Yakup BUDAK, Ahmet Doğan ÇAKIR, Oğuz ÖZBEK, Meliha Burcu GÜRDERE, Mustafa CEYLAN

İsoindolsübstitüe-kalkon Türevlerine İyot Katalizli Tiyofenol Katılması

Kalkon ve isoindol türevleri önemli biyolojik aktivitelere sahip bileşiklerdir. Bu iki birimi aynı yapıda taşıyan hibrit moleküllerinde biyolojik aktivite gösterdikleri bilinmektedir. Ayrıca β-merkaptanlar bazı biyoaktif bileşiklerin sentezi için başlangıç materyali olarak kullanılmaktadırlar. Bu çalışmada, isoindolsübstitüe-kalkon türevlerine (3a-j) moleküler iyot katalizörlüğünde tiyofenol katılarak yeni β-merkapto karbonil bileşikleri, ((3aR,4S,7R,7aS)-2-(4-(3-(feniltiyo)-3-(aril)propanol)fenil)-3a,4,7,7a-tetrahidro-1H-4,7-metanisoindol-1,3(2H)-dion) (5a-j) yüksek verimler ile elde edildi. Elde edilen yeni bileşiklerin yapıları 1H-NMR, 13C-NMR, FT-IR ve Elementel Analiz spektroskopik yöntemleri kullanılarak aydınlatıldı.

Iodine-Catalyzed Addition of Thiophenol to Isoindolsubstitue Chalcones

Chalcone and isoindol derivatives possess significant biological activities. Also, ıt is known that hybrid molecules carrying these two units in the same structure show biological activity. In addition, -mercaptans are used as the starting material for the synthesis of some bioactive compounds. In this work, new β-mercapto carbonyl compounds (5a-j), (3aR,4S,7R,7aS)-2-(4-(3-(phenylthio)-3-(aryl)pyridyl)aminocarbonyl-propanol)phenyl)-3a,4,7,7a-tetrahydro-1H-7-methanoisoindole-1,3(2H)-dione), were obtained by molecular iodine-catalyzed addition of thiophenol to isoindol substituted chalcone derivatives (3a-j) in high yields. The structures of the obtained new compounds were clarified by 1H-NMR, 13C-NMR, FT-IR and Elemental Analysis spectroscopic methods.

Keywords:

