Synthesis of Phaitanthrin E and Tryptanthrin through Amination/Cyclization Cascade

Abstract

Phaitanthrin E was biomimetically synthesized from methyl indole‐3‐carboxylate and methyl anthranilate or anthranilic acid using the ester group as an activating group. The reaction proceeds through NCS‐mediated dearomatization/TFA‐catalyzed protonation of indolenine/C(2) amination/Et3N‐promoted aromatization and cyclization in one‐pot procedure. This method is capable of converting simple biomass materials to phaitanthrin E. The synthesis not only allows assessment of antiproliferative activity, but also affords experimental support for the hypothetical biosynthetic pathway of phaitanthrin E. The resulting phaitanthrin E derivatives were evaluated for in vitro antiproliferative activity against human colorectal cancer cells (DLD‐1). The biogenetic intermediate of phaitanthrin E showed higher antiproliferative activity than the natural product, phaitanthrin E. Furthermore, a concise synthesis of tryptanthrin is also accomplished from indole‐3‐carbaldehyde and methyl anthranilate using the aldehyde group as an activating group.

Double “Open and Shut” Transformation of γ-Carbolines Triggered by Ammonium Salts: One-Pot Synthesis of Multiheterocyclic Compounds

“…During the studies on 1 , we envisaged a cascade reaction between in situ generated indolenines derived from 1 and γ-carbolines 2 via a Hofmann elimination followed by vinylogous Mannich/retro-Mannich/cyclization triggered by another γ-carbolines 2 to afford the multiheterocyclic compounds 3 (Scheme c). Based on our ongoing research into the synthesis of heterocycles and the aforementioned reactivity of γ-carbolines (Scheme a,b), we herein report a novel cascade sequence starting from indole 2,3-epoxide equivalents as electrophiles and γ-carbolines as nucleophiles that furnished difficult-to-access multiheterocyclic compounds.…”

Tryptanthrin and Its Derivatives in Drug Discovery: Synthetic Insights

“…Decarbonylation and further oxidation leads to the formation of the final product, tryptanthrin. 33 In another example of the use of molecular iodine for the synthesis of tryptanthrin, Guo et al reported a cascade reaction involving 2′-bromoacetophenones (10) and 2-aminobenzamides (11) as substrates. Molecular iodine promotes the oxidation of the 2′-bromoacetophenone to intermediate 12, which, through cyclocondensation with 11 in the presence of CuBr and a base, affords intermediate 13, which undergoes an intramolecular Ullmann amidation to afford tryptanthrin (71% yield) and its derivatives (10 examples, 41-75% yield; Scheme 7).…”

Synthesis of indole derivatives as prevalent moieties present in selected alkaloids

“…Among the various acids, propionic acid was the most effective acid at providing the desired cyclized products (88% yield, 187/ 188 ¼ 33 : 67) (Scheme 24). 221 The Tabernaemontana genus belongs to the family Apocynaceae containing various species distributed throughout subtropical and tropical regions of the world, including Brazil. 222 (AE)-Minovincine was extracted from Tabernaemontana riedelii by Szántay in 1997.…”

“…started from the reaction of tert-butyl 3-oxopent-4-enoate (221) and methyl 5-chloro-2-formylpentanoate (222), that afforded 1,3-dicarboxylate 223. The latter, aer three steps, gave the stereochemically complex intermediate 225.…”