A General Approach to Indoles: Practical Applications for the Synthesis of Highly Functionalized Pharmacophores

Abstract

the development of a long-term manufacturing route to a potent and selective KDr kinase inhibitor has led to the discovery of several novel methodologies for the general synthesis of indoles. the key transformations involved addition of a trimethylsilylnitro benzene to an aromatic aldehyde which afforded the key nitroalcohol intermediate. oxidation of the nitroalcohol intermediate led to a nitroketone; whereas, elimination afforded exclusively a trans-nitrostyrene. reductive cyclization gave the target compounds in excellent overall yield from readily available bulk chemicals. Application of this methodology has led to the synthesis of highly functionalized pharmacophores including other KDr kinase inhibitors, biindoles and tjipanazole natural products, indolo[2,3-a]pyrrolo [3,4-c]carbazoles, indole-4-carboxylic amides, N-hydroxyindoles, and 2,3-dihydrobenzofurans.

Homo- and Heterodinuclear Complexes with Triazolyl-diylidene. An Easy Approach to Tandem Catalysts

“…As a model reaction we tested the consecutive cyclization of 2-aminophenyl ethyl alcohol (a reaction typically catalyzed by [Cp*IrCl 2 ] 2 ) and the alkylation of the resulting indole with a series of alcohols (catalyzed by Ir, Ru, and In compounds). Because indole-based compounds are found in many natural products with pharmaceutical applications, new environmentally benign and efficient methods for indole synthesis and its functionalization continue to attract attention . Although there is a large list of articles describing the alkylation of indoles with ketones and aldehydes, , the number of works in which alcohols are used instead is scarce and recent, and most respond to the development of new catalytic processes implying transition metal complexes. – , The one-pot tandem strategy to directly obtain alkylated indoles/bisindoles from the reaction of 2-aminophenyl ethyl alcohol and a series of alcohols (Scheme ) is a challenging process because it will allow us to compare the different activities of our dimetallic catalysts in two different and consecutive processes and may also provide some interesting insights into the design of efficient methods for the preparation of imidazolyl-based complexes with a wider set of functionalizations.…”

Bis- and Trisindolylmethanes (BIMs and TIMs)

“…These natural products have novel structures and exhibit a range of important biological activities. [9][10][11][12][13][14][15][16][17][18][19] Cancer chemotherapy with bis(3-indolyl)methane was recently reviewed and numerous activities are reported. 20 3,3′-Diindolylmethane and derivatives also are used as dietary supplements for humans.…”

Synthesis of Novel 4‐((Substituted bis‐indolyl)methyl)‐benzo‐15‐crown‐5 for the Colorimetric Detection of Hg2+ Ions in an Aqueous Medium

“…Much important bis-indole methane have been widely isolated from various terrestrial and marine natural sources. These natural products have novel structures and exhibit a wide range of biological activities [18][19][20][21][22][23][24][25][26][27]. Cancer chemotherapy with bis-(3-indolyl) methane was recently reviewed, and numerous activities have been reported [28].…”