Antimony salt-promoted cyclization facilitating on-DNA syntheses of dihydroquinazolinone derivatives and its applications

Nie, Qigui; Sun, Jie; Fang, Xianfu; He, Xun; Xiong, Feng; Zhang, Gong; Li, Yangfeng; Li, Yizhou

doi:10.1016/j.cclet.2023.108132

Cited by 18 publications

(6 citation statements)

References 66 publications

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“…The DEL technology, based on DNA-small molecule bioconjugates, has emerged as a promising high-throughput drug discovery platform to obtain bioactive compounds of target proteins and a wide range of other biomacromolecules in both industrial and academic realms, evidenced by the generation of several clinical candidates. − By combining the advantage of combinatorial chemical synthesis with the convenience of genetic barcoding, DEL allows the systematic and high-throughput implementation of hundreds of reactions in parallel. A structurally diverse DEL is crucial for the advancement of hit identification, which calls for the development of new DNA-compatible reactions. − Logically, the DEL demonstrates mutual reciprocity with biocompatible conjugation reaction discovery. On one side, harnessing DNA-compatible synthetic methodologies for DEL synthesis significantly facilitates the creation of chemically diverse combinatorial libraries.…”

Section: Results and Discussionmentioning

confidence: 99%

Unexpected Cyclization Product Discovery from the Photoinduced Bioconjugation Chemistry between Tetrazole and Amine

Zhang,

Liu,

et al. 2024

J. Am. Chem. Soc.

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Bioconjugation chemistry has emerged as a powerful tool for the modification of diverse biomolecules under mild conditions. Tetrazole, initially proposed as a bioorthogonal photoclick handle for 1,3-dipolar cyclization with alkenes, was later demonstrated to possess broader photoreactivity with carboxylic acids, serving as a versatile bioconjugation and photoaffinity labeling probe. In this study, we unexpectedly discovered and validated the photoreactivity between tetrazole and primary amine to afford a new 1,2,4-triazole cyclization product. Given the significance of functionalized Nheterocycles in medicinal chemistry, we successfully harnessed the serendipitously discovered reaction to synthesize both pharmacologically relevant DNA-encoded chemical libraries (DELs) and small molecule compounds bearing 1,2,4-triazole scaffolds. Furthermore, the mild reaction conditions and stable 1,2,4-triazole linkage found broad application in photoinduced bioconjugation scenarios, spanning from intramolecular peptide macrocyclization and templated DNA reaction cross-linking to intermolecular photoaffinity labeling of proteins. Triazole cross-linking products on lysine side chains were identified in tetrazole-labeled proteins, refining the comprehensive understanding of the photo-cross-linking profiles of tetrazole-based probes. Altogether, this tetrazoleamine bioconjugation expands the current bioconjugation toolbox and creates new possibilities at the interface of medicinal chemistry and chemical biology.

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Section: Results and Discussionmentioning

confidence: 99%

Unexpected Cyclization Product Discovery from the Photoinduced Bioconjugation Chemistry between Tetrazole and Amine

Zhang,

Liu,

et al. 2024

J. Am. Chem. Soc.

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“…In order to improve the success rate of DEL selection, forging DELs containing focused pharmacophores is of great value. 6 The modes of constructing pharmacophores in DELs can be divided into two major categories, including the decoration of a pharmacophore on a modifiable skeleton 7 and direct fusion of multiple building blocks (BBs) to assemble pharmaceutically privileged scaffolds, 8 such as N-heterocycles (pyrazoline, 8 c benzodiazepine, 8 d etc .) assembled by multi-component reactions (MCRs).…”

Section: Introductionmentioning

confidence: 99%

DNA-compatible synthesis of enaminones via amination of allenic ketones

et al. 2023

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“…Furthermore, utilizing endogenous handles for cyclization can eliminate the incorporation of nonessential components into the macrocycles . Moreover, the motifs formed by cyclization chemistry also could increase the molecular diversity in DNA-linked compounds . Consequently, continued exploration and development of new on-DNA cyclization strategies are essential to advance the field of DNA-encoded libraries.…”

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confidence: 99%

Macrocyclizing DNA-Linked Peptides via Three-Component Cyclization and Photoinduced Chemistry

et al. 2023

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While DNA-encoded macrocyclic libraries have gained substantial attention and several hit compounds have been identified from DNA-encoded library technology, efficient on-DNA macrocyclic methods are also required to construct DNA-linked libraries with a high degree of cyclization and DNA integrity. In this paper, we reported a set of on-DNA methodologies, including the use of an OPA-mediated three-component cyclization with native handles of amino acids and photoredox chemistries. These chemistries proceed smoothly under mild conditions in good to excellent conversions, successfully generating novel isoindole, isoindoline, indazolone, and bicyclic scaffolds.

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Antimony salt-promoted cyclization facilitating on-DNA syntheses of dihydroquinazolinone derivatives and its applications

Cited by 18 publications

References 66 publications

Unexpected Cyclization Product Discovery from the Photoinduced Bioconjugation Chemistry between Tetrazole and Amine

Unexpected Cyclization Product Discovery from the Photoinduced Bioconjugation Chemistry between Tetrazole and Amine

DNA-compatible synthesis of enaminones via amination of allenic ketones

Macrocyclizing DNA-Linked Peptides via Three-Component Cyclization and Photoinduced Chemistry

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