A1 Refereed original research article in a scientific journal
Toward a sustainable protection group approach for solid-phase oligonucleotide synthesis employing 5′-O-(2-methoxyisopropyl) protection; 
Authors: Saari, Verneri; Ora, Mikko; Gimenez Molina, Alejandro; Horvath, Andras; Sanghvi, Yogesh S.; Virta, Pasi
Publisher: Royal Society of Chemistry (RSC)
Publication year: 2026
Journal: Organic and Biomolecular Chemistry
Volume: 24
Issue: 29
First page : 6082
Last page: 6091
ISSN: 1477-0520
eISSN: 1477-0539
DOI: https://doi.org/10.1039/d6ob00858e
Publication's open availability at the time of reporting: Open Access
Publication channel's open availability : Partially Open Access publication channel
Web address : https://doi.org/10.1039/d6ob00858e
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/526996114
Self-archived copy's licence: CC BY
Self-archived copy's version: Publisher`s PDF
5′-O-(2-Methoxyisopropyl) (MIP)-protected nucleoside-3′-O-phosphoramidites were synthesized and evaluated as novel building blocks for automated solid-phase oligonucleotide synthesis (SPOS). Activators and additives were screened to establish the optimal conditions for the coupling of the 5′-O-MIP building blocks. Approximately half the amount of the deblocking reagent can be used to remove 5′-O-MIP compared to 5′-O-4,4′-dimethoxytrityl (DMT) with twice the rate for its deprotection. The faster 5′-O-deprotection rate reduced overall acid consumption, while the small-molecule benign byproducts (acetone and methanol) generated via MIP deprotection permit a lower PMI during SPOS. This work potentially leverages the improved design of sustainable strategies for the manufacturing of therapeutic oligonucleotides.
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Funding information in the publication:
Financial support from the Doctoral Programme in Exact Sciences (EXACTUS) is acknowledged.
