Simplified Oligonucleotide Phosphorus Deprotection Process with Reduced 3-(2-Cyanoethyl) Thymidine Impurities.
Nucleic Acid Ther
; 34(2): 83-89, 2024 04.
Article
em En
| MEDLINE
| ID: mdl-38315742
ABSTRACT
Oligonucleotides have emerged as valuable new therapeutics. Presently, oligonucleotide manufacturing consists in a series of stepwise additions until the full-length product is obtained. Deprotection of the phosphorus backbone before cleavage and deprotection (C&D) by ammonolysis is necessary to control the 3-(2-cyanoethyl) thymidine (CNET) impurity. In this study, we demonstrate that the use of piperazine as a scavenger of acrylonitrile allows phosphorus deprotection and C&D to be combined in a single step. This reduces solvent consumption, processing time, and CNET levels. Additionally, we showed that substitution of piperazine for triethylamine in the phosphorus deprotection step of supported-synthesis leads to reduced reaction times and lower levels of CNET impurities.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligonucleotídeos
/
Fósforo
Idioma:
En
Revista:
Nucleic Acid Ther
Ano de publicação:
2024
Tipo de documento:
Article