Stereospecific synthesis of phosphotriesters by using new condensing reagents

以N，5‘-二甲氧基三苯基脱氧腺苷3’-(邻氯苯基)磷酸和N，3‘-二甲氧基三苯基脱氧腺苷为原料，以Deoxyadenylyl-(3’-5‘)-phosphoro-o-chlorophenyl为缩合剂，经脱甲氧基三甲基化反应，立体选择性地合成了具有Sp构型的1-2，4，6-triisopropylbenzene-5-(pyridin-2-yl)tetrazole脱氧腺苷。通过比较两种对应的非对映异构体，确定了该非对映异构体的绝对构型。这两种对映异构体是用常规缩合试剂制备的，并通过硅胶层析分离出来的。这两种非对映异构体在质子磁共振中的核Overhaser效应和圆二色性，只有当这种类型的立体选择性合成的产物以折叠和扩展形式的平衡存在于溶液中时才能被解释。

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.