Pub Date : 2025-10-22DOI: 10.1016/j.tet.2025.135020
Jiajin Wu , Wenxue Wang , Xinsheng Huang , Luning Zhou , Yi He , Yuting Liu , Guojian Zhang , Qian Che , Jing Li , Tianjiao Zhu , Dehai Li
Three new terpenoids (1, 3, and 8), including one new cyclohexenoneterpene analogue talaroterpene A (1), one new meroterpenoid chrodrimanin U (3), one new preaustinoid-related meroterpenoid preaustinoid A8 (8), together with one new natural preaustinoid-related meroterpenoid (9), and six known meroterpenoids (2, 4–7, and 10) were isolated from the deep-sea cold seep derived fungus Talaromyces amestolkiae HDN21-0307 using NaBr-supplemented one strain many compounds (OSMAC) approach. Compound 3 represents the first meroterpenoid compound with a benzene ring as its E-ring. Their structures were elucidated by spectroscopic data analysis and quantum chemical calculations. Bioactivity tests revealed that compound 8 exhibited antibacterial activity against Staphylococcus aureus with an MIC value of 8.0 μg/mL. Compounds 3 and 8 showed significant cytotoxic activity against NCI–H446/EP cells with IC50 values of 6.9 and 8.2 μM, respectively.
{"title":"Discovery of new cytotoxic terpenoids from Talaromyces amestolkiae HDN21-0307 through NaBr-supplemented OSMAC strategy","authors":"Jiajin Wu , Wenxue Wang , Xinsheng Huang , Luning Zhou , Yi He , Yuting Liu , Guojian Zhang , Qian Che , Jing Li , Tianjiao Zhu , Dehai Li","doi":"10.1016/j.tet.2025.135020","DOIUrl":"10.1016/j.tet.2025.135020","url":null,"abstract":"<div><div>Three new terpenoids (<strong>1, 3,</strong> and <strong>8</strong>), including one new cyclohexenoneterpene analogue talaroterpene A (<strong>1</strong>), one new meroterpenoid chrodrimanin U (<strong>3</strong>), one new preaustinoid-related meroterpenoid preaustinoid A8 (<strong>8</strong>), together with one new natural preaustinoid-related meroterpenoid (<strong>9</strong>), and six known meroterpenoids (<strong>2, 4</strong>–<strong>7,</strong> and <strong>10</strong>) were isolated from the deep-sea cold seep derived fungus <em>Talaromyces amestolkiae</em> HDN21-0307 using NaBr-supplemented one strain many compounds (OSMAC) approach. Compound <strong>3</strong> represents the first meroterpenoid compound with a benzene ring as its E-ring. Their structures were elucidated by spectroscopic data analysis and quantum chemical calculations. Bioactivity tests revealed that compound <strong>8</strong> exhibited antibacterial activity against <em>Staphylococcus aureus</em> with an MIC value of 8.0 μg/mL. Compounds <strong>3</strong> and <strong>8</strong> showed significant cytotoxic activity against NCI–H446/EP cells with IC<sub>50</sub> values of 6.9 and 8.2 μM, respectively.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"189 ","pages":"Article 135020"},"PeriodicalIF":2.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-22DOI: 10.1016/j.tet.2025.135007
Zhaolong Ma , Yuhang Zhao , Yudi Xu , Xuqin Li
A direct ortho-C-H sulfonamidation of N-aryl phthalazinones has been developed via a Rh(III)-catalyzed C–N coupling with sulfonyl azides. The reaction proceeds under mild oxidative conditions using [RhCp*Cl2]2 (4 mol%) as the catalyst, AgSbF6 (16 mol%) as the additive, KOAc (2.0 equiv) as the base, in THF at 120 °C under air for 24 h. This method provides a concise and regioselective approach to access a broad range of sulfonamidated phthalazinone derivatives, with good functional group tolerance. Furthermore, the reaction has been demonstrated on a preparative scale, highlighting its synthetic applicability.
