Nature synthesis最新文献_第6页

In-brain synthesis of receptor-based protease sensors by coupling ligand-directed chemistry and click chemistry 结合配体导向化学和点击化学在脑内合成基于受体的蛋白酶传感器

IF 2

Nature synthesis Pub Date : 2025-06-02 DOI: 10.1038/s44160-025-00815-6

Seiji Sakamoto, Kazuki Shiraiwa, Mengchu Wang, Mamoru Ishikawa, Hiroshi Nonaka, Itaru Hamachi

{"title":"In-brain synthesis of receptor-based protease sensors by coupling ligand-directed chemistry and click chemistry","authors":"Seiji Sakamoto, Kazuki Shiraiwa, Mengchu Wang, Mamoru Ishikawa, Hiroshi Nonaka, Itaru Hamachi","doi":"10.1038/s44160-025-00815-6","DOIUrl":"10.1038/s44160-025-00815-6","url":null,"abstract":"The chemical modification of natural proteins in living systems is highly desirable as cutting-edge research at the chemistry–biology interface. Recent advances in bio-orthogonal protein modification have enabled the production of chemically functionalized proteins in cultured cell systems. However, a limited number of methods are applicable in vivo because of the complexity of the three-dimensional constructs of living systems with diverse, heterogeneous cell populations and flow systems filled with tissue fluids. Here we report a genetic-engineering-free method to modify receptor proteins with various probes in the living mouse brain by combining in-brain ligand-directed chemistry with bio-orthogonal click chemistry, and propose a chemical guideline for the reaction design. The rapid and selective tethering of a set of fluorescent peptides to AMPA-type glutamate receptors allowed the synthesis of receptor-based fluorescent sensors. These probes enabled mapping of the activity of matrix metalloproteinase-9 proximal to AMPA-type glutamate receptors in the living brain to be realized with high spatial resolution. The complexity of living systems makes methods for chemically functionalizing proteins in vivo rare. Here, a genetic-engineering-free method to modify receptor proteins with various probes in the live mouse brain is reported by combining ligand-directed chemistry with click chemistry. This method enables the synthesis of receptor-based fluorescent sensors.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"4 9","pages":"1128-1140"},"PeriodicalIF":20.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44160-025-00815-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chirality retention in Friedel–Crafts spiroannulation for iterative synthesis of spiro-bridged conjugated carbocycles 旋桥共轭碳环迭代合成中Friedel-Crafts旋环的手性保持

IF 2

Nature synthesis Pub Date : 2025-06-02 DOI: 10.1038/s44160-025-00817-4

Xingwen Pu, Yi Lu, Zhonghao Zhou, Yudong Yang, Cheng Zhang, Peiyuan Yu, Yong Sheng Zhao, Jingbo Lan, Jingsong You

{"title":"Chirality retention in Friedel–Crafts spiroannulation for iterative synthesis of spiro-bridged conjugated carbocycles","authors":"Xingwen Pu, Yi Lu, Zhonghao Zhou, Yudong Yang, Cheng Zhang, Peiyuan Yu, Yong Sheng Zhao, Jingbo Lan, Jingsong You","doi":"10.1038/s44160-025-00817-4","DOIUrl":"10.1038/s44160-025-00817-4","url":null,"abstract":"The formation of chiral organic molecules from Friedel–Crafts reactions of chiral alcohols has been deemed impractical due to racemization via carbocation formation. Here we demonstrate the preservation of stereochemistry in intramolecular Friedel–Crafts alkylation reactions, expanding the boundaries of accessible chiral chemistry. Mechanistic investigations show that the retention of stereochemistry stems from the chirality memory of transient, axially chiral carbocation intermediates. This finding allows the synthesis of axially chiral spirocarbon-bridged conjugated carbocycles. Leveraging a rhodium-catalysed regioselective C–H activation–annulation approach, the reaction of thiobenzamide with phenylethynyl tertiary alcohol is a crucial step in expanding the spiro-bridged skeleton. We used this approach to develop an iterative synthetic sequence to construct enantiopure spirocarbon-bridged pure-hydrocarbon oligo(trans-stilbene) compounds. Notably, in the concluding step of the iterative synthesis, all chiral tertiary alcohol units undergo a stereospecific one-shot conversion to form multiple spirocyclic structures, resembling a ‘zipping up’ process. This synthetic strategy facilitates both the longitudinal and lateral extension of spiro-bridged conjugated structures, with promising applications in circularly polarized lasers. A strategy that preserves stereochemistry in intramolecular Friedel–Crafts alkylation is reported. An iterative synthetic approach to extend spiro-bridged molecular skeletons via C–H activation–annulation is developed, where the stereoretentive one-shot conversion to form multiple spirocarbon-bridged carbocycles resembles a ‘zipping up’ process.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"4 10","pages":"1247-1257"},"PeriodicalIF":20.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Publisher Correction: Allosteric regulation in metal–organic cages 出版者更正：金属有机笼的变构调节

