γ-Carbolines and their hydrogenated derivatives 3.* Hydrogenated derivatives of γ-carbolines: chemical and biological poperties (Review)

Abstract

Published data on the chemical transformations and biological properties of dihydro-, tetrahydro-, and hexahydro-γ-carbolines are reviewed.

Double “Open and Shut” Transformation of γ-Carbolines Triggered by Ammonium Salts: One-Pot Synthesis of Multiheterocyclic Compounds

“…Based on the above results and the literature precedents, ,,− a plausible reaction pathway for this cascade sequence is depicted in Scheme . At first, the ammonium exchange of 1a by 2a via the indole 2,3-epoxide 4 affords the bulky ammonium salt 5 with the release of Et 3 N. Upon Hofmann elimination assisted by Et 3 N, 5 is converted to the indolenium salt 6 , which may increase the electrophilicity of the benzylic position of isotryptamine .…”

“…These involve retro-Mannich/cyclization of γ-carbolines, Mannich-type reaction, Pd-catalyzed cyclocarbonylation, Ullmann N -arylation/oxidative C–H amination, diamination/oxidative cross-coupling/bicyclization, Pd-catalyzed asymmetric dearomative cyclization, and the reaction of 2-bromomethylazoles and isocyanides . Among these strategies, the retro-Mannich/cyclization of γ-carbolines is thought to be the most concise methodology for the synthesis of pyrimido­[1,6- a ]­indoles . This reaction proceeds by initial halogenation of the γ-carboline, which then undergoes retro-Mannich fragmentation followed by recyclization to afford the pyrimido­[1,6- a ]­indole (Scheme a)…”

Identification, Structure–Activity Relationship, and Biological Characterization of 2,3,4,5-Tetrahydro-1H-pyrido[4,3-b]indoles as a Novel Class of CFTR Potentiators

“…1,2,3,4-Tetrahydro-γ-carbolines represent a chemical class of well-studied heterocycles, extensively characterized for their chemical and biological properties; therefore, as reported by Ivashchenko, such tricyclic compounds could be regarded as typical “privileged structures” . The sustained interest in this scaffold is due to the fact that tetrahydro-γ-carbolines and their derivatives have shown a broad spectrum of biological activities, ,− primarily for the treatment of central nervous system diseases. ,− Although in the last few years substituted derivatives of tetrahydro-γ-carbolines have been reported to be active toward different biological targets, to the best of our knowledge, this type of heterocyclic small molecules has never been described as pharmacologically active compounds for the treatment of CF or related conditions.…”

“…Fischer-indole synthesis starting from phenyl hydrazine 44a in the presence of racemic N-tert-butoxycarbonyl protected 2methyl-piperidin-4-one (49), 2,2-dimethyl piperidin-4-one (56), or 8-azabicyclo[3.2.1]octan-3-one (58) led to the corresponding tetrahydro- (52,53,57) and bridged-(59) 36,37 γ-carbolines. Not surprisingly, whereas mono-methyl intermediates 52 (1-methyl) and 53 (3-methyl) were obtained as a 2:8 regioisomeric mixture, 3,3-gem-dimethyl analogue 57 was afforded as the only regioisomer.…”

Tandem Silver‐Catalyzed Cyclization/Nucleophilic Functionalization of 2‐Alkynylindole‐3‐carbaldehyde Oximes to Afford New 2,4‐Disubstituted γ‐Carbolines

“…Pyrido[4,3‐ b ]indoles, commonly named γ‐carbolines, are an important class of tricyclic heterocycles Many of them have found potent applications in medical domains, with related derivatives demonstrating impressive antipsychotic, anti‐myeloproliferative, and antitumor activities . The great pharmaceutical potential of this scaffold prompted us to search for new and efficient methods that would provide highly diversified structures in a minimum number of steps.…”