9-(N-氨基-4-氟甲基-3-吡咯)-2,6-二氯嘌呤的简便合成

Facile Synthesis of 9-(N-Amino-4-fluoromethyl-3-pyrrolidinyl)-2,6-dichloropurine from trans-4-Hydroxy-D-proline

以反-4-羟基-D-脯氨酸为原料,经过6步反应合成了N-(p-硝基苄氧羰基)-反-4-羟基-D-脯氨酸甲酯,它与2,6-二氯嘌呤经过Mitsunobu反应生成N-(p-硝基苄氧羰基)-顺-4-(2,6-二氯-9H-嘌呤基)-D-脯氨酸甲酯,经还原、脱保护、亚硝化、还原等单元反应生成N-氨基-顺-4-(2,6-二氯-9H-嘌呤基)-D-脯氨醇,以2,2-二氟-1,3-二甲基咪唑啉(DFI)为氟化剂进行氟化得9-(N-氨基-4-氟甲基-3-吡咯)-2,6-二氯嘌呤。Mitsunobu反应在室温即可进行,不需深冷等苛刻条件。经红外光谱、质谱、核磁共振测试技术对各化合物结构进行了表征。

A novel and simple procedure for the synthesis of aza-nucleoside by Mitsunobu reaction between N-（p-nitrobenzyloxycarbonyl）-trans-4-hydroxy-D-proline methyl ester obtained from trans-4-hydroxy-L.proline after six-step reaction and 2,6-dichloropurine is described. The azanucleoside is reduced, deprotected, nitrosated, reduced and fluorided by new fluoridizer 2,2-difluoro-1,3-dimethylimidazolidine（DFI）. Mitsunobu reaction could be carried out at ambient temperature. Intermediates and the target compound are characterized by IR, MS, H NMR.