Chinese Journal of Organic Chemistry >
A New Method for the Synthesis of Clofarabine
Received date: 2014-01-14
Revised date: 2014-02-22
Online published: 2014-03-03
Supported by
Foundation of Henan Scientific Committee (No. 114100510012), the Program for Innovative Research Team from the University of Henan Province (No. 2012IRTSTHN006), the Research Fund for the Doctoral Program of Higher Education (No. 20124104110006).
Clofarabine is the active ingredient in the anti-pediatric leukemia drug, which was approved by U.S. Food and Drug Administration in 2004. However, the previous reported methods have long steps, low yield and difficult separation of α/β anomers, which restrict the wide use of the drug. In this manuscript, the cheap and commercial available 2-chloroadenosine was chose as the starting material to synthesize the clofarabine. By using acetic acid and hydrazine, the selective deprotection of acetyl group in 2'-position was accomplished. Subsequently, the fluorination step was realized by diethylaminosulfurtrifluoride (DAST). The clofarabine was synthesized with 4 steps in 49% total yield as a pure β-anomer. Meanwhile, the strong steric hindrance of 2-substitution was favorable for the 2'-deacetylation. Notably, the clofarobine could be synthesized at a gram scale using this method, which showed the good future of industrial application.
Key words： clofarabine; 2-chloroadenosine; fluorination; synthesis; nucleoside
Xia Ran , Guo Zhen , Qin Bowen , Ji Zhiyue , Xie Mingsheng , Qu Guirong , Guo Haiming . A New Method for the Synthesis of Clofarabine[J]. Chinese Journal of Organic Chemistry, 2014 , 34(6) : 1154 -1160 . DOI: 10.6023/cjoc201401024
[1] (a) Lee, S.; Uttamapinant, C.; Verdine, G. L. Org. Lett. 2007, 9, 5007.
(b) Chong, Y.; Choo, H.; Choi, Y.; Mathew, J.; Schinazi, R. F.; Chu, C. K. J. Med. Chem. 2002, 45, 4888.
[2] Xu, X.-H.; Qiu, X.-L.; Zhang, X.-G.; Qing, F.-L. J. Org. Chem. 2006, 71, 2820.
[3] Yamauchi, T.; Nowak, B. J.; Keating, M. J.; Plunkett, W. Clin. Cancer Res. 2001, 7, 3580.
[4] Kantargian, H. M.; Gandhi, V. V.; O'Brien, S.; Giles, F.; Coertes, J.; Kozuch, P.; Du, M.; Plunkett, W.; Rios, M. B.; Freireich, E. J.; Estey, E. H.; Keating, M. J. Blood 2001, 98, 214b Abstract 4568.
[5] Montgomery, J. A.; Shortnacy-Fowler, A. T.; Clayton, S. D.; Riordan, J. M.; Secrist III, J. A. J. Med. Chem. 1992, 35, 397.
[6] Montgomery, J. A.; Fowler, A. T.; Secrist III, J. A. WO 2001060383, 2001 [Chem. Abstr. 2001, 135, 180927].
[7] Bauta, W. E.; Schulmeier, B. E.; Burke, B.; Puente, J. F.; Cantrell, Jr.; Lovett, W. R. D.; Goebel, J.; Anderson, B.; Ionescu, D.; Guo, R.-C. Org. Process Res. Dev. 2004, 8, 889.
[8] Anderson, B. G.; Bauta, W. E.; Cantrell, Jr. W. R.; Engles, T.; Lovett, D. P. Org. Process Res. Dev. 2008, 12, 1229.
[9] (a) Wright, J. A.; Taylor, N. F.; Fox, J. J. J. Org. Chem. 1969, 34, 2632.
(b) Watanable, K. A.; Chu, C. K.; Fox, J. J.; Reichman, U.; Watanabe, K. A.; Fox, J. J. Carbohyd. Res. 1975, 42, 233.
[10] Henschke, J. P.; Zhang, X.-H.; Mei, L.-J.; Chen, Y.-F. US 20120010397, 2012 [Chem. Abstr. 2012, 156, 99519].
