Novel L-amino acid ester prodrugs of azacitidine: Design, enzymatic synthesis and the investigation of release behavior

作者：Xu, Fan; Zhang, Ming; Wu, Qi^*; Lin, Xianfu

来源：Journal of Molecular Catalysis B: Enzymatic , 2014, 105: 49-57.

DOI：10.1016/j.molcatb.2014.03.018

• Regioselectivity
• Amino acid-azacitidine conjugates
• Azacitidine
• Amino acid ester prodrug
• Enzymatic synthesis

A facile, enzymatic synthesis protocol of L-amino acid ester prodrugs of azacitidine was developed. Firstly, transesterification of azacitidine with Boc protected vinyl aminocarboxylates was performed under the catalysis of subtilisin in anhydrous pyridine at 50 degrees C. A series of Boc-protected amino acid-azacitidine conjugates were prepared in good regioselectivity and yield. Various factors which influence the catalytic efficiency were systematically investigated. And then, the obtained azacitidine derivatives were subjected to a deprotection process to give L-amino acid ester prodrugs of azacitidine. In vitro hydrolysis of prodrugs showed that the amino acid ester prodrugs had obvious sustained release characteristic. These characteristics will have potential value for clinic application.

• 出版日期2014-7
• 单位浙江大学