The process for the synthesis of modified P-chiral nucleotide analogues of general formula (1) in the form of pure diastereomer possessing preselected configuration at the P-atom, where: R1 stands for a protecting group, preferably 4,4'-dimethoxytrityl (DMT), 9-phenylxanthene-9-ol (Px) or trialkylsilyl group; R2 is a hydrogen atom, protected hydroxyl group, halogen, chloroalkyl, nitrile, azide, protected amine group, perfluoroalkyl (containing up to four carbon atoms), perfluoroalkoxyl (containing up to four carbon atoms and up to nine fluorine or chlorine atoms), alkoxyalkyl, vinyl, ethynyl, OQ1, SQ1, NHQ1, where Q1 stands for alkyl (C1-C4), aryl (C6-C12), alkenyl (C3-C12) or alkynyl (C3-C12); B stands for a purine or pyrimidine base (appropriately protected at nitrogen atoms if necessary); Z is selected from Q1 or vinyl, ethynyl, aminomethyl or aminoethyl substituents; X means an oxygen, sulfur or selenium atom; Rx is a protecting group, preferably aroyl, acyl, alkoxycarbonyl, benzenesulfonic, alkyl, trialkylsilyl group or the next unit of elongated oligonucleotide chain. Antisense oligonucleotides containing P-chiral compounds of general formula (1) have enhanced hybridization and transporting properties.
展开▼
机译：以纯非对映异构体的形式在P原子上具有预选构型的通式（1）修饰的P-手性核苷酸类似物的合成方法，其中：R1代表保护基，优选4,4'-二甲氧基三苯甲基（ DMT），9-苯基x吨-9-醇（Px）或三烷基甲硅烷基; R 2是氢原子，被保护的羟基，卤素，氯烷基，腈，叠氮化物，被保护的胺基，全氟烷基（最多包含四个碳原子），全氟烷氧基（最多包含四个碳原子和最多九个氟或氯原子），烷氧基烷基，乙烯基，乙炔基，OQ1，SQ1，NHQ1，其中Q1代表烷基（C1-C4），芳基（C6-C12），烯基（C3-C12）或炔基（C3-C12）; B代表嘌呤或嘧啶碱基（必要时在氮原子上适当保护）; Z选自Q 1或乙烯基，乙炔基，氨甲基或氨乙基取代基; X表示氧，硫或硒原子; Rx是保护基，优选芳基，酰基，烷氧基羰基，苯磺酸基，烷基，三烷基甲硅烷基或细长的寡核苷酸链的下一个单元。含有通式（1）的P-手性化合物的反义寡核苷酸具有增强的杂交和转运特性。
展开▼
