Efficient microwave-assisted diastereoselective synthesis of indole-based 4,5-dihydrofurans via a one-pot, three-component reaction in water Original Paper First Online: 11 December 2017 Abstract
The combination of two or more different heterocyclic moieties in a single molecule would enhance biological activity significantly. The indole and furan scaffolds are promising candidates in drug design, and they have been widely found in natural products and therapeutic agents. Owing to their pharmaceutical importance, there is an urgent need to design rapid, efficient and environmentally benign protocols for the synthesis of indole–dihydrofuran biheterocycles. Herein, we have developed a novel ecofriendly approach for the diastereoselective synthesis of indole-based 4,5-dihydrofurans through a three-component reaction of 3-cyanoacetyl indoles with various aldehydes and
N-phenacylpyridinium bromides in the presence of potassium carbonate as an inexpensive and non-toxic base in water under low power microwave irradiation. The findings show that aromatic and heteroaromatic aldehydes tolerated well in this reaction. The products were obtained in 85–98% yields in 4–20 min. The advantages of this method consist of the environmental friendly reaction conditions, use of green solvent and safe base, availability of raw materials, wide range of usable substrates, short reaction times, excellent yields and absence of any tedious workup or purification. Keywords Dihydrofuran Microwave Green synthesis Stereoselective Three-component reaction Notes Acknowledgements
We are thankful to the Research Council of Mazandaran University for the financial support of this work.
Azimi R, Baharfar R (2014) DABCO-functionalized mesoporous SBA-15: an efficient and recyclable catalyst for the synthesis of spiro-pyranoxindoles as antioxidant agents. Can J Chem 92:1163–1168.
https://doi.org/10.1139/cjc-2014-0309 CrossRef Google Scholar
Baharfar R, Asghari S, Zaheri F, Shariati N (2017) Three-component synthesis of novel spirooxindole–furan derivatives using pyridinium salts. C R Chim 20:359–364.
https://doi.org/10.1016/j.crci.2016.07.001 CrossRef Google Scholar
Bialonska D, Zjawiony JK (2009) Aplysinopsins-marine indole alkaloids: chemistry, bioactivity and ecological significance. Mar Drugs 7:166–183.
https://doi.org/10.3390/md7020166 CrossRef Google Scholar
Chuang CP, Chen KP (2012)
-Phenacylpyridinium bromides in the one-pot synthesis of 2,3-dihydrofurans. Tetrahedron 68:1401–1406.
https://doi.org/10.1016/j.tet.2011.12.035 CrossRef Google Scholar
Govender T, Maguire GEM, Kruger HG, Shiri M (2013) A review of cyanoacetyl indoles (CAIs): versatile starting materials in organic synthesis. Curr Org Synth 10:737–750.
https://doi.org/10.2174/1570179411310050005 CrossRef Google Scholar
Gunasekaran P, Balamurugan K, Sivakumar S, Perumal S, Menéndez JC, Almansourc AI (2012) Domino reactions in water: diastereoselective synthesis of densely functionalized indolyldihydrofuran derivatives. Green Chem 14:750–757.
https://doi.org/10.1039/c2gc16517a CrossRef Google Scholar
Hailes HC (2007) Reaction solvent selection: the potential of water as a solvent for organic transformations. Org Process Res Dev 11:114–120.
https://doi.org/10.1021/op060157x CrossRef Google Scholar
Kobayashi J, Ohizumi Y, Nakamura H (1986) Hippospongin a novel furanosesterterpene possessing antispasmodic activity from the okinawan marine sponge
sp. Tetrahedron Lett 27:2113–2116.
https://doi.org/10.1016/S0040-4039(00)84462-7 CrossRef Google Scholar
Kupchan SM, Eakin MA, Thomas AM (1971) Tumor inhibitors. 69. Structure-cytotoxicity relations among the sesquiterpene lactones. J Med Chem 14:1147–1152.
