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H. K. INDURTHI ET AL.
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products derived from marine and terrestrial microorganisms (Fig. 1), e.g., bisindole
sulfate (Arcyria denudate),[2] vibrindole A (Vibrio parahaemolyticus),[3] arsindoline B
(Aeromonas Sp.),[4] rebeccamycin (Lechevalieria aerocolonigenes),[5] and staurosporines
(Streptomyces Sp.).[6] BIMs exhibit a wide range of biological activities such as anti-
cancer,[7] antileishmanial,[8] antioxidant,[9] antibacterial,[10] and antiinflammatory.[11]
Due to its varied pharmacological activities, there is continuous interest in simple, cost-
effective, and green approaches in BIMs synthesis.
In general, synthesis of symmetrical and unsymmetrical BIMs[12] occurs by electro-
philic substitution reaction of indoles with carbonyl compounds in the presence of
Lewis or Bronsted acids,[13] protic acids,[14] solid acid catalysts,[15] organocatalyst,[16]
and metal catalyst.[17] The reusable ionic liquids and heterogeneous catalysts for the
synthesis of BIMs have been developed and overcome some of the limitations caused by
the above developed methods.[18] However, the high cost and acute toxicity of ionic
liquids and the use of organic solvents in heterogeneous catalysts for the synthesis of
BIMs are some of the existing limitations. There are some reports of using water as a
medium,[19] but long-chain alkyl aldehydes give a lower yield of BIMs because of poor
miscibility in water. In recent years, Zhang et al.[20] performed the visible light-induced
aerobic oxidative cross-coupling of glycine derivatives with indoles to synthesize BIMs
in the presence of rhodamine 6 G (Rh-6G) as photocatalyst in dichloromethane, whereas
Qiu and coworkers[21] have demonstrated the UV-light-Induced Friedel ꢀ Crafts alkyl-
ation of indoles with carbonyl compounds in the presence of CF3SO2Na in toluene for
synthesizing BIMs. The use of recyclable Fe/Al pillared clay[22] and hyper-cross-linked
microspheres[23] as catalysts under solvent-free conditions followed green protocol for
the synthesis of BIMs. However, these methods require high temperature hence not use-
ful for low boiling point aldehydes and ketones. Also, the preparation and characteriza-
tion of these catalysts are tedious processes. Based on our previous experience working
with BIM formation from carbonyl compounds in solvent-free reaction conditions, we
have observed that ketones need longer time and high temperatures because of steric
hindrance.[22] Thus, the focus of our current method is the rapid, scalable, and econom-
ical synthesis of BIMs under solvent-free conditions applicable for low to high boiling
point alkyl aldehydes or ketones.
In our previous work, we performed a structure-activity relationship study of BIMs
and observed that BIMs synthesized from 5-bromoindole and alkyl aldehydes are potent
inhibitors of cancer cell proliferation in comparison to the aryl aldehydes.[24] Due to
their importance as potent inhibitors of cancer, and to overcome the limitations of their
synthesis, we have developed a robust and greener protocol for the synthesis of BIMs.
Herein, we demonstrate the microwave-assisted synthesis of BIMs[25] from indoles and
carbonyl compounds by seralite SRC-120. The reason for selecting microwave-assisted
synthesis is a remarkable decrease in reaction time for the products, which required
high temperature and longer time for synthesis.[26] Hence, we speculated that for low
boiling point ketones/aldehydes, microwave-assisted is a useful technique. The seralite
SRC-120 is a commercially available low-cost strongly acidic cation exchange resin that
will act as a catalyst and support for reactants in the microwave. In literature, seralite
SRC-120 used for esterification of ethylene glycol,[27] preparation of resin immobilized
CuO nanoparticles for alcohol oxidation,[28] epoxidation of linseed oil.[29] These
Indurthi, Harish K.
