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A New Process for Deprotection of Acetyl and Benzoyl Groups in Synthesis of Azacitidine
Corresponding Author(s) : Srujana Suneel Kumar
Asian Journal of Chemistry,
Vol. 30 No. 7 (2018): Vol 30 Issue 7
Abstract
4-Amino-1-β-D-ribofuranosyl-s-triazin-2(1H)-one or azacitidine is a promising DNA demethylation inhibitor used for the treatment of myloneplastic, bone cancer and breast cancer. An efficient, cost-effective and convenient manufacturing process for the synthesis of azacitidine is described. The present research relates to the synthesis, deprotection, isolation and purification of azacitidine (1). In this process, more particularly 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is used as deprotection reagent for deprotection of O-acetyl, O-benzoyl to acquire azacitidine (1). The new process allows for the reliable and efficient production of drug substance similar overall yield. The new improved process has merits including enantiomeric purity, better crystallization and the product complies with the requirements of USP30.
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References
A. Cihák, Oncology, 30, 405 (1974); https://doi.org/10.1159/000224981.
P.T. Diamantopoulos, M. Michael, O. Benopoulou, E. Bazanis, G. Tzeletas, J. Meletis, G. Vayopoulos and N.-A. Viniou Virol. J., 9, 1 (2012); https://doi.org/10.1186/1743-422X-9-1.
R.C. Hartenstein and I. Fridovich, J. Org. Chem., 32, 1653 (1967); https://doi.org/10.1021/jo01280a095.
A. Piskala, Collect. Czech. Chem. Commun., 32, 3966 (1967); https://doi.org/10.1135/cccc19673966.
A.G. Dinmohamed, Y. van Norden, O. Visser, E F M. Posthuma, P.C. Huijgens, P. Sonneveld, A.A. van de Loosdrecht and M. Jongen-Lavrencic, Leukemia, 29, 2449 (2015); https://doi.org/10.1038/leu.2015.220.
R. Garcaa-Delgado, D. de Miguel, A. Bailén, J.R. Gonzalez, J. Bargay, J.F. Falantes, R. Andreu, F. Ramos, M. Tormo, S. Brunet, A. Figueredo, J. Casaño, Á. Medina, L. Badiella, A.F. Jurado and G. Sanz, Leukemia Res., 38, 744 (2014); https://doi.org/10.1016/j.leukres.2014.03.004.
N.R. Palepu, P.C. Buxton and B.B. Teja, Stable Formulations of Azacitidine, WO 2011014541 A1 (2011).
M.W. Winkley and R.K. Robins, J. Org. Chem., 35, 491 (1970); https://doi.org/10.1021/jo00827a045.
U. Niedballa and H. Vorbrueggen, J. Org. Chem., 39, 3672 (1974); https://doi.org/10.1021/jo00939a012.
H. Vorbrüggen and C. Ruh-Pohlenz, Org. React., 55, 100 (2000); https://doi.org/10.1002/0471264180.or055.01.
D. Ionescu and P. Blumbergs, Synthesis of 5-Azacytidine, US Patent 8058424B2 (2011).
F. Ishikawa, A. Nomura, T. Ueda, M. Ikehara and Y. Mizuno, Chem. Pharm. Bull., 8, 380 (1960); https://doi.org/10.1248/cpb.8.380.
S.S.K. Madana, V. Sethuraman and N. Gupta, Asian J. Chem., 28, 429 (2016); https://doi.org/10.14233/ajchem.2016.19409