2'--AECM-5-甲基嘧啶磷酰胺的合成及规模化研究用于寡核苷酸合成。
A Study on Synthesis and Upscaling of 2'--AECM-5-methyl Pyrimidine Phosphoramidites for Oligonucleotide Synthesis.
机构信息
Department of Biosciences and Nutrition, Karolinska Institutet, Neo, 141 57 Huddinge, Sweden.
RISE, Department Chemical Process and Pharmaceutical Development, Forskargatan 18, 151 36 Södertälje, Sweden.
出版信息
Molecules. 2021 Nov 17;26(22):6927. doi: 10.3390/molecules26226927.
2'--(-(Aminoethyl)carbamoyl)methyl-modified 5-methyluridine (AECM-MeU) and 5-methylcytidine (AECM-MeC) phosphoramidites are reported for the first time and prepared in multigram quantities. The syntheses of AECM-MeU and AECM-MeC nucleosides are designed for larger scales (approx. 20 g up until phosphoramidite preparation steps) using low-cost reagents and minimizing chromatographic purifications. Several steps were screened for best conditions, focusing on the most crucial steps such as N and/or 2'-OH alkylations, which were improved for larger scale synthesis using phase transfer catalysis (PTC). Moreover, the need of chromatographic purifications was substantially reduced by employing one-pot synthesis and improved work-up strategies.
2'--(-(氨乙基)碳酰胺基)甲基修饰的 5-甲基尿苷（AECM-MeU）和 5-甲基胞苷（AECM-MeC）磷酰胺被首次报道，并以多克数量级制备。AECM-MeU 和 AECM-MeC 核苷的合成设计用于更大规模（约 20 克，直到磷酰胺制备步骤），使用低成本试剂和最小化的色谱纯化。筛选了几个步骤以获得最佳条件，重点关注最关键的步骤，如 N 和/或 2'-OH 烷基化，使用相转移催化（PTC）对其进行了改进，以适应更大规模的合成。此外，通过一锅合成和改进的后处理策略，大大减少了色谱纯化的需求。
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