申请人:——
公开号:US20030191304A1
公开(公告)日:2003-10-09
The present invention relates to improved methods for the preparation of nucleoside phosphoramidites and oligonucleotides. In one aspect, the methods of the invention are used to prepare phosphitylating reagents using pyridinium salts as activators. In a further aspect, the methods of the invention are used to prepare internucleoside linkages using activators which include at least one pyridinium salt and at least one substituted imidazole. In a further aspect, methods are provided preparation of internucleoside linkages between nucleosides having 2′-substituents using imidazolium or benzimidazolium salts as an activator. In a further aspect, methods are provided preparation of internucleoside linkages between nucleosides having bioreversible protecting group that confers enhanced chemical and biophysical properties, without exocyclic amine protection, using imidazolium or benzimidazolium salts as an activator.
本发明涉及改进的核苷酸磷酰胺和寡核苷酸制备方法。在一个方面,本发明的方法用于使用吡啶盐作为活化剂制备磷酸化试剂。在进一步的方面,本发明的方法用于使用至少一种吡啶盐和至少一种取代咪唑作为活化剂制备核苷酸间连接。在另一个方面,提供了一种方法,用于使用咪唑盐或苯并咪唑盐作为活化剂,制备具有2'-取代基的核苷酸之间的核苷酸间连接。在另一个方面,提供了一种方法,用于使用咪唑盐或苯并咪唑盐作为活化剂,在不进行外环胺保护的情况下,制备具有生物可逆保护基的核苷酸之间的核苷酸间连接,从而使其具有增强的化学和生物物理性质。