[11] (a) Guo, H.-M.; Wu, Y.-Y.; Niu, H.-Y.; Wang, D.-C.; Qu, G.-R. J. Org. Chem. 2010, 75, 3863.
(b) Guo, H.-M.; Xia, C.; Niu, H.-Y.; Zhang, X.-T.; Kong, S.-N.; Wang, D.-C.; Qu, G.-R. Adv. Synth. Catal. 2011, 353, 53.
(c) Guo, H.-M.; Yuan, T.-F.; Niu, H.-Y.; Liu, J.-Y.; Mao, R.-Z.; Li, D.-Y.; Qu, G.-R. Chem. Eur. J. 2011, 17, 4095.
(d) Niu, H.-Y.; Yuan, T.-F.; Qu, G.-R.; Li, D.-Y.; Mao, R.-Z.; Jin, X.; Yang, X.-N.; Guo, H.-M. Chin. J. Org. Chem. 2011, 31, 1613.
(e) Niu, H.-Y.; Zhang, X.-T.; Zhao, G.-Y.; Li, N.; Kong, S.-N.; Xia, C.; Qu, G.-R.; Guo, H.-M. Chin. J. Org. Chem. 2011, 31, 695.
(f) Wang, D.-C.; Niu, H.-Y.; Guo, H.-M.; Wei, X.-J.; Ding, R.-F.; Qu, G.-R. Chin. J. Org. Chem. 2012, 32, 1072.
(g) Meng, G.; Niu, H.-Y.; Qu, G.-R.; Fossey, J. S.; Li, J.-P.; Guo, H.-M. Chem. Commun. 2012, 48, 9601.
(h) Qu, G.-R.; Liang, L.; Niu, H.-Y.; Rao, W.-H.; Guo, H.-M.; Fossey, J. S. Org. Lett. 2012, 14, 4494.
(i) Xin, P.-Y.; Niu, H.-Y.; Qu, G.-R.; Ding, R.-F.; Guo, H.-M. Chem. Commun. 2012, 48, 6717.
(j) Li, J.-P.; Huang, Y.; Xie, M.-S.; Qu, G.-R.; Niu, H.-Y.; Wang, H.-X.; Qin, B.-W.; Guo, H.-M. J. Org. Chem. 2013, 78, 12629.
(k) Wang, D.-C.; Niu, H.-Y.; Xie, M.-S. Qu, G.-R.; Wang, H.-X.; Guo, H.-M. Org. Lett. 2014, 16, 262.
(l) Xia, R.; Xie, M.-S.; Niu, H.-Y.; Qu, G.-R.; Guo, H.-M. Org. Lett. 2014, 16, 444.
(m) Wei, T.; Xie, M.-S.; Qu, G.-R.; Niu, H.-Y.; Guo, H.-M. Org. Lett. 2014, 16, 900.
(n) Xie, M.-S.; Chu, Z.-L.; Qu, G..-R.; Niu, H.-Y.; Guo, H.-M. J. Org. Chem. 2014, 79, 1093.
[12] Guo, H.-M.; Wu, S.; Niu, H.-Y.; Song, G.; Qu, G.-R. In Chemical Synthesis of Nucleoside Analogues 3, Ed.: Merino, P., John Wiley & Sons, New York, 2013, pp. 103～162.
[13] Robins, M. J.; Wilson, J.; Sawyer, L.; James, M. G. Can. J. Chem. 1983, 61, 1911.
[14] Wagner, D.; Verheyden, J. H.; Moffatt, J. G. J. Org. Chem. 1974, 39, 24.
[15] Ishido, Y.; Sakairi, N.; Okazaki, K.; Nakazaki, N. J. Chem. Soc., Perkin Trans. 1 1980, 563.
[16] Nowak, I.; Jones, C. T.; Robins, M. J. J. Org. Chem. 2006, 71, 3077.
[17] Robins, M. J.; Uznański, B. Can. J. Chem. 1981, 59, 2601.
[18] Ishido, Y.; Nakazaki, N.; Sakairi, N. J. Chem. Soc., Perkin Trans. 1 1979, 2088.
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