Retro-Cope elimination of cyclic alkynes: reactivity trends and rational design of next-generation bioorthogonal reagents DOI Creative Commons
Steven E. Beutick, Song Yu, Laura Orian

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(37), P. 15178 - 15191

Published: Jan. 1, 2024

The retro-Cope elimination reaction between dimethylhydroxylamine (DMHA) and various cyclic alkynes has been quantum chemically explored using DFT at ZORA-BP86/TZ2P. purpose of this study is to understand the role following three unique activation modes on overall reactivity, that (i) additional cycloalkyne predistortion via fused cycles, (ii) exocyclic heteroatom substitution cycloalkyne, (iii) endocyclic cycloalkyne. Trends in reactivity are analyzed explained by strain model (ASM) chemical reactivity. Based our newly formulated design principles, we constructed a priori suite novel bioorthogonal reagents highly reactive towards with DMHA. Our findings offer valuable insights into principles for synthesis.

Language: Английский

Computational Organic Chemistry: The Frontier for Understanding and Designing Bioorthogonal Cycloadditions DOI Creative Commons
Dennis Svatunek

Topics in Current Chemistry, Journal Year: 2024, Volume and Issue: 382(2)

Published: May 10, 2024

Computational organic chemistry has become a valuable tool in the field of bioorthogonal chemistry, offering insights and aiding progression this branch chemistry. In review, I present an overview computational work field, including exploration both primary analysis methods used their application main areas chemistry: (3 + 2) [4 2] cycloadditions. context cycloadditions, detailed studies electronic effects have informed evolution cycloalkyne/1,3-dipole Through techniques, researchers found ways to adjust structure via hyperconjugation enhance reactions without compromising stability. For such as distortion/interaction energy decomposition been beneficial, leading development reactants with improved reactivity creation orthogonal reaction pairs. To conclude, touch upon emerging fields cheminformatics machine learning, which promise play role future discovery optimization.

Language: Английский

Citations

4
Site-Selective Decarbonylative [4+2] Annulation of Carboxylic Acids with Terminal Alkynes by C–C/C–H Activation Strategy and Cluster Catalysis DOI Creative Commons

Mengjie Cen,

Xinyue Ma, Xi Yang

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(48), P. 20346 - 20354

Published: Jan. 1, 2024

A highly site-selective decarbonylative [4 + 2] cyclization of carboxylic acids with terminal alkynes forming naphthalenes is enabled by palladium cluster catalysis.

Language: Английский

Citations

4
Signature of click chemistry in advanced techniques for cancer therapeutics DOI Creative Commons

Sherif S. Ragab

RSC Advances, Journal Year: 2025, Volume and Issue: 15(14), P. 10583 - 10601

Published: Jan. 1, 2025

This review focuses mainly on the signature of click chemistry (CuAAC and SPAAC) in advanced techniques for cancer therapeutics.

Language: Английский

Citations

0
7-Deazapurine and Pyrimidine Nucleoside and Oligonucleotide Cycloadducts Formed by Inverse Diels–Alder Reactions with 3,6-Di(pyrid-2-yl)-1,2,4,5-tetrazine: Ethynylated and Vinylated Nucleobases for Functionalization and Impact of Pyridazine Adducts on DNA Base Pair Stability and Mismatch Discrimination DOI
Somnath Shivaji Chandankar,

Dasharath Kondhare,

Sushma Deshmukh

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(16), P. 11304 - 11322

Published: July 25, 2024

The manuscript reports on 7-deazapurine and pyrimidine nucleoside oligonucleotide cycloadducts formed by the inverse electron demand Diels-Alder (iEDDA) reaction with 3,6-di(pyrid-2-yl)-1,2,4,5-tetrazine. Cycloadducts were constructed from ethynylated vinylated nucleobases. Oligonucleotides synthesized containing iEDDA modifications, impact duplex stability was investigated. reactions performed triple bond side chains. Oxidation not required in these cases as dihydropyridazine intermediates are formed. In contrast, oxidation is necessary for alkenyl compounds. This verified 5-vinyl-2'-deoxyuridine. A diastereomeric mixture of 1,2-dihydropyridazine cycloadduct isolated, characterized, later oxidized. 12-mer oligonucleotides 1,2-pyridazine their precursors hybridized to short DNA duplexes. For that, a series phosphoramidites prepared. duplexes 7-functionalized 7-deazaadenines 5-functionalized pyrimidines display high when spacer units present between nucleobases pyridazine cycloadducts. direct connectivity moiety reported metabolic labeling vinyl nucleosides reduced strongly. bearing linkers without attached 7-deazaadenine nucleobase significantly mismatch formation dC dG.

Language: Английский

Citations

1
Retro-Cope elimination of cyclic alkynes: reactivity trends and rational design of next-generation bioorthogonal reagents DOI Creative Commons
Steven E. Beutick, Song Yu, Laura Orian

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(37), P. 15178 - 15191

Published: Jan. 1, 2024

The retro-Cope elimination reaction between dimethylhydroxylamine (DMHA) and various cyclic alkynes has been quantum chemically explored using DFT at ZORA-BP86/TZ2P. purpose of this study is to understand the role following three unique activation modes on overall reactivity, that (i) additional cycloalkyne predistortion via fused cycles, (ii) exocyclic heteroatom substitution cycloalkyne, (iii) endocyclic cycloalkyne. Trends in reactivity are analyzed explained by strain model (ASM) chemical reactivity. Based our newly formulated design principles, we constructed a priori suite novel bioorthogonal reagents highly reactive towards with DMHA. Our findings offer valuable insights into principles for synthesis.

Language: Английский

Citations

0