{"title":"Rh(III)-catalyzed C–H sulfonamidation of N-aryl phthalazinones using benzenesulfonyl azides","authors":"Zhaolong Ma , Yuhang Zhao , Yudi Xu , Xuqin Li","doi":"10.1016/j.tet.2025.135007","DOIUrl":"10.1016/j.tet.2025.135007","url":null,"abstract":"<div><div>A direct ortho-C-H sulfonamidation of N-aryl phthalazinones has been developed via a Rh(III)-catalyzed C–N coupling with sulfonyl azides. The reaction proceeds under mild oxidative conditions using [RhCp*Cl<sub>2</sub>]<sub>2</sub> (4 mol%) as the catalyst, AgSbF<sub>6</sub> (16 mol%) as the additive, KOAc (2.0 equiv) as the base, in THF at 120 °C under air for 24 h. This method provides a concise and regioselective approach to access a broad range of sulfonamidated phthalazinone derivatives, with good functional group tolerance. Furthermore, the reaction has been demonstrated on a preparative scale, highlighting its synthetic applicability.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"189 ","pages":"Article 135007"},"PeriodicalIF":2.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-22DOI: 10.1016/j.tet.2025.135022
Dongxian Geng , Lu Jin , Qinxiang Jia , Xiaoyong Li , Yong Wu , Yang Sun
Baeyer–Villiger oxidation is an efficient method of synthesizing value-added esters or lactones by inserting of an oxygen atom into ketones. Inexpensive bimetallic MIL-100(Fe,Cu) catalysts are prepared with a green and mild experimental technique. The catalysts have been comprehensively characterized and tested their catalytic performance of aerobic Baeyer–Villiger oxidation. Screening experiments are conducted to evaluate the effects of reaction time, temperature, the molar ratio of benzaldehyde to cyclohexanone, and catalyst mass on the oxidation of cyclohexanone. Surprisingly, it is observed that a catalyst in a ratio of 6:1 (Fe to Cu) exhibits high catalytic activity (99 % cyclohexanone conversion and 99 % ε-caprolactone yield). The scope of substrates indicates that the screened catalyst demonstrates moderate to high activity for five- and six-membered cyclic ketones. Furthermore, the prepared catalyst is thermally stable and exhibits significant recycling activity (>96 %). The reaction mechanism and the role of the catalyst are clarified through computational study. The catalyst can first trap and activate O2 to oxidize benzaldehyde towards benzoyl peroxy acid. Significantly, the high catalytic activity would be attributed to the copper-modulated morphology of the catalyst. The activation energy is estimated to be 19 kcal/mol in the kinetic experiments. Consequently, we have developed an inexpensive MIL-100(Fe,Cu) catalyst via a green synthetic method for an aerobic Baeyer-Villiger oxidation of cyclic ketones to lactones.
{"title":"Green synthesis of bimetallic MIL-100(Fe,Cu) MOFs and their catalytic application in an aerobic Baeyer–Villiger oxidation of cyclic ketones","authors":"Dongxian Geng , Lu Jin , Qinxiang Jia , Xiaoyong Li , Yong Wu , Yang Sun","doi":"10.1016/j.tet.2025.135022","DOIUrl":"10.1016/j.tet.2025.135022","url":null,"abstract":"<div><div>Baeyer–Villiger oxidation is an efficient method of synthesizing value-added esters or lactones by inserting of an oxygen atom into ketones. Inexpensive bimetallic MIL-100(Fe,Cu) catalysts are prepared with a green and mild experimental technique. The catalysts have been comprehensively characterized and tested their catalytic performance of aerobic Baeyer–Villiger oxidation. Screening experiments are conducted to evaluate the effects of reaction time, temperature, the molar ratio of benzaldehyde to cyclohexanone, and catalyst mass on the oxidation of cyclohexanone. Surprisingly, it is observed that a catalyst in a ratio of 6:1 (Fe to Cu) exhibits high catalytic activity (99 % cyclohexanone conversion and 99 % ε-caprolactone yield). The scope of substrates indicates that the screened catalyst demonstrates moderate to high activity for five- and six-membered cyclic ketones. Furthermore, the prepared catalyst is thermally stable and exhibits significant recycling activity (>96 %). The reaction mechanism and the role of the catalyst are clarified through computational study. The catalyst can first trap and activate O<sub>2</sub> to oxidize benzaldehyde towards benzoyl peroxy acid. Significantly, the high catalytic activity would be attributed to the copper-modulated morphology of the catalyst. The activation energy is estimated to be 19 kcal/mol in the kinetic experiments. Consequently, we have developed an inexpensive MIL-100(Fe,Cu) catalyst via a green synthetic method for an aerobic Baeyer-Villiger oxidation of cyclic ketones to lactones.