Nature chemistry最新文献_第10页

Discovery of a fluorinated macrobicyclic antibiotic through chemical synthesis 通过化学合成发现一种氟化大双环抗生素。

IF 19.2 1区化学

Nature chemistry Pub Date : 2025-03-07 DOI: 10.1038/s41557-025-01738-7

Ben I. C. Tresco, Kelvin J. Y. Wu, Antonio Ramkissoon, Elena V. Aleksandrova, Michael Purdy, Dominic N. Y. See, Richard Y. Liu, Yury S. Polikanov, Andrew G. Myers

{"title":"Discovery of a fluorinated macrobicyclic antibiotic through chemical synthesis","authors":"Ben I. C. Tresco, Kelvin J. Y. Wu, Antonio Ramkissoon, Elena V. Aleksandrova, Michael Purdy, Dominic N. Y. See, Richard Y. Liu, Yury S. Polikanov, Andrew G. Myers","doi":"10.1038/s41557-025-01738-7","DOIUrl":"10.1038/s41557-025-01738-7","url":null,"abstract":"The emergence of bacterial antimicrobial resistance threatens to undermine the utility of antibiotic therapy in medicine. This threat can be addressed, in part, by reinventing existing antibiotic classes using chemical synthesis. Here we present the discovery of BT-33, a fluorinated macrobicyclic oxepanoprolinamide antibiotic with broad-spectrum activity against multidrug-resistant bacterial pathogens. Structure–activity relationships within the macrobicyclic substructure reveal structural features that are essential to the enhanced potency of BT-33 as well as its increased metabolic stability relative to its predecessors clindamycin, iboxamycin and cresomycin. Using X-ray crystallography, we determine the structure of BT-33 in complex with the bacterial ribosome revealing that its fluorine atom makes an additional van der Waals contact with nucleobase G2505. Through variable-temperature 1H NMR experiments, density functional theory calculations and vibrational circular dichroism spectroscopy, we compare macrobicyclic homologues of BT-33 and a C7 desmethyl analogue and find that the C7 methyl group of BT-33 rigidifies the macrocyclic ring in a conformation that is highly preorganized for ribosomal binding. Antibiotic resistance can be addressed by reinventing classes of antibiotics through chemical synthesis. Here BT-33—a fully synthetic antibiotic—affords broad-spectrum activity against the bacterial ribosome. X-ray crystallography, theoretical calculations and structure–activity relationship studies reveal the structural features that contribute to the enhanced antibacterial activity and metabolic stability of BT-33.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 4","pages":"582-589"},"PeriodicalIF":19.2,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preparing and publishing a paper 准备和发表论文

IF 19.2 1区化学

Nature chemistry Pub Date : 2025-03-06 DOI: 10.1038/s41557-025-01759-2

Shira Joudan

引用次数: 0

The phosphate of life 生命的磷酸盐

IF 19.2 1区化学

Nature chemistry Pub Date : 2025-03-06 DOI: 10.1038/s41557-025-01758-3

Elena De Vita, Rebecca Page

引用次数: 0

Preparation, separation and storage of N-monofluoromethyl amides and carbamates n -单氟甲基酰胺和氨基甲酸酯的制备、分离和储存

IF 19.2 1区化学

Nature chemistry Pub Date : 2025-03-04 DOI: 10.1038/s41557-025-01767-2

Min Tao, Jiasheng Qian, Linbei Deng, David M. Wilson, Xiangsong Zhang, Jianbo Liu

{"title":"Preparation, separation and storage of N-monofluoromethyl amides and carbamates","authors":"Min Tao, Jiasheng Qian, Linbei Deng, David M. Wilson, Xiangsong Zhang, Jianbo Liu","doi":"10.1038/s41557-025-01767-2","DOIUrl":"10.1038/s41557-025-01767-2","url":null,"abstract":"N-monofluoromethyl (N-CH2F) amides, combining amide and monofluoromethyl motifs, represent a practical modification of the amide bond that can mimic N-CH3 amides. Despite the potential value in transforming peptides and peptidomimetics with N-CH2F, the very existence of this structure has been controversial. Here we report the preparation of N-CH2F amides and carbamates via simple and robust chemical methods. The syntheses of N-CH2F amides were achieved via successive acylation and fluorination of imines and directly used in the modification of drugs, peptides and heteroaryl amides without racemization or epimerization. The use of triethylamine is the key to the separation of N-CH2F amides. The stability of nine structurally diverse N-CH2F amides was tested in eight different media, showing that most compounds remained 60–100% intact for 24 h. The monofluoromethyl (CH2F) motif is valuable as it can mimic CH3 and CH2OH motifs frequently found in bioactive molecules, but the synthesis of N-CH2F amides is challenging. Now the synthesis of numerous N-CH2F amides has been achieved via successive acylation and fluorination of imines, enriching pathways for N-methylation of biomolecules.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 4","pages":"532-540"},"PeriodicalIF":19.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Direct stereoselective C(sp3)–H alkylation of saturated heterocycles using olefins 使用烯烃对饱和杂环进行直接立体选择性 C(sp3)-H 烷基化反应。

IF 19.2 1区化学

Nature chemistry Pub Date : 2025-02-28 DOI: 10.1038/s41557-025-01747-6

Zhijun Zhou, Yang Ke, Rui Miao, Fen Hu, Xiaoqin Wang, Yuanyuan Ping, Sheng Xu, Wangqing Kong

