Department of Chemistry, McGill University, Montréal, Quebec H3A 0B8, Canada.
Department of Chemistry, McGill University, Montréal, Quebec H3A 0B8, Canada.
Bioorg Med Chem Lett. 2014 May 1;24(9):2146-9. doi: 10.1016/j.bmcl.2014.03.032. Epub 2014 Mar 20.
We have investigated the cleavage rates of various protecting groups for the exocyclic amine of cytosine, adenine, and guanine bases. Specifically, deprotection of N-benzoyl (Bz), N-acetyl (Ac), N-isobutyryl (iBu), N-phenoxyacetyl (PAC) and N-tert-butylphenoxyacetyl (tBPAC) groups from 2'-deoxyribonucleosides was effected under various cleavage conditions and the rates of cleavage (half-lives) were determined. Aqueous methylamine cleaves all of the examined protecting groups from the exocyclic amine the fastest among the six methods used. Ethanolic ammonia showed the highest selectivity between standard protecting groups (Ac, Bz, iBu) and fast-deprotecting groups (PAC, tBPAC). Under ammonia conditions, it was possible to cleave PAC and tBPAC rapidly and selectively in 2h, while still retaining the large majority of the acetyl, benzoyl and isobutyryl groups. The results of this study allowed us to perform mild and complete deprotection of an oligoribonucleotide while still attached to the support with a light labile linker. This procedure simplifies and speeds up post-synthesis processing of the RNA chain and offers a new route to the synthesis of sensitive oligonucleotide derivatives on solid supports.
我们研究了胞嘧啶、腺嘌呤和鸟嘌呤碱基中环外氨基的各种保护基团的裂解速率。具体来说，在各种裂解条件下，从 2'-脱氧核苷中脱去 N-苯甲酰基（Bz）、N-乙酰基（Ac）、N-异丁酰基（iBu）、N-苯氧乙酰基（PAC）和 N-叔丁基苯氧乙酰基（tBPAC）基团，并确定了裂解速率（半衰期）。在六种方法中，水合甲胺是最快脱除环外氨基上所有被考察保护基的试剂。乙醇氨在标准保护基（Ac、Bz、iBu）和快速脱保护基（PAC、tBPAC）之间显示出最高的选择性。在氨条件下，在 2 小时内可以快速和选择性地裂解 PAC 和 tBPAC，同时仍然保留大部分乙酰基、苯甲酰基和异丁酰基。这项研究的结果使我们能够在与轻不稳定连接子连接的情况下温和且完全地脱除寡核糖核苷酸的保护基。该方法简化并加速了 RNA 链的合成后处理，为在固体载体上合成敏感寡核苷酸衍生物提供了新途径。