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"190 ","pages":"Article 135022"},"PeriodicalIF":2.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145384504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Phosphotriesters play a crucial role in pharmaceutical development, acting as key intermediates and prodrug components that enhance membrane permeability and enzymatic stability. Here, we develop two oxidative phosphorylation methods utilizing 1,4-dihydropyridine-N-phosphoramides as phosphoryl donors. The first method employs a photoredox catalyst and a stoichiometric weak oxidant, achieving efficient phosphotriester synthesis under mild conditions. The second method uses a hybrid catalytic system that incorporates a photoredox catalyst, a hydrogen atom transfer (HAT) catalyst, and a cobaloxime catalyst, allowing for dehydrogenative phosphorylation without the need for external oxidants or bases. This ternary catalytic approach improves reaction efficiency, and might offer a potential alternative to existing methodologies. Mechanistic investigations, including control experiments and DFT calculations, confirm the role of oxidative activation in facilitating nucleophilic substitution. This study presents a novel approach to the mild and selective synthesis of phosphotriesters, with potential applications in drug discovery and organic synthesis.
磷酸三酯在药物开发中起着至关重要的作用，是增强膜通透性和酶稳定性的关键中间体和前药成分。在这里，我们开发了两种氧化磷酸化方法，利用1,4-二氢吡啶- n -磷酰胺作为磷酸化给体。第一种方法采用光氧化还原催化剂和化学计量弱氧化剂，在温和条件下实现了磷酸三酯的高效合成。第二种方法使用混合催化系统，该系统包含光氧化还原催化剂、氢原子转移（HAT）催化剂和钴胺肟催化剂，允许脱氢磷酸化，而不需要外部氧化剂或碱。这种三元催化方法提高了反应效率，并可能提供现有方法的潜在替代方案。机理研究，包括对照实验和DFT计算，证实了氧化活化在促进亲核取代中的作用。本研究提出了一种温和选择性合成磷酸三酯的新方法，在药物发现和有机合成方面具有潜在的应用前景。
{"title":"Photocatalytic phosphorylation of alcohols via oxidative activation of 1,4-dihydropyridine-N-phosphoramide","authors":"Kohei Fujiyoshi, Suguru Arii, Kenzo Yamatsugu, Harunobu Mitsunuma, Motomu Kanai","doi":"10.1016/j.tet.2025.135008","DOIUrl":"10.1016/j.tet.2025.135008","url":null,"abstract":"<div><div>Phosphotriesters play a crucial role in pharmaceutical development, acting as key intermediates and prodrug components that enhance membrane permeability and enzymatic stability. Here, we develop two oxidative phosphorylation methods utilizing 1,4-dihydropyridine-<em>N</em>-phosphoramides as phosphoryl donors. The first method employs a photoredox catalyst and a stoichiometric weak oxidant, achieving efficient phosphotriester synthesis under mild conditions. The second method uses a hybrid catalytic system that incorporates a photoredox catalyst, a hydrogen atom transfer (HAT) catalyst, and a cobaloxime catalyst, allowing for dehydrogenative phosphorylation without the need for external oxidants or bases. This ternary catalytic approach improves reaction efficiency, and might offer a potential alternative to existing methodologies. Mechanistic investigations, including control experiments and DFT calculations, confirm the role of oxidative activation in facilitating nucleophilic substitution. This study presents a novel approach to the mild and selective synthesis of phosphotriesters, with potential applications in drug discovery and organic synthesis.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"189 ","pages":"Article 135008"},"PeriodicalIF":2.2,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-21DOI: 10.1016/j.tet.2025.135019
Jing Zhou, Man Jiang, Yu Luo, Hai-Lei Cui
We have established a chemoselective synthesis of indolizino [8,7-b]indoles with pyrrole-tethered indoles through electrophilic dearomative cyclization in the presence of organic bromide/sulfoxide. A series of 7,9-dibromo-6,11-dihydro-5H-indolizino [8,7-b]indoles can be assembled in AcBr/TMSO (tetramethylene sulfoxide)/DCM, while mono-brominated indolizino [8,7-b]indoles could be prepared as major products by switching to DMF as solvent. In addition, 6,11-dihydro-5H-indolizino [8,7-b]indole derivatives were obtained selectively by treating pyrrole-tethered indoles with methyl bromoacetate/DMSO. Easily accessible organic bromides and sulfoxide serve as the bromine source and oxidant respectively.
