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α-D-5-氮杂胞苷是生产核苷药物β-D-5-氮杂胞苷时极易产生的一种杂质。高纯度的α-D-5-氮杂胞苷可以作为标准品,用以控制β-D-5-氮杂胞苷的药物质量。通过实验研究建立了以天然D-核糖为原料,经5步反应,制备高纯度α-D-5-氮杂胞苷的合成路线,总收率48%。其中关键的α-核苷键是通过路易斯酸催化的Silyl-Hilbert-Johnson反应,在SnCl4/CH2Cl2/-25℃的条件下直接构建的。这一路线具有简洁、低成本和高收率的特点,非常适合大规模制备α-D-5-氮杂胞苷。
α-D-5-azacytidine is an impurity that is easily produced when β-D-5-azacytidine is used as a nucleoside drug. High-purity α-D-5-azacytidine can be used as a standard to control the drug quality of β-D-5-azacytidine. Through the experimental research, a synthetic route of natural D-ribose as raw material and 5 steps of high purity α-D-5-azacytidine was established. The total yield was 48%. Among them, the key α-nucleoside bond was directly constructed by Lewis acid-catalyzed Silyl-Hilbert-Johnson reaction under the condition of SnCl4 / CH2Cl2 / -25 ℃. This route is characterized by its simplicity, low cost and high yield, making it well suited for the large-scale production of α-D-5-azacytidine.