An evaluation of selective deprotection conditions for the synthesis of RNA on a light labile solid support.
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.
Department of Chemistry, McGill University, Montréal, Quebec H3A 0B8, Canada.
Richard A
RA
Johnsson
Department of Chemistry, McGill University, Montréal, Quebec H3A 0B8, Canada.
Jovanka J
JJ
Bogojeski
Department of Chemistry, McGill University, Montréal, Quebec H3A 0B8, Canada. Electronic address: masad.damha@mcgill.ca.
Masad J
MJ
Damha
D000225:Adenine / Q000737:chemistry; D002855:Chromatography, Thin Layer; D003596:Cytosine / Q000737:chemistry; D006147:Guanine / Q000737:chemistry; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D012313:RNA / Q000138:chemical synthesis* / Q000737:chemistry; D014498:Uracil / Q000737:chemistry
D009705:Nucleosides; D009841:Oligonucleotides; D014498:Uracil; D006147:Guanine; D012313:RNA; D003596:Cytosine; D000225:Adenine
Light labile linker; Nucleic acids; Nucleosides; RNA; TLC