申请人:——
公开号:US20040158055A1
公开(公告)日:2004-08-12
A process of manufacturing protected nucleosides comprises reacting a nucleoside with a protecting reagent in the presence of a regioselective activator to produce a regioselectively protected nucleoside. In some embodiments of the inventive method, an optionally substituted trityl or optionally substituted pixyl group is selectively added to the 5′-O-position of a nucleoside in the presence of lutidine as activator or activator/solvent. The inventive method results in improved selectivity of the 5′-O-position over the 3′-O-position, thereby improving overall product yield and purity, and permitting simplified purification protocols, in some cases obviating the need for chromatography to produce a purified protected nucleoside suitable for automated synthesis of oligonucleotides, such as primers, probes and antisense molecules.
制造受保护核苷的过程包括在具有区域选择性活化剂的存在下,将核苷与保护试剂反应,以产生区域选择性受保护核苷。在本发明方法的一些实施例中,可选择地将一个可选取代的三苯甲基或可选择地取代的哌啶基团选择性地添加到核苷的5'-O-位置,同时存在卢替啶作为活化剂或活化剂/溶剂。这种创新方法导致了对5'-O-位置的选择性提高,从而提高了整体产物产量和纯度,并允许简化的纯化方案,在某些情况下,无需色谱法即可生产适用于寡核苷酸的自动合成的纯化受保护核苷,例如引物、探针和反义分子。