Synthesis of Tryptanthrins by Organocatalytic and Substrate Co-catalyzed Photochemical Condensation of Indoles and Anthranilic Acids with Visible Light and O<sub>2</sub>

Li, Xiangmin; Huang, He; Yu, Chenguang; Zhang, Yueteng; Li, Hao; Wang, Wei

doi:10.1021/acs.orglett.6b03009

Cited by 36 publications

(24 citation statements)

References 44 publications

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“…A literature search using these data suggested the structure of tryptanthrin (1). [20] This assignment was unambiguously confirmed by direct comparison of all spectroscopic data with those of an authentic standard of tryptanthrin (1; purchased from Accela ChemBio Inc., San Diego, CA).…”

Section: Chemical Structure Determination Of Unknownmentioning

confidence: 74%

Ecological Roles of Tryptanthrin, Indirubin and N‐Formylanthranilic Acid in Isatis indigotica: Phytoalexins or Phytoanticipins?

Pedras

Abdoli

et al. 2019

Chemistry & Biodiversity

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Leaves of the plant species Isatis indigotica Fortune ex Lindl. (Chinese woad) produce the metabolites tryptanthrin, indirubin and N‐formylanthranilic acid upon spraying with an aqueous solution of copper chloride but not after spraying with water. The antifungal activities of these metabolites against the phytopathogens Alternaria brassicicola, Leptosphaeria maculans and Sclerotinia sclerotiorum established that tryptanthrin is a much stronger growth inhibitor of L. maculans than the phytoalexin camalexin. The biosynthetic precursors of tryptanthrin and N‐formylanthranilic acid are proposed based on the deuterium incorporations of isotopically labeled compounds. The overall results suggest that tryptanthrin is a phytoalexin and indirubin and N‐formylanthranilic acid are phytoanticipins in the plant species I. indigotica and that chemical diversity and biodiversity are intimately connected.

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Section: Chemical Structure Determination Of Unknownmentioning

confidence: 74%

Ecological Roles of Tryptanthrin, Indirubin and N‐Formylanthranilic Acid in Isatis indigotica: Phytoalexins or Phytoanticipins?

Pedras

Abdoli

et al. 2019

Chemistry & Biodiversity

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“…Anthranilate, renewable resource and simple biomass, is frequently used as biomimetic synthesis precursors . Previous endeavors using anthranilates to obtain indoloquinazolines are a few and only limited to tryptanthrin ( 10 ) . Furthermore, the synthesis of phaitanthrin E through the reaction of renewable resources has yet to be developed.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Phaitanthrin E and Tryptanthrin through Amination/Cyclization Cascade

Abe

Terasaki

2018

Helvetica Chimica Acta

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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.

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“…Three more publications have used indole (8) as starting material which is dimerized either with copper iodide as a catalyst under a continuous flux of oxygen 15 or via irradiation by LED light combined with the use of selected catalysts and simultaneous exposure to oxygen. 19,64 However, the developed synthetic protocol followed in our case seems to have certain advantages. This synthetic path is being described as an "eco-friendly olefin dihydroxylation" leading to the formation of vic diols from the corresponding alkenes.…”

Section: Discussionmentioning

confidence: 97%

“…The general method was followed using as starting material equivalent quantities of I3A 19 and are given in Supporting Information.…”

Section: Synthesis Of 6'-bromoindirubin (2h) and 3-bromotryptanthrin mentioning

confidence: 99%

A Biomimetic, One-Step Transformation of Simple Indolic Compounds to Malassezia-Related Alkaloids with High AhR Potency and Efficacy

Mexia

Koutrakis

et al. 2019

Chem. Res. Toxicol.

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Malassezia furfur isolates from diseased skin preferentially biosynthesize compounds which are among the most active known aryl-hydrocarbon receptor (AhR) inducers, such as indirubin, tryptanthrin, indolo[3,2-b]carbazole, and 6-formylindolo[3,2-b]carbazole. In our effort to study their production from Malassezia spp., we investigated the role of indole-3-carbaldehyde (I3A), the most abundant metabolite of Malassezia when grown on tryptophan agar, as a possible starting material for the biosynthesis of the alkaloids. Treatment of I3A with H2O2 and use of catalysts like diphenyldiselenide resulted in the simultaneous one-step transformation of I3A to indirubin and tryptanthrin in good yields. The same reaction was first applied on simple indole and then on substituted indoles and indole-3-carbaldehydes, leading to a series of mono- and bisubstituted indirubins and tryptanthrins bearing halogens, alkyl, or carbomethoxy groups. Afterward, they were evaluated for their AhR agonist activity in recombinant human and mouse hepatoma cell lines containing a stably transfected AhR-response luciferase reporter gene. Among them, 3,9-dibromotryptanthrin was found to be equipotent to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as an AhR agonist, and 3-bromotryptanthrin was 10-times more potent than TCDD in the human HG2L7.5c1 cell line. In contrast, 3,9-dibromotryptanthrin and 3-bromotryptanthrin were ∼4000 and >10,000 times less potent than TCDD in the mouse H1L7.5c3 cell line, respectively, demonstrating that they are species-specific AhR agonists. Involvement of the AhR in the action of 3-bromotryptanthrin was confirmed by the ability of the AhR antagonists CH223191 and SR1 to inhibit 3-bromotryptanthrin-dependent reporter gene induction in human HG2L7.5c1 cells. In conclusion, I3A can be the starting material used by Malassezia for the production of both indirubin and tryptanthrin through an oxidation mechanism, and modification of these compounds can produce some highly potent, efficacious and species-selective AhR agonists.

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Synthesis of Tryptanthrins by Organocatalytic and Substrate Co-catalyzed Photochemical Condensation of Indoles and Anthranilic Acids with Visible Light and O₂

Cited by 36 publications

References 44 publications

Ecological Roles of Tryptanthrin, Indirubin and N‐Formylanthranilic Acid in Isatis indigotica: Phytoalexins or Phytoanticipins?

Ecological Roles of Tryptanthrin, Indirubin and N‐Formylanthranilic Acid in Isatis indigotica: Phytoalexins or Phytoanticipins?

Synthesis of Phaitanthrin E and Tryptanthrin through Amination/Cyclization Cascade

A Biomimetic, One-Step Transformation of Simple Indolic Compounds to Malassezia-Related Alkaloids with High AhR Potency and Efficacy

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Synthesis of Tryptanthrins by Organocatalytic and Substrate Co-catalyzed Photochemical Condensation of Indoles and Anthranilic Acids with Visible Light and O2

Cited by 36 publications

References 44 publications

Ecological Roles of Tryptanthrin, Indirubin and N‐Formylanthranilic Acid in Isatis indigotica: Phytoalexins or Phytoanticipins?

Ecological Roles of Tryptanthrin, Indirubin and N‐Formylanthranilic Acid in Isatis indigotica: Phytoalexins or Phytoanticipins?

Synthesis of Phaitanthrin E and Tryptanthrin through Amination/Cyclization Cascade

A Biomimetic, One-Step Transformation of Simple Indolic Compounds to Malassezia-Related Alkaloids with High AhR Potency and Efficacy

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Product

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Synthesis of Tryptanthrins by Organocatalytic and Substrate Co-catalyzed Photochemical Condensation of Indoles and Anthranilic Acids with Visible Light and O₂