Synthesis and biological evaluation of new penta- and heptacyclic indolo- and quinolinocarbazole ring systems obtained via Pd0 catalysed reductive N-heteroannulation

Abstract

A short route, involving a tetramolecular condensation reaction and a Pd/C catalyst-H(2)-mediated reductive N-heteroannulation as the key-steps, has been found for the synthesis of some new penta- and heptacyclic indolo- (12), quinolino- (13) and indoloquinolinocarbazole (11) derivatives. HF-DFT (B3LYP) energy profiles and NMR calculations were carried out to help in the understanding of the experimental results. N-Alkylated indoloquinolinocarbazoles (16b, 17a, 17b and 18) were prepared and screened essentially toward some cancer-(G-quadruplex, DNA, topoisomerase I) and CNS-related (kinases) targets. Biological results evidenced 13 as a potent CDK-5 and GSK-3β kinases inhibitor, while di- or triaminopropyl-substituted indoloquinolinocarbazoles 17b or 18 targeted rather DNA-duplex or telomeric G-quadruplex structures, respectively.

Chemistry and Properties of Indolocarbazoles

“…280 In this context, it is also worth mentioning that a single example of an indolo[3,2-b]carbazole has been reported as a minor product in low yield from a conceptually related palladium-catalyzed reductive cyclization of a nitroaromatic precursor in the presence of hydrogen. 281 An extensive set of extended indolo[3,2-b]carbazoles obtained using a sequence involving double Suzuki and Cadogan reactions has been reported. In a representative example, the coupling of the carbazole 274 with phenylboronic acid, followed by cyclization of the resulting intermediate 275 under microwave-assisted Cadogan conditions, provided the product 276 in respectable yield (Scheme 60).…”

Cover Picture: Exploring the Potential Energy Surface of E2P4 Clusters (E=Group 13 Element): The Quest for Inverse Carbon‐Free Sandwiches (Chem. Eur. J. 16/2014)

“…Furthermore, one‐pot access to biologically attractive10 pentacyclic quinolinone‐fused carbazole derivative 14 was obtained in an excellent 97 % yield from 4abn by a reductive cyclolactamization sequence process using Pd/C/NH 4 HCO 2 as a mild reducing system (Scheme ).…”

Catalytic Methods for Aromatic C–H Amination: An Ideal Strategy for Nitrogen-Based Functional Molecules

“…Nitroarenes and nitroalkenes have proven to be a good precursor of nitrenes in the presence of metal catalyst under reductive CO ,, or H 2 atmosphere. In 2009, Dong reported palladium-catalyzed synthesis of indoles under CO atmosphere (Scheme ).…”