1-(Propargyl)indol-2-carbonitriles react with alcohols to afford 1-alkoxypyrazino[1,2- a]indoles under DBU-catalyzed microwave-assisted conditions. The reaction scope includes a wide range of indoles, primary and secondary alcohols, and a thiol. The initial mechanistic study shows that the domino process presumably proceeds through an alkyne-allene rearrangement, imidate formation, and nucleophilic cyclization reaction sequence.
N-(Propargyl)indole-2-carbonitriles undergo DBU-catalyzed addition of CH-acids to nitriles, followed by cyclization to give 9-aminopyrido[1,2-a]indoles.
This work was focused on understanding the interaction mechanism of pyrazino[1,2‐a]indole derivative in calf thymus DNA (ctDNA) using various spectroscopy and computational techniques. The UV‐Vis absorption result shows that the binding interaction of pyrazino[1,2‐a]indole derivative in ctDNA complex may be in the non –covalent form and the binding associate constant Ka value was estimated 7.06×103 L mol−1 at 297 K. The fluorescence emission spectroscopy analysis suggested that pyrazino[1,2‐a]indole derivative quenching mechanism in ctDNA mainly due to the static nature and thermodynamical parameter analysis implied the binding of pyrazino[1,2‐a]indole derivative in ctDNA mainly due to hydrophobic force. Forster resonance energy transfer analysis was also calculated and the r=2.1 nm. Circular dichroism spectra conclude that there is a change in the secondary structural region of ctDNA due to an interaction with pyrazino[1,2‐a]indole derivative. Together with the molecular docking studies, hydrophobic nature of the interaction of pyrazino[1,2‐a]indole derivative with ctDNA might be deduced.
Interactions of N-(propargyl)indole-2-carbonitrileswith nitrogen nucleophiles were studied. It was found that lithium hexamethyldisilazane (LiHMDS)-promoted reactions give mixtures of two product types, originating from an initial attack onto carbon−carbon or carbon−nitrogen triple bonds. Performing the reaction at reduced temperature and in the presence of catalytic amounts of LiHMDS delivered alkyne hydroamination products exclusively. On the contrary, the one-pot reaction of N-(propargyl)indole-2-carbonitriles with methanol and LiHMDS on heating, followed by the addition of a nitrogen nucleophile, allowed a selective domino cyclization sequence toward 1-aminopyrazino-[1,2-a]indoles. Anilines and nitrogen heterocycles could be employed as N-nucleophiles to obtain products of both types. Moreover, an alternative one-pot route toward a third product type has been developed. When N-(propargyl)indole-2-carbonitrile was first combined with aniline and LiHMDS at reduced temperature, further heating of the in situ generated hydroamination product led to the intramolecular cyclization into 1-imino-2-phenylpyrazino[1,2-a]indoles. Thus, chemodivergent transformations of the same starting material into three compound classes were investigated. The possible reaction routes were studied, and N-(allenyl)indole-2carbonitrile was identified as the key intermediate. Acyclic and cyclic products exhibit fluorescence emission in the blue to green range.
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