无金属催化合成2,6-二氯嘌呤核苷和2-氯腺苷

Metal-free Synthesis of 2,6-Dichloropurineside and 2-Chloroadenosine

提出了合成2,6-二氯嘌呤核苷和2-氯腺苷的新方法。以商品化的2,6-二氯嘌呤和四乙酰核糖为原料,在5%(摩尔分数)三氟甲磺酸催化下,得到缩合物2',3',5'-三-O-乙酰基-2,6-二氯嘌呤核苷。缩合物在浓H_2SO_4催化下,以89%的收率得到2,6-二氯嘌呤核苷;在NH_3/CH_3OH体系中氨解和脱除乙酰基,以92%的收率得到2-氯腺苷。反应规模可以扩大到100 g,收率未降低。该方法原料价格低廉,避免使用重金属催化剂,操作简便,中间体及产物可以通过结晶的方法纯化得到,显示出潜在的应用价值。

New methods for the synthesis of 2,6-dichloropurineside and 2-chloroadenosine were developed. The key intermediate 2＇,3＇,5＇-tri-O-acetyl-2,6-dichloropurineside was obtained from the condensation of 2,6-dichloropurine and β-D-ribofuranose 1,2,3,5-tetraacetate under the catalysis of 5% molar fraction of trifluoromethanesulfonic acid. 2,6-Dichloropurineside was obtained by sulfuric acid catalyzed hydrolysis of 2＇,3＇,5＇-tri-O-acetyl-2,6-dichloropurineside in the yield of 89% and 2-chloroadenosine was obtained from the aminolysis of 2＇,3＇,5＇-tri-O-acetyl-2,6-dichloropurineside in NH3/CH3OH with the yield of 92%. The starting substrates were all commercially available and affordable. The presented method avoided toxic metal catalysts and chromatography. Moreover, 2-thioadenosine was obtained in reliable yield on a 100 g scale.