Chalcone, Isoindole, Thiophenol, β-Mercaptocarbonyl,

PDF

___

[1] Rida, S. M., Labouta, I. M., Salama, H. M., Ghany, Y. S., El-Ghazzaui, E., Kader, O. (1986). Syntheses and in vitro antimicrobial evaluation of some benzimidazol-2-ylmethyl-thioureas, enzimidazol 2-ylacetyl thiosemicarbazides and products of their condensation with monochloroacetic acid. Pharmazie, 41, 475- 478.
[2] Bhat, A. R., Singh, D. (1988). Synthesis and biological activities of 4-thiazolidinones and dihydro-3-(2H)- thiophenones. Indian Journal of Pharmaceutical Sciences, 50, 169-171.
[3] Pandeya, D., Nair, K. B. (1993). Bridged bis(4-thiazolidinones) and related compounds with antibacterial activity. Pharmazie, 48, 414-417.
[4] Franchini, C., Muraglia, M., Corbo, F., Florio, M. A., Di Mola, A., Rosato, A., Matucci, R., Nesi, M., VanBambeke, F., Vitali, C. (2009). Synthesis and biological evaluation of 2-mercapto-1,3-benzothiazole derivatives with potential antimicrobial activity. Archiv der Pharmazie, 342, 605-613.
[5] Cesur, N., Cesur, Z., Ergenc, N., Uzun, M., Kiraz, M., Kasimoglu, O., Kaya, D. (1994). Synthesis and antifungal activity of some 2-aryl-3-substituted 4-thiazolidinones. Archiv der Pharmazie, 327, 271-272.
[6] Capan, G., Ulusoy, N., Ergenc, N., Kiraz, M. (1999). New 6-phenylimidazo[2,1-b]thiazole derivatives: synthesis and antifungal activity. Monatshefte für Chemie, 130, 1399-1407.
[7] Bhatt, J. J., Shah, B. R., Shah, H. P., Trivedi, P. B., Undavia, N. K., Desai, N. C. (1994). Synthesis of antiHIV, anticancer and antitubercular 4-oxo-thiazolidines, 2-imino-4-oxo-thiazolidines and their 5-arylidine derivatives. Indian Journal of Chemistry, 33B, 189-192.
[8] Tandon, K.V., Chhor, R. B., Singh, R. V., Rai, S., Yadav, D. B. (2004). Design, synthesis and evaluation of novel 1,4-naphthoquinone derivatives as antifungal and anticancer agents. Bioorganic & Medicinal Chemistry Letters, 14, 1079-1083.
[9] Sheela, C. G., Augusti K. T. (1992). Antidiabetic effects of S-allyl cysteine sulphoxide isolated from garlic Allium sativum Linn. Indian Journal of Experimental Biology, 30, 523-526.
[10] Mahmoodi, M., Aliabadi, A., Emami, S., Safavi, M., Rajabalian, S., Mohagheghi, M. A., Khoshzaban, A., Kermani, A. S., Lamei, N., Shafiee, A., Foroumadi, A. (2010). Synthesis and in-vitro Cytotoxicity of Polyfunctionalized 4-(2-Arylthiazol-4-yl)-4H-chromenes. Archiv der Pharmazie, 343, 411-416.
[11] Katristzky, A. R., Button, M. A. (2001). Efficient syntheses of thiochromans via cationic cycloadditions. Journal of Organic Chemistry, 66, 5595-5600.
[12] Ram, V. J., Agarwal, N., Saxena, A. S., Farhanullah, S., Sharon, A., Maulik, P. R. (2002). Carbanion induced synthesis of annulated unsymmetrical biaryls through ring transformation of 2H-pyran-2-one. Journal of the Chemical Society, Perkin Transactions 1, 1, 1426-1437.
[13] Van-Vliet, L. A., Rodenhuis, N., Dijkstra, D., Wikström, H., Pugsley, T. A., Serpa, K. A., Meltzer, L. T., Heffner, T. G., Wise, L. D., Lajiness, M. E., Huff, R. M., Svensson, K., Sundell, S., Lundmark, M. (2000). Synthesis and pharmacological evaluation of thiopyran analogues of the dopamine D3 receptor-selective agonist (4aR,10bR)-(+)-trans-3,4,4a,10b-Tetrahydro-4-n-propyl-2H,5H-[1]benzopyrano [4,3-b]-1,4-oxazin9-ol (PD 128907). Journal of Medicinal Chemistry, 43, 2871-2882.
[14] Khatik, G. L., Kumar, R., Chakraborti, A. K. (2007). Magnesium Perchlorate as a New and Highly Efficient Catalyst for the Synthesis of 2,3-Dihydro-1,5-benzothiazepines. Synthesis, 4, 541-546.
[15] Sharma, G., Kumar, R., Chakraborti, A. K. (2008). On water’ synthesis of 2,4-diaryl-2,3-dihydro-1,5- benzothiazepines catalysed by sodium dodecyl sulfate (SDS). Tetrahedron Letter, 49, 4269-4271.
[16] Zielinska-Blajet, M., Kowalczyk, R., Skarzewski, J. (2005). Ring-closure reactions through intramolecularsubstitution of thiophenoxide by oxygen and nitrogen nucleophiles: simple stereospecific synthesis of 4,5-dihydroisoxazoles and 4,5-dihydropyrazoles. Tetrahedron, 61, 5235-5240.
[17] Garg, S. K., Kumar, R., Chakraborti, A. K. (2005). Copper(II) tetrafluoroborate as a novel and highly efficient catalyst for Michael addition of mercaptans to a,b-unsaturated carbonyl compounds. Tetrahedron Letter, 46, 1721-1724.
[18] Cheng, S., Cromer, D. D. (2002). An alumina-catalyzed Michael addition of mercaptans to N-anilinomaleimides and its application to the solution-phase parallel synthesis of libraries. Tetrahedron Letters, 43, 1179-1181.
