Synthesis of Indole Derivatives with Biological Activity by Reactions Between Unsaturated Hydrocarbons and N-Aromatic Precursors

Giovanni      Palmisano; Andrea      Penoni; Massimo      Sisti; Francesco      Tibiletti; Stefano      Tollari; Kenneth      M. Nicholas

doi:10.2174/138527210793358277

Abstract

The present review is devoted to illustrate the state of the art of the syntheses of indoles, focusing particularly on the most recent developments of new synthetic approaches. Emphasis is given to the preparation of natural products or bioactive compounds containing the indole unit. We present a historical perspective of indole synthesis showing the strategies by choosing the nitrogen precursors. The review is organized sharing the indole synthetic approaches by using different nitrogen-containing functional groups in aromatic substrates used as source of the nitrogen of the indole moiety. Some functional groups and some typical reactions are particularly stressed and highlighted because of the limited coverage given in previous reviews published on this topic. Other synthetic approaches more used and discussed in recent, complete and excellent reviews on the topic are summarized but the most recent published results are highlighted. Our interest is particularly focused on the indolization procedures and on the different methods used for the ring closure and no attention is given to modification of indole structures starting from molecules with a preformed indole unit. Intriguing indole syntheses are continually discovered and the importance that the scientific community gives to these new developments is connected with the strategic role of molecules containing the indole unit. Indoles are the class of heterocycles with more applications and extensive interest due to their biological and pharmacological activity.

Keywords: Indoles, natural products, bioactive compounds, heterocyclic synthesis, annulations, nitrogen-containing functional groups, named reactions, alkaloids, N-heterocycles, indole-3-acetic, indole-3-butyric, Anilines-Amines, Anilides-Amides, o-Aminobenzaldehydes, Evodia rutaecarpa, o-acylanilines, α-arylaminocarbonyl compounds, N-diacylanilines, 2-Alkynylarylamines, fuchsiaefoline, 3-(α-trifluoroacetamidoaryl)-1-propargylic esters, o-Chloroarylamines, N-alkylindoles, N-alkylazaindoles, copper-free Sonogashira alkynylation, o-Halo-N-arylenamines, o-halo-N-vinylamines, N-propargylamines, N-allylamines, N-Vinyl-o-haloanilines, 5-hydroxyindole-3-carboxamides, 3-indolecarbonitriles, FeCl3, •, 6H2O-NaI system, Kirkpatrickia varialosa, N-aryl-O-vinylhydroxylamino magnesium salt, phenylacetylene 1,3'-diepoxy-3,3'-diphenyl-2,2'-bi-indolinyl, Aplidium meridianum, Arylhydroxylamines, Nacylbenzotriazoles