A1 Refereed original research article in a scientific journal

Selective Acetalization in Pyridine: A Sustainable 5′-O-(2-Methoxypropyl) Protecting Group in the Synthesis of Nucleic Acid Analogs



Authors: Saari, Verneri; Eerola, Aino; Ora, Mikko; Molina, Alejandro Gimenez; Horvath, Andras; Sanghvi, Yogesh S.; Virta, Pasi

Publisher: AMER CHEMICAL SOC

Publishing place: WASHINGTON

Publication year: 2025

Journal: Organic Letters

Journal acronym: ORG LETT

Volume: 27

Issue: 30

First page : 8251

Last page: 8256

Number of pages: 6

ISSN: 1523-7060

eISSN: 1523-7052

DOI: https://doi.org/10.1021/acs.orglett.5c02400

Web address : https://pubs.acs.org/doi/10.1021/acs.orglett.5c02400

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/499676799


Abstract

A mixture of 2-methoxypropene and an acid catalyst in pyridine results in an efficient 5 '-O-(methoxyisopropyl) (MIP) acetalization of nucleosides, including 2 '-deoxy, 2 '-OH, 2 '-O-methyl, 2 '-O-methoxyethyl (MOE) and 2 '-F-variants, in 44-77% isolated yields. For the reaction mechanism, we propose a pyridinium 2-methoxyprop-2-yl preassociation complex, which improves regioselectivity for the primary (5 '-OH) over secondary (2 '-OH and 3 '-OH) hydroxy groups. The developed protocol makes the 5 '-O-MIP-acetal an attractive protecting group for the sustainable synthesis of nucleosides and oligonucleotides in solution.


Downloadable publication

This is an electronic reprint of the original article.
This reprint may differ from the original in pagination and typographic detail. Please cite the original version.

Funding information in the publication: 
The financial support from the Doctoral Programme in Exact Scienses (EXACTUS) and University of Turku Foundation is acknowledged.


Last updated on 2025-03-09 at 07:04