Tetrahedron chem最新文献

1,2,5-Thiadiazocan-7-one 1,1-dioxides — a novel charted region in the chemical space of 8-membered azasultams 1,2,5-噻二唑烷-7- 1- 1,1-二氧化物- 8元氮杂化合物化学空间中的新区域

Tetrahedron chem Pub Date : 2026-03-01 Epub Date: 2026-02-21 DOI: 10.1016/j.tchem.2026.100156

Olena D. Semoshkina , Demyd S. Milokhov , Vasyl Y. Hys , Magdalina D. Tsapko , Andrii V. Yatsymyrskyi , Anton O. Poliudov , Svitlana V. Shishkina , Alexey V. Dobrydnev , Yulian M. Volovenko

{"title":"1,2,5-Thiadiazocan-7-one 1,1-dioxides — a novel charted region in the chemical space of 8-membered azasultams","authors":"Olena D. Semoshkina , Demyd S. Milokhov , Vasyl Y. Hys , Magdalina D. Tsapko , Andrii V. Yatsymyrskyi , Anton O. Poliudov , Svitlana V. Shishkina , Alexey V. Dobrydnev , Yulian M. Volovenko","doi":"10.1016/j.tchem.2026.100156","DOIUrl":"10.1016/j.tchem.2026.100156","url":null,"abstract":"<div><div>Herein, we describe an efficient and cost-effective synthesis of previously unreported 1,2,5-thiadiazocan-7-one 1,1-dioxides through the CSIC (Carbanion-mediated Sulfonate (Sulfonamide) Intermolecular Coupling (Intramolecular Cyclization) reaction strategy. These compounds belong to a small family of 8-membered cyclic sulfonamides, possessing an additional endocyclic nitrogen atom and therefore abbreviated as <em>aza</em>sultams (a portmanteau of aza + sulfa lactam). The target <em>aza</em>sultams were prepared in a few simple steps and in good overall yield from readily available reagents. Particularly, the alkylation of <em>NH</em>-heteroaryl carboxylates with <em>N</em>,<em>O</em>-dimesylated β-aminoalcohols gave the corresponding 1-(2-(<em>N</em>-methylsulfonamido)ethyl)-1<em>H</em>-heteroaroyl-2-carboxylates, which underwent base-mediated <em>sulfa</em>-Dieckmann condensation affording the target 8-membered <em>aza</em>sultams. To demonstrate the synthetic utility of 1,2,5-thiadiazocan-7-one 1,1-dioxides, a few derivatizations were attempted, thereby expanding the limited chemical space of the relatively underrepresented 8-membered <em>aza</em>sultams. The combined NMR and X-ray diffraction study, supported by DFT calculations, allowed us to investigate the structural features of functionalized 1,2,5-thiadiazocane 1,1-dioxides, formulate the structure-activity relationship, and estimate the strain energy. Finally, the molecular docking study predicted a strong binding affinity of the selected <em>aza</em>sultams to cancer-associated receptors, which are therapeutic targets in cancer treatment.</div></div>","PeriodicalId":74918,"journal":{"name":"Tetrahedron chem","volume":"17 ","pages":"Article 100156"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147398305","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

Stepwise dual N-terminal modification of proteins via nickel(II)-mediated aldol and Pictet–Spengler reactions 通过镍（II）介导的aldol和Pictet-Spengler反应逐步对蛋白质进行双n端修饰

Tetrahedron chem Pub Date : 2026-03-01 Epub Date: 2026-01-29 DOI: 10.1016/j.tchem.2026.100154

Kengo Hanaya , Yuki Morimi , Shoma Usui , Kazuaki Taguchi , Yuki Wada , Masaki Kawano , Shuhei Higashibayashi , Takeshi Sugai