{"title":"Bromide/sulfoxide-promoted dearomative construction of indolizino[8,7-b]indoles","authors":"Jing Zhou, Man Jiang, Yu Luo, Hai-Lei Cui","doi":"10.1016/j.tet.2025.135019","DOIUrl":"10.1016/j.tet.2025.135019","url":null,"abstract":"<div><div>We have established a chemoselective synthesis of indolizino [8,7-<em>b</em>]indoles with pyrrole-tethered indoles through electrophilic dearomative cyclization in the presence of organic bromide/sulfoxide. A series of 7,9-dibromo-6,11-dihydro-5<em>H</em>-indolizino [8,7-<em>b</em>]indoles can be assembled in AcBr/TMSO (tetramethylene sulfoxide)/DCM, while mono-brominated indolizino [8,7-<em>b</em>]indoles could be prepared as major products by switching to DMF as solvent. In addition, 6,11-dihydro-5<em>H</em>-indolizino [8,7-<em>b</em>]indole derivatives were obtained selectively by treating pyrrole-tethered indoles with methyl bromoacetate/DMSO. Easily accessible organic bromides and sulfoxide serve as the bromine source and oxidant respectively.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"189 ","pages":"Article 135019"},"PeriodicalIF":2.2,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-18DOI: 10.1016/j.tet.2025.135002
Zhen-Jiang Qiu , Xian-Hui Huang , Ruo-Ling Jia , Guo-Yi Yan , Ran Xia , Yong-Bo Yu , Peng Liu , Shu-Zhan Zhang , Wu-Bin Zhi , Shao-Hong Xu
Tandem reductive amination is a fundamental reaction in organic chemistry. The synthesis of secondary amines, notably the one-pot synthesis of low-cost aldehydes and nitro compounds using tandem processes including nitro reduction, imine creation, and imine reduction, has sparked great interest. The present work describes a mild synthesis of N-benzylanilines that does not need metal catalysts or high-pressure hydrogen. The method uses a wide variety of substrates and generates water as an environmentally friendly byproduct.
