Rozners E, Westman E, Strömberg R
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, Sweden.
Nucleic Acids Res. 1994 Jan 11;22(1):94-9. doi: 10.1093/nar/22.1.94.
A number of different protecting groups were compared with respect to their usefulness for protection of 2'-hydroxyl functions during synthesis of oligoribonucleotides using the H-phosphonate approach. The comparison was between the t-butyldimethylsilyl (t-BDMSi), the o-chlorobenzoyl (o-CIBz), the tetrahydropyranyl (THP), the 1-(2-fluorophenyl)-4-methoxypiperidin-4-yl (Fpmp), the 1-(2-chloro-4-methylphenyl)-4-methoxypiperidin-4-yl (Ctmp), and the 1-(2-chloroethoxy)ethyl (Cee) protecting groups. All these groups were tested in synthesis of dodecamers, (Up)11U and (Up)11A, using 5'-O-(4-monomethoxytrityl) or (4,4'-dimethoxytrityl) uridine H-phosphonate building blocks carrying the respective 2'-protection. The performance of the t-BDMSi and o-CIBz derivatives were also compared in synthesis of (Up)19U. The most successful syntheses were clearly those where the t-butyldimethylsilyl group was used. The o-chlorobenzoyl group also gave satisfactory results but seems somewhat limited with respect to synthesis of longer oligomers. The results with all tested acetal derivatives (Fpmp, Ctmp, Cee, THP) were much less successful due to some accompanying cleavage of internucleotidic H-phosphonate functions during removal of 5'-O-protection (DMT).
在使用H-膦酸酯方法合成寡核糖核苷酸的过程中,就2'-羟基官能团保护的有效性对多种不同的保护基团进行了比较。比较的保护基团有叔丁基二甲基甲硅烷基(t-BDMSi)、邻氯苯甲酰基(o-CIBz)、四氢吡喃基(THP)、1-(2-氟苯基)-4-甲氧基哌啶-4-基(Fpmp)、1-(2-氯-4-甲基苯基)-4-甲氧基哌啶-4-基(Ctmp)和1-(2-氯乙氧基)乙基(Cee)保护基团。所有这些基团都在十二聚体(Up)11U和(Up)11A的合成中进行了测试,使用携带相应2'-保护基的5'-O-(4-单甲氧基三苯甲基)或(4,4'-二甲氧基三苯甲基)尿苷H-膦酸酯砌块。t-BDMSi和o-CIBz衍生物在(Up)19U的合成中的性能也进行了比较。最成功的合成显然是使用叔丁基二甲基甲硅烷基的那些。邻氯苯甲酰基也给出了令人满意的结果,但在较长寡聚物的合成方面似乎有些受限。由于在去除5'-O-保护基(DMT)过程中一些核苷酸间H-膦酸酯官能团伴随裂解,所有测试的缩醛衍生物(Fpmp、Ctmp、Cee、THP)的结果都不太成功。