{"title":"Direct stereoselective C(sp3)–H alkylation of saturated heterocycles using olefins","authors":"Zhijun Zhou, Yang Ke, Rui Miao, Fen Hu, Xiaoqin Wang, Yuanyuan Ping, Sheng Xu, Wangqing Kong","doi":"10.1038/s41557-025-01747-6","DOIUrl":"10.1038/s41557-025-01747-6","url":null,"abstract":"Despite cross-coupling strategies that enable the functionalization of aromatic heterocycles, the enantioselective C(sp3)–H alkylation of readily available saturated hydrocarbons to construct C(sp3)–C(sp3) bonds remains a formidable challenge. Here we describe a nickel-catalysed enantioselective C(sp3)–H alkylation of saturated heterocycles using olefins, providing an efficient strategy for the stereoselective construction of C(sp3)–C(sp3) bonds. Using readily available and stable olefins and simple saturated nitrogen and oxygen heterocycles as prochiral nucleophiles, the coupling reactions proceed under mild conditions and exhibit broad scope and high functional group tolerance. Furthermore, the enantio- and diastereoselective C(sp3)–H alkylation of saturated hydrocarbons with alkenyl boronates has been achieved, enabling the synthesis of versatile alkyl boronates containing 1,2-adjacent C(sp3) stereocentres. Application of this approach to the late-stage modification of natural products and drugs, as well as to the enantioselective synthesis of a range of chiral building blocks and natural products, is demonstrated. The enantioselective C(sp3)–H alkylation of saturated hydrocarbons to construct C(sp3)–C(sp3) bonds is challenging. Now a nickel-catalysed enantioselective C(sp3)–H alkylation of saturated heterocycles using olefins has been developed. The enantio- and diastereoselective C(sp3)–H alkylation of saturated hydrocarbons with alkenyl boronates has also been achieved to give alkyl boronates containing 1,2-adjacent C(sp3) stereocentres.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 3","pages":"344-355"},"PeriodicalIF":19.2,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stereoselective alkylation of saturated heterocycles 饱和杂环的立体选择性烷基化。

IF 19.2 1区化学

Nature chemistry Pub Date : 2025-02-28 DOI: 10.1038/s41557-025-01754-7

Yan Li, Xi Lu

引用次数: 0

Flexible interaction patches lead to building blocks with fluctuating valency 灵活的交互补丁导致构建块具有波动的价

IF 19.2 1区化学

Nature chemistry Pub Date : 2025-02-27 DOI: 10.1038/s41557-025-01756-5

Tine C. M. Stevens, Pepijn G. Moerman

引用次数: 0

Enantioselective photocatalytic synthesis of bicyclo[2.1.1]hexanes as ortho-disubstituted benzene bioisosteres with improved biological activity 对映选择性光催化合成邻二取代苯生物同位酯[2.1.1

IF 21.8 1区化学

Nature chemistry Pub Date : 2025-02-25 DOI: 10.1038/s41557-025-01746-7

Pablo Garrido-García, Irene Quirós, Paula Milán-Rois, Silvia Ortega-Gutiérrez, Mar Martín-Fontecha, Luis A. Campos, Álvaro Somoza, Israel Fernández, Thomas Rigotti, Mariola Tortosa

{"title":"Enantioselective photocatalytic synthesis of bicyclo[2.1.1]hexanes as ortho-disubstituted benzene bioisosteres with improved biological activity","authors":"Pablo Garrido-García, Irene Quirós, Paula Milán-Rois, Silvia Ortega-Gutiérrez, Mar Martín-Fontecha, Luis A. Campos, Álvaro Somoza, Israel Fernández, Thomas Rigotti, Mariola Tortosa","doi":"10.1038/s41557-025-01746-7","DOIUrl":"https://doi.org/10.1038/s41557-025-01746-7","url":null,"abstract":"1,5-Disubstituted bicyclo[2.1.1]hexanes are bridged scaffolds with well-defined exit vectors that are becoming increasingly popular building blocks in medicinal chemistry because they are saturated bioisosteres of ortho-substituted phenyl rings. Here we have developed a Lewis-acid-catalysed [2 + 2] photocycloaddition to obtain these motifs as enantioenriched scaffolds, providing an efficient approach for their incorporation in a variety of drug analogues. Retention of the biological activity of the bicyclo[2.1.1]hexane-containing analogues in the specific proteins targeted by the original drugs has confirmed the suitability of this moiety to serve as a bioisostere of ortho-substituted phenyl rings. Moreover, we have studied the potential of the different enantiomers of the drug analogues to selectively induce cytotoxicity in a panel of tumour cell lines, observing markedly differential effects for the two enantiomers and a substantial improvement over the corresponding sp2-based drugs. This showcases that the control of the absolute configuration and tridimensionality of the drug analogue has a large impact on its biological properties.<figure></figure>","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"18 1","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Photomediated aliphatic C–H functionalization 脂族C-H功能化

IF 19.2 1区化学

Nature chemistry Pub Date : 2025-02-24 DOI: 10.1038/s41557-025-01755-6

Tin V. T. Nguyen, Jerome Waser

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Hydrogen transfer pathway controls selectivity in electrocatalytic CO2 reduction 氢转移途径控制电催化CO2还原的选择性

IF 19.2 1区化学

Nature chemistry Pub Date : 2025-02-24 DOI: 10.1038/s41557-025-01761-8

Chengzhang Wan, Joel W. Ager, Yu Huang

引用次数: 0