3’,5’-二氨基脱氧核苷的新合成方法

A New Synthesis Method of 3’,5’-Diaminedeoxynucleoside

以商业化的2＇-脱氧核苷为原料,经过两步Mitsunobu反应得到构型保持的3＇和5＇端叠氮取代的脱氧核苷,并通过一步Staudinger还原反应,以较高收率制备得到构型保持的标题化合物。该方法采用安全性较好的叠氮磷酸二苯酯作为叠氮源来取代叠氮化钠,实现了叠氮化合物的制备,以三苯基膦作为还原剂实现对叠氮的原位还原,避免了强腐蚀性和剧毒易爆原料的使用以及叠氮化合物的分离,以高效、简洁的操作实现了目标分子的制备,为安全高效地大规模生产该类化合物提供了新的方法。

A new synthesis method of 3＇,5＇-diaminedeoxynucleoside was reported by using 2＇-deoxynucleoside as the starting material,two Mitsunobu reaction and one Staudinger reduction was utilized to obtained the configuration maintained 3＇,5＇-diaminedeoxynucleoside.The hydroxyl group on 2＇-deoxynucleoside was transfer to azide group by two subsequent Mitsunobu reaction,with the ribose＇ s configuration unchanged. In our research,the non-explosive diphenylphosphorylazide was utilized as azide source to replace toxic sodium azide,avoiding the use of hazard chemicals.The triphenylphosphine was chosen as reductant to turn azide to amine without the separation of azide containing compounds.The whole process is easy to handle and no toxic or explosive reagents was used,provides us new choice in 3＇,5＇-diaminedeoxynucleosides＇ synthesis.