Isolation, Synthesis, and Biological Activity of Quindoline, a Valuable­ Indoloquinoline Natural Product and Useful Key Intermediate­

Abstract

Quindoline is one of the simplest naturally occurring monomeric indoloquinoline alkaloids. Chemists exhibited interest in this compound before it was isolated from a natural source. The different approaches toward the total synthesis of the natural product and its performance in various biological tests are discussed. Aspects related to the isolation of quindoline from different ethnomedicinally relevant plants around the world are also reviewed.1 Introduction2 Isolation and Biogenetic Considerations3 Total Syntheses of Quindoline3.1 Early Synthetic Studies3.2 Syntheses from Benzenoids3.3 Syntheses from Indoles3.4 Syntheses from Quinolines4 Biological Activity Studies5 Conclusions

Copper‐Catalyzed Synthesis of 3‐NO2 Quinolines from o‐Azidobenzaldehyde and Nitro‐olefins and its Application in the Concise Synthesis of Quindolines

“…This method can be applied in the formal total synthesis of some important natural products, such as quindolines and cryptolepines (Figure ). Actually, there are mainly three approaches to obtain quindolines . The use of indoles as starting materials is fundamental to the synthesis of quindoline.…”

“…The use of indoles as starting materials is fundamental to the synthesis of quindoline. However, the diversity of strategies within this approach is rather limited . Another way which is started from halogen or amino substituted quinolines usually requires obtaining the coupled intermediates by noble metal (e. g., Pd) catalysts .…”

Efficient Buchwald–Hartwig and nitrene-mediated five-membered ring closure approaches to the total synthesis of quindoline. Unexpected direct conversion of a nitro group into a phosphazene

“…We have recently focused on the synthesis of indoloquinolines, 13 contributing with the total syntheses of quindoline ( 1 ) 14 and neocryptolepine ( 5 ). 15 Access to the unnatural 6-methylquinindoline ( 8a ) was also disclosed.…”

Synthesis of Fluorescent, DNA-Binding Benzo[b]indolonaphthyridinium Derivatives by a Misguided Westphal Condensation

“…The indoloquinolinium and indoloquinolizinium ions are promising structural motifs and lead structures in drug discovery. − These cationic azoniahetarenes are key structural features in various bioactive natural products such as javacarboline, flavopereirine, cryptolepine, and sempervirine, which have, for example, DNA-binding properties and antitumor activity. − In addition, the representatives of this class of compounds frequently exhibit a pronounced and characteristic fluorescence that changes significantly upon association with a biologically relevant host molecule, so that they may also be used for the fluorimetric detection of the latter. − As a result, the synthesis of indoloquinolinium and indoloquinolizinium derivatives is a topical research field in medicinal chemistry and pharmaceutical sciences, especially with the goal to identify highly bioactive and selective drug candidates. Among the synthetic approaches toward these target structures, cyclization reactions are often employed as essential key steps to assemble the azoniaheterocyclic framework. ,− For example, the conversion of benzenesulfonyl-protected 2-(pyridin-2-yl)­indoline derivatives, , the Stetter reaction, and the Sonogashira reaction in combination with the Larock indole synthesis have been successfully applied for this purpose.…”