{"title":"Construction of N-benzylanilines via facile metal-free tandem reductive amination of benzaldehydes with nitrobenzenes","authors":"Zhen-Jiang Qiu , Xian-Hui Huang , Ruo-Ling Jia , Guo-Yi Yan , Ran Xia , Yong-Bo Yu , Peng Liu , Shu-Zhan Zhang , Wu-Bin Zhi , Shao-Hong Xu","doi":"10.1016/j.tet.2025.135002","DOIUrl":"10.1016/j.tet.2025.135002","url":null,"abstract":"<div><div>Tandem reductive amination is a fundamental reaction in organic chemistry. The synthesis of secondary amines, notably the one-pot synthesis of low-cost aldehydes and nitro compounds using tandem processes including nitro reduction, imine creation, and imine reduction, has sparked great interest. The present work describes a mild synthesis of N-benzylanilines that does not need metal catalysts or high-pressure hydrogen. The method uses a wide variety of substrates and generates water as an environmentally friendly byproduct.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"189 ","pages":"Article 135002"},"PeriodicalIF":2.2,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-18DOI: 10.1016/j.tet.2025.135000
Junyang Tang , Yaorong Liu , Baojie Qiu , Chun He , Xingxian Zhang
A palladium-catalyzed arene ortho C–H chlorination of 4-aryl-pyrrolo[2,3-d]pyrimidines has been developed using inexpensive p-toluenesulfonyl chloride (TsCl) as a practical chlorine source. This transformation endows facile fabrication of C–Cl bond with high regioselectivity and wide functional group tolerance exploiting directing properties of pyrimidinic nitrogen on pharmacodynamic 7-deazapurines. The synthetic utility of this protocol is demonstrated through gram-scale synthesis and diverse late-stage functionalization.
{"title":"Pd-catalyzed site-selective arene ortho C–H chlorination of 4-aryl-pyrrolo[2,3-d]pyrimidines with para- toluenesulfonylchloride","authors":"Junyang Tang , Yaorong Liu , Baojie Qiu , Chun He , Xingxian Zhang","doi":"10.1016/j.tet.2025.135000","DOIUrl":"10.1016/j.tet.2025.135000","url":null,"abstract":"<div><div>A palladium-catalyzed arene <em>ortho</em> C–H chlorination of 4-aryl-pyrrolo[2,3-<em>d</em>]pyrimidines has been developed using inexpensive <em>p</em>-toluenesulfonyl chloride (TsCl) as a practical chlorine source. This transformation endows facile fabrication of C–Cl bond with high regioselectivity and wide functional group tolerance exploiting directing properties of pyrimidinic nitrogen on pharmacodynamic 7-deazapurines. The synthetic utility of this protocol is demonstrated through gram-scale synthesis and diverse late-stage functionalization.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"190 ","pages":"Article 135000"},"PeriodicalIF":2.2,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A new pyrrolidine alkaloid, tamaractam, was isolated from a traditional herbal medicine that is historically used for the treatment of rheumatoid arthritis (RA). Herein, we describe a synthetic method for the production of tamaractam through a novel cascade radical 1,4-aryl migration and an aldol-type condensation. Started from inexpensive starting material, vanillin, the key precursor could be prepared from the coupling reaction of a corresponding aryl acid and propargyl amine, followed by Boc-protection. Under a metal-free cascade radical 1,4-aryl migration, an advanced β-aryl-γ-lactam was produced and further confirmed by an X-ray crystal structure. The aldol reaction between the β-aryl-γ-lactam and the second equivalent of the vanillin derivative was proceeded, followed by one-pot dehydration and deprotection under acidic conditions to produce tamaractam for the first time. This procedure also provides a general and concise synthetic method for the synthesis of exocyclic α,α′-unsaturated-β-aryl-γ-lactam types of natural products.
