A Study on Synthesis and Upscaling of 2′-O-AECM-5-methyl Pyrimidine Phosphoramidites for Oligonucleotide Synthesis

2′-O-(N-(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 la...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kristina Karalė, Martin Bollmark, Rouven Stulz, Dmytro Honcharenko, Ulf Tedebark, Roger Strömberg
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	2′-<i>O</i>-(N-(aminoethyl)carbamoyl)methyl modification phase transfer catalysis (PTC) 5-methyluridine 5-methylcytidine oligonucleotides alkylation Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/567574a25e0b4173a9ab63f4adf01037
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:567574a25e0b4173a9ab63f4adf01037
record_format	dspace
spelling	oai:doaj.org-article:567574a25e0b4173a9ab63f4adf010372021-11-25T18:28:30ZA Study on Synthesis and Upscaling of 2′-<i>O</i>-AECM-5-methyl Pyrimidine Phosphoramidites for Oligonucleotide Synthesis10.3390/molecules262269271420-3049https://doaj.org/article/567574a25e0b4173a9ab63f4adf010372021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6927https://doaj.org/toc/1420-30492′-<i>O</i>-(<i>N</i>-(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<sup>3</sup> 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.Kristina KaralėMartin BollmarkRouven StulzDmytro HoncharenkoUlf TedebarkRoger StrömbergMDPI AGarticle2′-<i>O</i>-(N-(aminoethyl)carbamoyl)methyl modificationphase transfer catalysis (PTC)5-methyluridine5-methylcytidineoligonucleotidesalkylationOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6927, p 6927 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	2′-<i>O</i>-(N-(aminoethyl)carbamoyl)methyl modification phase transfer catalysis (PTC) 5-methyluridine 5-methylcytidine oligonucleotides alkylation Organic chemistry QD241-441
spellingShingle	2′-<i>O</i>-(N-(aminoethyl)carbamoyl)methyl modification phase transfer catalysis (PTC) 5-methyluridine 5-methylcytidine oligonucleotides alkylation Organic chemistry QD241-441 Kristina Karalė Martin Bollmark Rouven Stulz Dmytro Honcharenko Ulf Tedebark Roger Strömberg A Study on Synthesis and Upscaling of 2′-<i>O</i>-AECM-5-methyl Pyrimidine Phosphoramidites for Oligonucleotide Synthesis
description	2′-<i>O</i>-(<i>N</i>-(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<sup>3</sup> 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.
format	article
author	Kristina Karalė Martin Bollmark Rouven Stulz Dmytro Honcharenko Ulf Tedebark Roger Strömberg
author_facet	Kristina Karalė Martin Bollmark Rouven Stulz Dmytro Honcharenko Ulf Tedebark Roger Strömberg
author_sort	Kristina Karalė
title	A Study on Synthesis and Upscaling of 2′-<i>O</i>-AECM-5-methyl Pyrimidine Phosphoramidites for Oligonucleotide Synthesis
title_short	A Study on Synthesis and Upscaling of 2′-<i>O</i>-AECM-5-methyl Pyrimidine Phosphoramidites for Oligonucleotide Synthesis
title_full	A Study on Synthesis and Upscaling of 2′-<i>O</i>-AECM-5-methyl Pyrimidine Phosphoramidites for Oligonucleotide Synthesis
title_fullStr	A Study on Synthesis and Upscaling of 2′-<i>O</i>-AECM-5-methyl Pyrimidine Phosphoramidites for Oligonucleotide Synthesis
title_full_unstemmed	A Study on Synthesis and Upscaling of 2′-<i>O</i>-AECM-5-methyl Pyrimidine Phosphoramidites for Oligonucleotide Synthesis
title_sort	study on synthesis and upscaling of 2′-<i>o</i>-aecm-5-methyl pyrimidine phosphoramidites for oligonucleotide synthesis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/567574a25e0b4173a9ab63f4adf01037
work_keys_str_mv	AT kristinakarale astudyonsynthesisandupscalingof2ioiaecm5methylpyrimidinephosphoramiditesforoligonucleotidesynthesis AT martinbollmark astudyonsynthesisandupscalingof2ioiaecm5methylpyrimidinephosphoramiditesforoligonucleotidesynthesis AT rouvenstulz astudyonsynthesisandupscalingof2ioiaecm5methylpyrimidinephosphoramiditesforoligonucleotidesynthesis AT dmytrohoncharenko astudyonsynthesisandupscalingof2ioiaecm5methylpyrimidinephosphoramiditesforoligonucleotidesynthesis AT ulftedebark astudyonsynthesisandupscalingof2ioiaecm5methylpyrimidinephosphoramiditesforoligonucleotidesynthesis AT rogerstromberg astudyonsynthesisandupscalingof2ioiaecm5methylpyrimidinephosphoramiditesforoligonucleotidesynthesis AT kristinakarale studyonsynthesisandupscalingof2ioiaecm5methylpyrimidinephosphoramiditesforoligonucleotidesynthesis AT martinbollmark studyonsynthesisandupscalingof2ioiaecm5methylpyrimidinephosphoramiditesforoligonucleotidesynthesis AT rouvenstulz studyonsynthesisandupscalingof2ioiaecm5methylpyrimidinephosphoramiditesforoligonucleotidesynthesis AT dmytrohoncharenko studyonsynthesisandupscalingof2ioiaecm5methylpyrimidinephosphoramiditesforoligonucleotidesynthesis AT ulftedebark studyonsynthesisandupscalingof2ioiaecm5methylpyrimidinephosphoramiditesforoligonucleotidesynthesis AT rogerstromberg studyonsynthesisandupscalingof2ioiaecm5methylpyrimidinephosphoramiditesforoligonucleotidesynthesis
_version_	1718411075140976640

A Study on Synthesis and Upscaling of 2′-<i>O</i>-AECM-5-methyl Pyrimidine Phosphoramidites for Oligonucleotide Synthesis

Ejemplares similares