IF 2

Nature synthesis Pub Date : 2025-05-27 DOI: 10.1038/s44160-025-00827-2

Yuchong Yang, Yuyin Du, Andrew W. Heard, Jonathan R. Nitschke

引用次数: 0

Nickel-catalysed deuteration of benzylic C(sp3)–H bonds using D2O 镍催化D2O对苯基C(sp3) -H键的氘化反应

IF 2

Nature synthesis Pub Date : 2025-05-22 DOI: 10.1038/s44160-025-00816-5

Feiyu Qiu, Lingyun Yang, Yachun Wang, Yuan Gao, Yi Chen, Aiwen Lei, Wu Li

{"title":"Nickel-catalysed deuteration of benzylic C(sp3)–H bonds using D2O","authors":"Feiyu Qiu, Lingyun Yang, Yachun Wang, Yuan Gao, Yi Chen, Aiwen Lei, Wu Li","doi":"10.1038/s44160-025-00816-5","DOIUrl":"10.1038/s44160-025-00816-5","url":null,"abstract":"Hydrogen isotope exchange, which can directly introduce deuterium without the need to pre-functionalize starting materials and without substantially altering the structure of molecules, is the most efficient method for deuterium incorporation. Here we present a heterogeneous nickel-catalysed deuteration of benzylic positions in alkylarenes and methylarenes using D2O as a deuterium source. For this transformation, we developed a Ni–H2–D2O system that enables H–D exchange of benzylic positions. A nitrogen-containing precursor has a substantial influence on the particle size of the nickel nanoparticles and volcano-type curves concerning the activity in the catalyst. This H–D exchange reaction shows broad substrate scope and good functional group tolerance. Deuterated building blocks, including representative drugs with high deuterium incorporation, were obtained using inexpensive and easy-to-handle D2O. Mechanistic studies indicated that H2 was essential for the isotope exchange process. We envision that such metal–H2–D2O systems could be applied in more catalytic reactions for the preparation of deuterium-labelled compounds. A heterogeneous nickel-catalysed deuteration reaction of benzylic C(sp3)–H bonds in alkylarenes and methylarenes using D2O is developed. Such metal–H2–D2O systems could be extended to other catalytic reactions for the preparation of deuterium-labelled compounds in the future.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"4 9","pages":"1141-1150"},"PeriodicalIF":20.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of chiral difluoromethyl cyclopropanes through desymmetric difluoromethylation of cyclopropenes enabled by enantioselective copper catalysis 通过对映选择性铜催化环丙烯的非对称二氟甲基化合成手性二氟甲基环丙烷。

IF 2

Nature synthesis Pub Date : 2025-05-22 DOI: 10.1038/s44160-025-00809-4

Decai Ding, Su Chen, Lingfeng Yin, Wei-Ting Ou, Jeanette A. Krause, Mu-Jeng Cheng, Wei Liu

{"title":"Synthesis of chiral difluoromethyl cyclopropanes through desymmetric difluoromethylation of cyclopropenes enabled by enantioselective copper catalysis","authors":"Decai Ding, Su Chen, Lingfeng Yin, Wei-Ting Ou, Jeanette A. Krause, Mu-Jeng Cheng, Wei Liu","doi":"10.1038/s44160-025-00809-4","DOIUrl":"10.1038/s44160-025-00809-4","url":null,"abstract":"The incorporation of enantioenriched difluoromethyl cyclopropane (DFC) groups into drug candidates has garnered increasing attention in the pharmaceutical industry due to the unique ability of the DFC groups to serve as conformationally rigid hydrogen-bond donors. Despite their potential, the widespread use of chiral DFC groups has been limited by their challenging synthesis. Here we report the use of difluoromethyl–copper complexes for the development of a desymmetric difluoromethylation reaction, using enantioselective copper catalysis. Through desymmetric difluoromethylation of cyclopropenes and subsequent electrophilic functionalization, this method achieves high efficiency and enantioselectivity, enabling the modular construction of chiral DFC moieties. The synthetic utility of this strategy is demonstrated through the synthesis of a variety of chiral DFC-containing compounds, including analogues of pharmacologically relevant molecules. This reactivity of difluoromethyl–copper species opens opportunities for broader application in medicinal chemistry and the development of reactions for the construction of difluoromethyl-containing stereocentres. General methods for the synthesis of chiral difluoromethyl cyclopropanes are challenging to develop, despite the increasing importance of this motif in pharmaceuticals. Now, a copper-catalysed desymmetric difluoromethylation method is reported for the modular synthesis of difluoromethyl cyclopropanes with high efficiency and enantioselectivity.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"4 9","pages":"1118-1127"},"PeriodicalIF":20.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of fully π-conjugated non-alternant carbon nanobelts 全π共轭非交替碳纳米带的合成

