Stereospecific synthesis of phosphotriesters by using new condensing reagents

以1-2,4,6-三异丙苯-5-（吡啶-2-基）四氮唑为缩合剂，用N，3'-二二甲氧基三甲基脱氧腺苷- 3'-（邻氯苯基）磷酸与N，3'-二二甲氧基三甲基脱氧腺苷- 3'-（邻氯苯基）磷酸进行缩合，然后进行去二甲氧基三硝基化，立体选择性地合成了Sp构型的脱氧腺苷-(3'-5')磷-邻氯苯基脱氧腺苷。用常规凝聚剂制备的非对映体和硅胶层析分离的非对映体的绝对构型进行了比较，确定了该非对映体的绝对构型。质子磁共振中的核Overhauser效应和这两种非对映异构体的圆二色性只有在这种类型的立体选择合成得到的产物作为折叠和扩展形式的平衡存在于溶液中才能解释。

Deoxyadenylyl-(3'-5')-phosphoro-o-chlorophenyl deoxyadenosine having the Sp configuration was synthesized stereoselectively by condensing N,5'-bis-dimethoxytrityldeoxyadenosine 3'-(o-chlorophenyl)phosphate with N,3'-bis-dimethoxytrityldeoxyadenosine using 1-2,4,6-triisopropylbenzene-5-(pyridin-2-yl)tetrazole as the condensing reagent followed by dedimethoxytritylation. The absolute configuration of this diastereomer was determined spectroscopically by comparison of two corresponding diastereomers which were prepared by using a conventional condensing reagent and isolated by chromatography on silica gel. Their nuclear Overhauser effect in proton magnetic resonances and the circular dichroism of these two diastereoisomers could only be explained if the product obtained by the stereoselective synthesis of this type exist in solution as an equilibrium of folded and extended forms.