{"title":"Stepwise dual N-terminal modification of proteins via nickel(II)-mediated aldol and Pictet–Spengler reactions","authors":"Kengo Hanaya , Yuki Morimi , Shoma Usui , Kazuaki Taguchi , Yuki Wada , Masaki Kawano , Shuhei Higashibayashi , Takeshi Sugai","doi":"10.1016/j.tchem.2026.100154","DOIUrl":"10.1016/j.tchem.2026.100154","url":null,"abstract":"<div><div>The dual modification of proteins with two distinct artificial functionalities significantly broadens the scope and utility of protein conjugates. To achieve this, it is necessary to perform site-specific and stoichiometrically controlled modifications, for which the N-terminus is a promising target owing to its unique accessibility and chemical reactivity. In this study, a sequential N-terminal dual-modification strategy was developed that combines a nickel(II)-mediated aldol reaction (using imidazo[1,2-a]pyridine-2-carbaldehyde derivatives) with a subsequent Pictet–Spengler reaction (using 2-pyridinecarboxaldehyde derivatives) at the N-terminus. Both transformations employ structurally simple, readily accessible reagents and proceed under mild, non-denaturing aqueous conditions (pH 7 and 5.5, 37 °C). Using this approach, the dual modification of myoglobin and trastuzumab was achieved. The resulting trastuzumab conjugate, bearing Cy5 (a fluorescent dye) and monomethyl auristatin E (a potent cytotoxic agent), retained the ability to recognize human epidermal growth factor receptor 2 (HER2) and exhibited potent cytotoxicity against HER2-positive cancer cell lines. This sequential method established the N-terminus as a versatile alternative to cysteine for dual functionalization, enabling the creation of well-defined multifunctional protein conjugates using simple, modular chemistry.</div></div>","PeriodicalId":74918,"journal":{"name":"Tetrahedron chem","volume":"17 ","pages":"Article 100154"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079379","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

Structural optimization of 3,4-dihydroquinolizinium ring toward practical application for chemo-selective modification of cysteine 面向半胱氨酸化学选择性修饰的3,4-二氢喹啉环结构优化

Tetrahedron chem Pub Date : 2026-03-01 Epub Date: 2026-02-14 DOI: 10.1016/j.tchem.2026.100155

Wataru Kondo , Kazuhiro Irie , Yu Nakagawa

{"title":"Structural optimization of 3,4-dihydroquinolizinium ring toward practical application for chemo-selective modification of cysteine","authors":"Wataru Kondo , Kazuhiro Irie , Yu Nakagawa","doi":"10.1016/j.tchem.2026.100155","DOIUrl":"10.1016/j.tchem.2026.100155","url":null,"abstract":"<div><div>3,4-Dihydroquinolizinium (DQ) ring, a core structure of naturally-occurring quinocidin, reacts with cysteine (Cys) through Michael addition-type reaction in neutral aqueous media. In this study, we performed structural optimization of the DQ ring toward practical application for chemo-selective modification of Cys. Stability evaluation of the DQ–Cys adduct revealed that the adduct was gradually decomposed in neutral buffered solutions to regenerate the DQ ring through retro-Michael reaction. This observation led us to design 9-methoxy and 9-ethoxy DQ rings, which rapidly and selectively reacted with Cys and the resulting adducts showed higher stability compared with the non-substituted DQ–Cys adduct. We also demonstrated that the 9-ethoxy DQ ring is superior to the non-substituted one in regard to the reactivity toward Cys residues in peptides and the inhibitory activity against glyceraldehyde-3-phosphate dehydrogenase containing a Cys residue in its active center. These results indicate that the 9-alkoxy DQ rings could serve as practical Cys-selective electrophiles, which expand the toolbox of the methodologies available for Cys modification in biological and pharmacological research.</div></div>","PeriodicalId":74918,"journal":{"name":"Tetrahedron chem","volume":"17 ","pages":"Article 100155"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147398276","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

Recent advances in the late-stage modification of complex bioactive molecules with oxetanes and azetidines 复合生物活性分子与氧烷和氮杂啶的后期修饰研究进展

Tetrahedron chem Pub Date : 2026-03-01 Epub Date: 2026-01-09 DOI: 10.1016/j.tchem.2026.100153

Yuqing Wang, Dayu Tian, Hai-Jun Zhang

引用次数: 0

Electrochemically driven strategies: Recent developments in chalcogenation (S/Se/Te) of organic molecules 电化学驱动策略：有机分子硫化（S/Se/Te）的最新进展

Tetrahedron chem Pub Date : 2025-12-01 Epub Date: 2025-11-26 DOI: 10.1016/j.tchem.2025.100149

