A STUDY ON EFFECT OF INDOLE AS A SUBSTITUENT ON A KETO-ENOL TAUTOMER: A SYNTHETIC APPROACH ON β-DIKETONE
DOI:
https://doi.org/10.22159/ijpps.2017v9i8.19576Keywords:
Keto-enol tautomerism, Nil, 6-(1H-Indol-3-yl)-hex-5ene-2, 4-dione, Structural analog, Curcumin, Single crystal XRD, IR, Mass, 1H NMR, DockingAbstract
Objective: The existence of keto-enol tautomerism in β-diketones can typically study by a choice of analytical technique. The position of the keto-enol equilibrium depends on a number of factors like solvent, temperature, and substituents. Here an attempt was made to examine the effect of indole, a heterocyclic moiety with the moderately high polar surface area to examine its effect on ketonisation of β-diketone.
Methods: The β-diketone studied and synthesized is a structural analog of magical drug curcumin. The structural influence of indole on ketonisation of β-diketone is studied to give a hypothesis on factors contributing towards ketonisation. This work involves the synthesis of 6-(1H-Indol-3-yl)-hex-5ene-2, 4-dione and the study on the single crystal structure of indole-3-carboxaldehyde, major functional component to result in the reaction. The tautomer was studied for its ability to bind with tetrahydrofolate reductase enzyme using Discovery Studio 3.5 version to differentiate the pharmacological significance of conformations.
Results: The single crystal XRD structure of this compound was deposited in Cambridge crystallographic data center bearing CCDC No.1536311. The structural characterization of synthesized ligand was carried out by using IR, Mass, 1H NMR spectroscopic techniques. The docking study reveals that keto isomer found to exhibit more inhibition of the enzyme tetrahydrofolate reductase hence more pharmacologically active.
Conclusion: The experimental evidence proves that indole substitution shifted the keto-enol equilibrium towards keto form of 6-(1H-Indol-3-yl)-hex-5ene-2, 4-dione.
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