https://doi.org/10.1021/jm00294a001 CrossRef Google Scholar
Lakshmi NV, Thirumurugan P, Noorulla KM, Perumal PT (2010) InCl
mediated one-pot multicomponent synthesis, anti-microbial, antioxidant and anticancer evaluation of 3-pyranyl indole derivatives. Bioorg Med Chem Lett 20:5054–5061.
https://doi.org/10.1016/j.bmcl.2010.07.039 CrossRef Google Scholar
Majumder S, Sharma M, Bhuyan PJ (2013) Microwave promoted diastereoselective synthesis of dihydroindeno[1,2-
]furans via one-pot three-component reaction in solvent-free conditions. Tetrahedron Lett 54:6868–6870.
https://doi.org/10.1016/j.tetlet.2013.10.023 CrossRef Google Scholar
Murugavel G, Punniyamurthy T (2015) Microwave-assisted copper-catalyzed four-component tandem synthesis of 3-
-sulfonylamidine coumarins. J Org Chem 80:6291–6299.
https://doi.org/10.1021/acs.joc.5b00738 CrossRef Google Scholar
Rathi AK, Gawande MB, Zboril R, Varma RS (2015) Microwave-assisted synthesis–catalytic applications in aqueous media. Coord Chem Rev 291:68–94.
https://doi.org/10.1016/j.ccr.2015.01.011 CrossRef Google Scholar
Schreiber SL (2000) Target-oriented and diversity-oriented organic synthesis in drug discovery. Science 287:1964–1969.
https://doi.org/10.1126/science.287.5460.1964 CrossRef Google Scholar
Sugimoto K, Tamura K, Tohda C, Toyooka N, Nemoto H, Matsuya Y (2013) Structure–activity-relationship studies on dihydrofuran-fused perhydrophenanthrenes as an anti-Alzheimer’s disease agent. Bioorg Med Chem 21:4459–4471.
https://doi.org/10.1016/j.bmc.2013.05.059 CrossRef Google Scholar
Sun C, Ji SJ, Liu Y (2007) Facile synthesis of 3-(2-furanyl)indoles via a multicomponent reaction. Tetrahedron Lett 48:8987–8989.
https://doi.org/10.1016/j.tetlet.2007.10.098 CrossRef Google Scholar
Sundberg RJ (1996) The chemistry of indoles. Academic Press, New York
Wagare DS, Netankar PD, Shaikh M, Farooqui M, Durrani A (2017) Highly efficient microwave-assisted one-pot synthesis of 4-aryl-2-aminothiazoles in aqueous medium. Environ Chem Lett.
https://doi.org/10.1007/s10311-017-0619-1 CrossRef Google Scholar
Xia L, Idhayadhulla A, Lee YR, Wee YJ, Kim SH (2014) Anti-tyrosinase, antioxidant, and antibacterial activities of novel 5-hydroxy-4-acetyl-2,3-dihydronaphtho[1,2-
]furans. Eur J Med Chem 86:605–612.
https://doi.org/10.1016/j.ejmech.2014.09.025 CrossRef Google Scholar
Zhang Y, Zhong H, Wang T, Geng D, Zhang M, Li K (2012) Synthesis of novel 2, 5-dihydrofuran derivatives and evaluation of their anticancer activity. Eur J Med Chem 48:69–80.
https://doi.org/10.1016/j.ejmech.2011.11.036 CrossRef Google Scholar
Zhang MZ, Chen Q, Yang GF (2015) A review on recent developments of indole-containing antiviral agents. Eur J Med Chem 89:421–441.
https://doi.org/10.1016/j.ejmech.2014.10.065 CrossRef Google Scholar
Zhang D, Zhang Y, Zhao T, Li J, Hou Y, Gu Q (2016) A rapid and efficient solvent-free microwave-assisted synthesis of pyrazolone derivatives containing substituted isoxazole ring. Tetrahedron 72:2979–2987.
https://doi.org/10.1016/j.tet.2016.04.014 CrossRef Google Scholar Copyright information
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