Stereospecific synthesis of phosphotriesters by using new condensing reagents

以1- 2，4，6-三异丙基苯-5-（吡啶-2-基）四唑为缩合剂，通过N，5 ′-双-二甲氧基三苯甲基脱氧腺苷3 ′-（邻氯苯基）磷酸酯与N，3 ′-双-二甲氧基三苯甲基脱氧腺苷缩合，然后进行脱二甲氧基三苯甲基化，立体选择性地合成了具有Sp构型的脱氧腺苷酰-（3 ′-5 ′）-磷酰-邻氯苯基脱氧腺苷。该非对映异构体的绝对构型通过比较两种相应的非对映异构体来光谱测定，所述两种相应的非对映异构体通过使用常规缩合试剂制备并通过硅胶色谱分离。它们在质子磁共振中的核Overhauser效应和这两种非对映异构体的圆二色性只能解释为如果通过这种类型的立体选择性合成获得的产物作为折叠和延伸形式的平衡存在于溶液中。

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.