IF 2

Nature synthesis Pub Date : 2025-05-16 DOI: 10.1038/s44160-025-00797-5

Yi Han, Shaofei Wu, Koon Yong Shawn Khoo, Chunyan Chi

{"title":"Synthesis of fully π-conjugated non-alternant carbon nanobelts","authors":"Yi Han, Shaofei Wu, Koon Yong Shawn Khoo, Chunyan Chi","doi":"10.1038/s44160-025-00797-5","DOIUrl":"10.1038/s44160-025-00797-5","url":null,"abstract":"Synthesizing carbon nanobelts (CNBs) with more delocalized electronic structures and enhanced π-conjugation remains challenging yet fundamentally important. Here we address this challenge and present the synthesis and characterization of fully π-conjugated, pentagon-embedded non-alternant CNBs. The nanobelts are meticulously designed with optimal strain and reactive site protection. The compounds are synthesized using an iterative Diels–Alder reaction followed by deoxygenative aromatization. Compared with all-benzenoid alternant CNBs, these CNBs exhibit smaller band gaps, stronger red emission and more effective π-conjugation owing to the incorporation of non-alternant moieties. Notably, one of the CNBs can be oxidized into its dication with an open-shell singlet ground state. Additionally, theoretical calculations indicate that the dication exhibits global aromaticity, characterized by two weakly coupled [32]annulenes with Baird-type aromaticity along its edges. This work opens avenues for synthesizing complex carbon nanostructures with enhanced electronic properties. The synthesis of fully π-conjugated, pentagon-embedded non-alternant carbon nanobelts is realized using an iterative Diels–Alder reaction followed by deoxygenative aromatization. Compared with all-benzenoid alternant counterparts, these carbon nanobelts have smaller band gaps, stronger red emission and more effective π-conjugation.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"4 8","pages":"947-955"},"PeriodicalIF":20.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Embedding pentagonal rings to access fully π-conjugated carbon nanobelts 嵌入五边形环以获得全π共轭碳纳米带

IF 2

Nature synthesis Pub Date : 2025-05-16 DOI: 10.1038/s44160-025-00807-6

引用次数: 0

A molecular sieve boosts perovskite stability 分子筛可以提高钙钛矿的稳定性

IF 2

Nature synthesis Pub Date : 2025-05-16 DOI: 10.1038/s44160-025-00808-5

Giulia Grancini, Carolin M. Sutter-Fella

引用次数: 0

The synthesis of energy materials 能源材料的合成

IF 2

Nature synthesis Pub Date : 2025-05-14 DOI: 10.1038/s44160-025-00814-7

引用次数: 0

Enantioselective type II intramolecular [5 + 2] cycloadditions of oxidopyrylium ylides using chiral-phosphoric-acid catalysis 手性磷酸催化氧化yryylides分子内[5 + 2]环加成的对映选择性II型

IF 2

Nature synthesis Pub Date : 2025-05-12 DOI: 10.1038/s44160-025-00803-w

Liangliang Yang, Ka Lok Chan, Ka Key Cheung, Pauline Chiu, Zhenyang Lin, Jianwei Sun

{"title":"Enantioselective type II intramolecular [5 + 2] cycloadditions of oxidopyrylium ylides using chiral-phosphoric-acid catalysis","authors":"Liangliang Yang, Ka Lok Chan, Ka Key Cheung, Pauline Chiu, Zhenyang Lin, Jianwei Sun","doi":"10.1038/s44160-025-00803-w","DOIUrl":"10.1038/s44160-025-00803-w","url":null,"abstract":"Intramolecular [5 + 2] cycloaddition reactions of oxidopyrylium ylides provide rapid access to privileged bridged seven-membered polycyclic structures. In particular, type II variants provide convenient access to highly strained adducts bearing an anti-Bredt double bond. However, enantioselective variants using catalytic methods remain unknown. Here we report an enantioselective method enabled by a non-covalent activation strategy using chiral acid catalysis. The use of a suitable leaving group in the oxidopyrylium precursor and an effective chiral-phosphoric-acid catalyst are crucial to the process. Multiple stereogenic centres can be constructed in one step with high efficiency and excellent enantioselectivity and diastereoselectivity under mild conditions. The products generated from this process are not only structurally intriguing but also represent core structures or advanced intermediates found in natural products. Both mechanistic experiments and computational calculations reveal that enolization is the rate-determining step, whereas the cycloaddition is the enantiodetermining step. Intramolecular [5 + 2] cycloaddition reactions of oxidopyrylium ylides provide access to privileged bridged seven-membered polycyclic structures. Now, an enantioselective method enabled by a non-covalent activation strategy using chiral acid catalysis is reported, allowing multiple stereogenic centres to be constructed in one step with high efficiency, enantioselectivity and diastereoselectivity.","PeriodicalId":74251,"journal":{"name":"Nature synthesis","volume":"4 10","pages":"1223-1231"},"PeriodicalIF":20.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0