An evaluation of selective deprotection conditions for the synthesis of RNA on a light labile solid support

作者：Johnsson Richard A; Bogojeski Jovanka J; Damha Masad J^*

来源：Bioorganic & Medicinal Chemistry Letters, 2014, 24(9): 2146-2149.

DOI：10.1016/j.bmcl.2014.03.032

• Light labile linker
• Nucleosides
• Nucleic acids
• RNA
• TLC

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 2 h, 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.

• 出版日期2014-5-1
• 单位McGill