[19] Lee, P. H., Ahn, H., Lee, K., Sung, S. Y., Kim, S. (2001). Studies on the reactions of -enones with allyl indium reagent; effects of TMSCI as promoter on regioselectivity. Tetrahedron Letters, 42, 37-39.
[20] Jovanovic, B. Z., Misic, V. M., Marinkovic, A. D., Csanadi, J. (1999). 13C NMR spectra of pyridine chalcone analogs. Journal of Molecular Structure, 482-483, 371-374.
[21] Ram V.J., Saxena A.S., Srivastava S., Chandra S. (2000). Oxygenated chalcones and bischalcones as potential antimalarial agents. Bioorganic & Medicinal Chemistry Letters, 10, 2159-2161.
[22] Rolf, V.H., Wellinga, K. ve Grosscurt, C. (1978). 1-Phenylcarbamoyl-2-pyrazolines: a new class of insecticides. 2. Synthesis and insecticidal properties of 3,5-diphenyl-1-phenylcarbamoyl-2-pyrazolines. Journal of Agricultural and Food Chemistry, 26, 915-918.
[23] Ankhiwala, M.D. (1990). Studies on flavonoids, part II: Synthesis and antimicrobial activity of 8-bromo-7- n-butoxy-6-nitroflavones, -flavonols, and flavanones. Journal of Indian Chemical Society, 67, 913-915.
[24] Wu J.-H., Wang X.-H., Yi Y.-H. ve Lee K.-H. (2003). Anti-AIDS agents 54. A potent anti-HIV chalcone and flavonoids from genus Desmos. Bioorganic & Medicinal Chemistry Letters, 13, 1813-1815.
[25] Kumar S.K., Erin H., Catherina P., Gurulingappa, H., Davidson, N. E. ve Khan, S. R. (2003). Design, synthesis, and evaluation of novel boronic-chalcone derivatives as antitumor agents. Journal of Medicinal Chemistry, 46, 2813-2815.
[26] Buolamwını, J. K., Addo, J., Kamath, S., Patıl, S., Mason, D., Ores, M. (2005). Small molecule antagonists of the MDM2 oncoprotein as anticancer agents. Current Cancer Drug Targets, 5, 57-68.
[27] Herencia, F., Ferrandiz, M. L., Ubeda, A., Dominguez, J. N., Charris, J. E., Lobo, G. M. ve Alcarez, M. J. (1998). Synthesis and anti-imflammatory activity of chalcone derivatives, Bioorganic & Medicinal Chemistry, 8, 1169-1174.
[28] Satyanarayana, M., Tiwari, P., Tripathi, B. K., Srivastava, A. K., Pratap, R. (2004). Synthesis and antihyperglycemic activity of chalcone based aryloxypropanolamines. Bioorganic & Medicinal Chemistry, 12, 883-889.
[29] Fayed, T. A., Awad, M. K. (2004). Dual emission of chalcone-analogue dyes emitting in the red region. Chemical Physics, 303, 317-326.
[30] Gürdere, M. B., Özbek, O., Ceylan, M. (2016). Aluminum chloride–catalyzed C-alkylation of pyrrole and indole with chalcone and bis-chalcone derivatives. Synthetic Communications, 46, 322-331.
[31] Ozbek, O., Usta, N. C., Gürdere, M B., Aslan, O. A., Budak, Y., Ceylan, M. (2017). Synthesis and antibacterial screening of novel 2-(4-(aryl) thiazol-2-yl)-3a,4,7,7a-tetrahydro-1H-4,7-ethanoisoindole1,3(2H)-dione derivatives. Phosphorus, Sulfur, and Silicon and the Related Elements, 192, 1153-1157.
[32] Gilchrist, T. L. (1987). Heterocyclic Chemistry, 2. baskı, Harlow, Essex, England : Longman Scientific & Technical, Wiley, New York.
[33] Sun, L., Tran, N., Liang C., Hubbard, S., Tang F., Lipson K., Schreck, R., Zhou Y., McMahon, G., Tang, C. (2000). Identification of substituted 3-[(4,5,6, 7-tetrahydro-1H-indol-2-yl)methylene]-1,3-dihydroindol2-ones as growth factor receptor inhibitors for VEGF-R2 (Flk-1/KDR), FGF-R1, and PDGF-Rbeta tyrosine kinases. Journal of Medicinal Chemistry, 43(14), 2655-2663.
[34] Kocyigit, U. M., Budak, Y., Gürdere, M. B., Tekin, Ş., Kul Köprülü, T., Ertürk, F., Özcan, K., Gülçin, I., Ceylan, M. (2017). Synthesis, characterization, anticancer, antimicrobial and carbonicanhydrase inhibition profiles of novel (3aR,4S,7R,7aS)-2-(4-((E)-3-(3-aryl) acryloyl) phenyl)-3a,4,7,7a-tetrahydro-1H-4,7- methanoisoindole-1,3(2H)-dione derivatives. Bioorganic Chemistry, 70, 118–125.
[35] Budak, Y., Kocyigit, U. M., Gürdere, M. B., Özcan, K., Taslimi, P., Gülçin, İ., Ceylan, M. (2017). Synthesis and investigation of antibacterial activities and carbonic anhydrase and acetyl cholinesterase inhibition profiles of novel 4,5-dihydropyrazol and pyrazolyl-thiazole derivatives containing methanoisoindol-1,3-dion unit. Synthetic Communications, 47 (24), 2313–2323.
[36] Ceylan, M., Gürdere, M. B., Karaman, İ., Gezegen, H. (2011). The synthesis and screening of the antimicrobial activity of some novel 3-(furan-2-yl)-1-(aryl)-3-(phenylthio)propan-1-one derivatives. Medicinal Chemistry Research, 20, 109-115.