Evidence map›Paper›PMID 40788029›Full record

ArticleAngewandte Chemie (International ed. in English)2025

Rapid Synthesis and Diversification of Thymine-Containing Bridged Nucleic Acids Through Cascade Cyclization Reactions.

Cohan Huxley, Ethan Fung, Bara Singh, Guillermo Caballero-García, Garrett Muir, Steven M Silverman, Louis-Charles Campeau, Robert Britton

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Cohan Huxley *Department of Chemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
Ethan Fung *Department of Chemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
Bara SinghDepartment of Chemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
Guillermo Caballero-GarcíaDepartment of Chemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
Garrett MuirDepartment of Chemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
Steven M SilvermanDepartment of Process Research and Development, Merck & Co., Inc., Rahway, NJ, 07065, USA.
Louis-Charles CampeauDepartment of Process Research and Development, Merck & Co., Inc., Rahway, NJ, 07065, USA.
Robert BrittonDepartment of Chemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.ORCID 0000-0002-9335-0047

Funding

Consortium de Recherche BiopharmaceutiqueNatural Sciences and Engineering Research Council 2019-064680
6 · The paper itself

Abstract

Bridged nucleic acids (BNAs) are nucleoside analogues (NAs) in which the 2'-alcohol is linked to the C4'-position on ribose. In oligonucleotide therapeutics (ONTs), BNAs can impart beneficial properties, including enhanced stability, duplex melting temperatures, and tissue half-lives. However, their lengthy syntheses challenge medicinal chemistry efforts and larger-scale production. Here we demonstrate that a wide range of BNAs can be produced with various locking ring sizes and substitution patterns from a common thymine-containing aldol product through cascade cyclization processes. Critically, several clinically relevant BNAs are now made available in as little as 3-5 steps. We expect these strategies will inspire and support medicinal and process chemistry efforts in this critical area for ONTs.

Indexed as

Nucleic AcidsThymineCyclizationNucleic AcidsThymineCascade cyclizationDe novo synthesisLocked nucleic acidsNucleosidesStereoselective synthesis

Identifiers

PMID40788029
PMCPMC12455439

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.