily be provided via Stetter reaction. They are quinazolinone 239 , [87f] 5,8‐methanobenzo[7]annulen‐9‐one 240 [94] indoloquinolizine 241 , [87c] indolo[3,2‐ j ]phenanthridine 242 , indolocarbazole 244 [87d] and ketosuccinimide 243 [32] (Figure 2).…”

“…Therefore, total synthesis of rutaecarpine 285 was accomplished from the known starting precursors in just four steps with a moderate overall yield (38% yield) (Scheme 66). [138] …”

Chemistry of Cyanide Adducts of Aldimines from Aniline Derivatives

“…Considering their structural similarities, we envisaged that rutaecarpine ( 33 ) and luotonin A ( 34 ) could be prepared from the same aldimine intermediate 36 , obtained from ethyl 2‐aminocinnamate ( 26 a ) and quinazolinone‐2‐carboxaldehyde ( 35 ) if the controlled formation of heterofused B,C‐ and B′,C′‐ring systems in each respective natural product were possible thereafter (Scheme ) …”