α-D-5-azacytidine is a potential impurity during the preparation of the nucleoside drugβ-D-5-azacytidine. It is extremely important to obtain high-purityα-D-5-azacytidine as a standard sample for quality control ofβ-D-5-azacytidine. Herein the first synthetic route ofα-D-5-azacytidine by a five-step strategy with an overall yield of 48%from natural D-ribose has been established. The crucialα-ribonucleosidic bond is directly constructed via the Lewis acid-catalysed Silyl-Hilbert-Johnson reaction under the condition of SnCl4/CH2Cl2/-25℃.Thissyntheticstrategyissimple,inexpensive,high-yieldandclearlysuitableforlarge-scalepreparations.% 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。
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