Synthesis of Novel Ure Derivatives of Artemisinin
Main Article Content
Abstract
The synthesis of novel artemisinin derivatives containing ure linkages 6a-c was described. 10ẞ- azidoartemisinin (4) was first obtained in good yield by the reaction of dihydroartemisinin (2) with NaN3 in the presence of (CH3)3SiCI and a catalytic amount of KI in CH2Cl2 at ice water temperature. This compound was then hydrolyzed by Ph3P in THF/H2O at 65°C for 6 h to furnish 10ẞ-aminoartemisinin (5). The reaction of 5 with different isocyanates in CH2Cl2 at ambient temperature gave the target compounds 6a-c. The structures of synthesized compounds were confirmed based on spectroscopic methods: H and ¹³C NMR and comparison with published data.
Keywords
Artemisinin, dihydroartemisinin, artemether, arteether, sodium azide, isocyanate
Article Details
References
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[13]. Le Huy Binh, Nguyen Thanh Binh, Nguyen Thi Thuy Van, Tran Khac Vu. Nghiên cứu tổng hợp chọn lọc 108-azidoartemisinin. Vietnam J. Chem. 53 (2015). 35-40.
[2]. Lin, A. J.; Lee, M.; Klayman. D. L. Antimalarial activity of new water-soluble dihydroartemisinin derivatives. 2. Stereospecificity of the ether side chain. J. Med. Chem., 32 (1989) 1249-1252.
[3]. Lin, A. J.: Klayman. D. L.; Milhous, W. K. Antimalarial activity of new water-soluble dihydroartemisinin derivatives. J. Med. Chem., 30, (1987) 2147-2154.
[4]. Lin, A. J.; Miller, R. E. Antimalarial activity of new dihydroartemisinin derivatives. 6. alpha- Alkylbenzylic ethers. J. Med. Chem., 38 (1985) 764- 770.
[5]. Brewer. T. G.; Peggins, J. O.; Grate, S. J.; Petras, J. M.: Levin. B. S.; Weina, P. J.; Swearengen, J.; Heiffer, M, H. Neurotoxicity in animals due to arteether and artemether. Trans. R. Soc. Trop. Med. Hyg., 88(1994) 33-36.
[6]. Lee, S. Artemisinin, promising lead natural product for various drug developments. Mini Rev. Med. Chem., 7 (2007) 411-422.
[7]. Goswami A, Saikia PP, Saikia B, Barua NC, Saxena AK, Suri N, Sharma M, Baishya G.Synthesis of a novel series of highly functionalized Baylis Hillman adducts of artemisinin with potent anticancer activity. Tetrahedron Lett. 32 (2013)4221-4224.
[8]. Jung M, Park N, Moon H-I, Lee Y, Chung W-Y, Park K-K (2009) Synthesis and anticancer activity of novel amide derivatives of non-acetal deoxoartemisinin. Bioorg Med Chem Lett. 22 (2009)6303-6306.
[9]. Lee S. Synthesis of 10ß-substituted triazolyl artemisinins and their growth inhibitory activity against various cancer cells. Bull Korean Chem Soc 32 (2011)737-740.
[10]. Le Huy Binh, Nguyen Thi Thuy Van, Vu Tuan Kien, Nguyen Thi Thuy My, Luu Van Chinh, Nguyen Thi Nga, Hoang Xuan Tien, Tran Khac Vu. Synthesis and In VitroEvaluation of New Triazole Derivatives Based on Artemisinin via Click Chemistry. Medicinal Chemistry Research. 25 (2016) 738-750.
[11]. Vu Thi Ha, Vu Tuan Kien, Le Huy Binh, Vu Dinh Tien, Nguyen Thi Thuy My. Nguyen Hai Nam, Michael Baltas, Hyunggu Hahn, Byung Woo Han, Do Thi Thao, Tran Khac Vu. Design, synthesis and biological evaluation of novel hydroxamic acids bearing artemisinin skeleton. Bioorganic Chemistry. 66 (2016), 63-71.
[12]. Lijun X., Xin Z., Lixiang R., Haiyan M., Chun L., Wufu Z., Yanfang Z. Design, Synthesis and Antitumor Activity of Novel Artemisinin Derivatives Using Hybrid Approach. Chem. Pharm. Bull., 59 (2011) 984-990.
[13]. Le Huy Binh, Nguyen Thanh Binh, Nguyen Thi Thuy Van, Tran Khac Vu. Nghiên cứu tổng hợp chọn lọc 108-azidoartemisinin. Vietnam J. Chem. 53 (2015). 35-40.