Anil Balajirao Dapkekar , Naveen Jakkula , Pradip S. Waghmare, Satyanarayana Gedu

{"title":"Electrochemically driven strategies: Recent developments in chalcogenation (S/Se/Te) of organic molecules","authors":"Anil Balajirao Dapkekar , Naveen Jakkula , Pradip S. Waghmare, Satyanarayana Gedu","doi":"10.1016/j.tchem.2025.100149","DOIUrl":"10.1016/j.tchem.2025.100149","url":null,"abstract":"<div><div>Organochalcogen-containing (e.g., sulfur, selenium, and tellurium) molecules are indispensable in pharmaceuticals, natural products, agrochemicals, and materials science. Chalcogen-containing compounds exhibit unique activity, reactivity, and tunable properties, from the bioactive cores of pharmaceuticals to the functional backbones of catalysts and semiconductors. Yet, their synthesis has long relied on methods that often require stoichiometric oxidants, hazardous reagents, or transition metals, limiting sustainability and functional group tolerance. Electrochemical synthesis has emerged as a promising green alternative, utilizing electrons as traceless redox agents to facilitate the selective formation of C–X (X = S, Se, and Te) bonds under mild and sustainable conditions. In recent years, this approach has experienced remarkable growth, showcasing diverse strategies, including direct C–H functionalization, annulation/cascade cyclization, multicomponent reactions, and difunctionalization, with a broad substrate scope, exceptional selectivity, and compatibility for the late-stage functionalization of organic molecules. This review encompasses recent developments (March 2024–July 2025) in electrochemical chalcogenation, detailing reaction designs, mechanistic insights, and sustainability considerations, and outlines future opportunities for expanding the scope and industrial applicability of this electrochemical tool. We hope this review will serve as a base for future advancements in electrochemical chalcogenation strategies.</div></div>","PeriodicalId":74918,"journal":{"name":"Tetrahedron chem","volume":"16 ","pages":"Article 100149"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684506","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

Multifaceted reactivity of benzimidazoline as an electron donor, a hydride donor, and a catalyst 苯并咪唑啉作为电子给体、氢化物给体和催化剂的多方面反应性

Tetrahedron chem Pub Date : 2025-12-01 Epub Date: 2025-09-17 DOI: 10.1016/j.tchem.2025.100147

Tatsuhiro Harada, Suguru Murakami, Ryosuke Matsubara

引用次数: 0

Light-driven synthesis of 3-(hetero)aryl/alkyl-1-indanone derivatives from indan-1,3-diones and boronic acids via N-tosylhydrazones 以吲哚-1,3-二酮和硼酸为原料经n-甲苯腙催化合成3-（杂）芳基/烷基-1-吲哚酮衍生物

Tetrahedron chem Pub Date : 2025-12-01 Epub Date: 2025-12-02 DOI: 10.1016/j.tchem.2025.100150

Mohammad Junaid, Pokhriyal Yamini, Dongari Yadagiri

引用次数: 0

Synthesis of 4-styrylquinazolines enabled by a hypervalent iodine-promoted oxidative amination cascade 用高价碘促进氧化胺化级联反应合成4-苯基喹唑啉

Tetrahedron chem Pub Date : 2025-12-01 Epub Date: 2025-12-04 DOI: 10.1016/j.tchem.2025.100151

Lipeng Long , Ziyi Yu , Ziwen Huang , Min Ye , Wenjun Luo , Xunjin Jiang , Zhengwang Chen , Zhong-Xia Wang

引用次数: 0

A mechanistic perspective on the chemistry of biocatalytic desaturation 生物催化脱饱和的机理研究

Tetrahedron chem Pub Date : 2025-12-01 Epub Date: 2025-09-23 DOI: 10.1016/j.tchem.2025.100148

Yueyue Zhu , Weilin Wu , Shixuan Cao, Yuxuan Ye

引用次数: 0

Interview with the 2025 Tetrahedron young investigator award for organic synthesis 采访2025年有机合成四面体青年研究者奖

Tetrahedron chem Pub Date : 2025-09-01 Epub Date: 2025-06-13 DOI: 10.1016/j.tchem.2025.100140

Song Lin, Wing Ho So, Jun Kee Cheng

引用次数: 0