阿糖胞苷衍生物的可控选择性酶促合成与表征

应用简单有效的酶促合成方法可控选择性地合成阿糖胞苷不同官能团的酰化衍生物。通过酶与溶剂之间的选择性调控实现了己二酸二乙烯酯对阿糖胞苷糖环上5′-OH和嘧啶环上4-N的可控选择性酰化,采用FTIR和NMR分析手段对所得到的衍生物的结构进行了确定,并考察了底物摩尔比,反应时间,反应温度对产率的影响。结果表明:脂肪酶Novozym435在无水丙酮中对C′-5位的伯羟基上显示较高的化学选择性,得到单一的5′-O-乙烯己二酰-阿糖胞苷衍生物,产率达到69%,而脂肪酶PS‘Amano’(PS)在无水吡啶中选择性地在N-4位的伯氨基上发生酰化,得到单一的4-N-乙烯己二酰-阿糖胞苷衍生物,产率达到58%。

Controllable Selective Enzymatic Synthesis and Characterization of Cytarabine Derivatives

A facile,efficient controllable selective enzymatic synthesis method for the acylation of different functional groups of cytarabine to prepare acylation derivatives was developed.The controllable acylation of the hydroxyl and amino group of cytarabine with divinyladipate was achieved by changing the enzyme and solvent.The structures of the derivatives were confirmed using FT IR and NMR.The effect of molar ratio of cytarabine to divinyladipate,reaction temperature and reaction time was also investigated.It was found that Novozym 435 in anhydrous acetone showed comparable high chemo-selectivity toward the 5′-OH of cytarabine,and the yield of 5′-O-vinyladipate cytarabine reached 69 %.However,lipase PS ‘Amano’(PS) in pyridine selectively acylated the amino group,and the yield of 4-N-vinyladipate cytarabine reached 58 %.