{"title":"First total synthesis of tamaractam through cascade radical 1,4-aryl migration","authors":"Yu-Tong Huang , Chia-Lin Li , Chuan-Jing Lin, Yi-Xuan Chan, Che-Chien Chang","doi":"10.1016/j.tet.2025.135006","DOIUrl":"10.1016/j.tet.2025.135006","url":null,"abstract":"<div><div>A new pyrrolidine alkaloid, tamaractam, was isolated from a traditional herbal medicine that is historically used for the treatment of rheumatoid arthritis (RA). Herein, we describe a synthetic method for the production of tamaractam through a novel cascade radical 1,4-aryl migration and an aldol-type condensation. Started from inexpensive starting material, vanillin, the key precursor could be prepared from the coupling reaction of a corresponding aryl acid and propargyl amine, followed by Boc-protection. Under a metal-free cascade radical 1,4-aryl migration, an advanced β-aryl-γ-lactam was produced and further confirmed by an X-ray crystal structure. The aldol reaction between the β-aryl-γ-lactam and the second equivalent of the vanillin derivative was proceeded, followed by one-pot dehydration and deprotection under acidic conditions to produce tamaractam for the first time. This procedure also provides a general and concise synthetic method for the synthesis of exocyclic α,α′-unsaturated-β-aryl-γ-lactam types of natural products.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"189 ","pages":"Article 135006"},"PeriodicalIF":2.2,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-17DOI: 10.1016/j.tet.2025.135001
Kun Liu, Kexin Wang, Xiyan Duan, Panjie Wang, Xinsheng Wang, Zhiwei Han, Zishan Fu, Xingyi Sun, Hanglian Wu, Jiayu Gao, Pu Liu
ARB-272572 is a potent small molecule inhibitor of programmed cell death ligand 1 (PD-L1) currently in preclinical trials for the treatment of colorectal cancer, which is the second leading cause of cancer-related deaths worldwide. Herein, we report a new synthetic route of ARB-272572 starting from methyl 5-(hydroxymethyl)picolinate via five steps: bromination, amination, hydrolysis and amination protection, condensation, and deprotection. This new synthetic route avoids the use of toxic chemicals and achieves a significant increase in yield compared to existing synthetic routes.
{"title":"A new synthetic route for the preparation of programmed cell death ligand 1 inhibitor: ARB-272572","authors":"Kun Liu, Kexin Wang, Xiyan Duan, Panjie Wang, Xinsheng Wang, Zhiwei Han, Zishan Fu, Xingyi Sun, Hanglian Wu, Jiayu Gao, Pu Liu","doi":"10.1016/j.tet.2025.135001","DOIUrl":"10.1016/j.tet.2025.135001","url":null,"abstract":"<div><div>ARB-272572 is a potent small molecule inhibitor of programmed cell death ligand 1 (PD-L1) currently in preclinical trials for the treatment of colorectal cancer, which is the second leading cause of cancer-related deaths worldwide. Herein, we report a new synthetic route of ARB-272572 starting from methyl 5-(hydroxymethyl)picolinate via five steps: bromination, amination, hydrolysis and amination protection, condensation, and deprotection. This new synthetic route avoids the use of toxic chemicals and achieves a significant increase in yield compared to existing synthetic routes.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"189 ","pages":"Article 135001"},"PeriodicalIF":2.2,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145327264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A cyanuric chloride (TCT)-promoted approach was developed for synthesizing N-sulfonyl (form)amidines via direct condensation of sulfonamides and (form)amides under mild conditions. This method accommodates a broad range of aliphatic and (hetero)aromatic sulfonamides containing electron-donating or electron-withdrawing groups, as well as various acyclic and cyclic (form)amides, which were efficiently converted into the corresponding N-sulfonyl(form)amidines in good to excellent yields. Notably, the methodology is scalable to gram quantities and applicable to the late-stage derivatization of bioactive sulfonamides, offering a versatile strategy for constructing biologically relevant molecules.
{"title":"TCT promoted efficient synthesis of N-sulfonyl (form)amidines from sulfonamides and (form)amides","authors":"Maierhaba Julaiti , Pinchang Sun , Bumairemu Aizezi , Abudureheman Wusiman","doi":"10.1016/j.tet.2025.135005","DOIUrl":"10.1016/j.tet.2025.135005","url":null,"abstract":"<div><div>A cyanuric chloride (TCT)-promoted approach was developed for synthesizing <em>N</em>-sulfonyl (form)amidines via direct condensation of sulfonamides and (form)amides under mild conditions. This method accommodates a broad range of aliphatic and (hetero)aromatic sulfonamides containing electron-donating or electron-withdrawing groups, as well as various acyclic and cyclic (form)amides, which were efficiently converted into the corresponding <em>N</em>-sulfonyl(form)amidines in good to excellent yields. Notably, the methodology is scalable to gram quantities and applicable to the late-stage derivatization of bioactive sulfonamides, offering a versatile strategy for constructing biologically relevant molecules.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"189 ","pages":"Article 135005"},"PeriodicalIF":2.2,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145326943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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