On-DNA Alkyne Iodination and Acetylenic Coupling as a Useful Tool for DEL Synthesis.

Bioconjug Chem

Pharmaron (Ningbo) Technology Development Co., Ltd. No. 800 Bin-Hai 4th Road, Hangzhou Bay New Zone, Ningbo, 315336, China.

Published: December 2022

1-Iodoalkynes and 1,3-diynes are versatile chemical intermediates and pharmaceutically valuable ingredients. In this study, copper mediated on-DNA alkyne iodination and Cadiot-Chodkiewicz coupling are developed for the first time. This generates diverse, systematic, and unprecedented topographic structural features, which could be invaluable as molecular recognition agents for drug discovery in DEL screening.

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.bioconjchem.2c00471DOI Listing

Publication Analysis

Top Keywords

on-dna alkyne
8
alkyne iodination
8
iodination acetylenic
4
acetylenic coupling
4
coupling tool
4
tool del
4
del synthesis
4
synthesis 1-iodoalkynes
4
1-iodoalkynes 13-diynes
4
13-diynes versatile
4

Similar Publications

Rhodium-Promoted C-H Activation/Annulation between DNA-Linked Terminal Alkyne and Aromatic Acid: A Finding from the Selection Outcomes.

Org Lett

June 2024

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai 201203, China.

Inspired by previous selection outcomes, we investigated and developed a rhodium-promoted C-H activation/annulation reaction of DNA-linked terminal alkynes and aromatic acids. This reaction exhibits excellent efficiency with high conversions and a broad substrate scope. Most importantly, the unique DEL-compatible conditions provide a better scenario for yielding an isocoumarin scaffold compared to conventional organic reaction conditions, and this newly developed on-DNA method has confirmed its feasibility in preparing DNA-encoded libraries.

View Article and Find Full Text PDF

Synthesis of Functionalized Triazoles on DNA via Azide-Acetonitrile "Click" Reaction.

Org Lett

November 2023

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, P. R. China.

Triazoles are privileged structural motifs that are embedded in a number of molecules with interesting biological activities. In this work, we developed a practical and general synthetic strategy to construct a medicinally important 5-amino-1,2,3-triazole moiety on DNA by coupling DNA-conjugated azides and monosubstituted acetonitriles via azide-acetonitrile "click" reaction. Under mild reaction conditions, this reaction displayed a broad substrate scope.

View Article and Find Full Text PDF

Enolate-Azide [3 + 2]-Cycloaddition Reaction Suitable for DNA-Encoded Library Synthesis.

Bioconjug Chem

August 2023

Shanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai 201210, P. R. China.

The DNA-encoded chemical library (DEL) is a powerful hit selection technique in either basic science or innovative drug discovery. With the aim to circumvent the issue concerning DNA barcode damage in a conventional on-DNA copper-catalyzed azide-alkyne cycloaddition reaction (CuAAC), we have successfully developed the first DNA-compatible enolate-azide [3 + 2] cycloaddition reaction. The merits of this DEL chemistry include metal-free reaction and high DNA fidelity, high conversions and easy operation, broad substrate scope, and ready access to the highly substituted 1,4,5-trisubstituted triazoles.

View Article and Find Full Text PDF

Development of On-DNA Thiophene Synthesis for DEL Construction.

Chem Asian J

August 2023

Pharmaron (Ningbo) Technology Development Co., Ltd., No. 800 Bin-Hai 4th Road, Hangzhou Bay New Zone, Ningbo, 315336, P. R. China.

Thiophene and its substituted derivatives are a highly important class of heterocyclic compounds, with noteworthy applications in pharmaceutical ingredients. In this study, we leverage the unique reactivity of alkynes to generate thiophenes on-DNA, using a cascade iodination, Cadiot-Chodkiewicz coupling and heterocyclization. This approach, tackling on-DNA thiophene synthesis for the first time, generates diverse, and unprecedented structural and chemical features, which could be significant motifs in DEL screening as molecular recognition agents for drug discovery.

View Article and Find Full Text PDF

Micelle-Mediated Sonogashira Coupling for DNA-Encoded Library Synthesis.

Chemistry

July 2023

Cancer Research Horizons Therapeutic Innovation, Newcastle Drug Discovery Group, Chemistry, School of Natural and Environmental Sciences Bedson Building, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.

DNA-Encoded Libraries (DELs) are becoming widely established as a hit identification strategy for drug discovery campaigns. Their successful application relies on the availability and efficiency of the reactions that can be carried out on DNA. These reactions should proceed with high conversion to the desired product and have a broad substrate scope to synthesise chemically diverse and drug-like DELs.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!