Tetrahedron Letters最新文献

{"title":"Biocatalytic synthesis of fluorine-containing chiral azido compounds in a two-phase system","authors":"Robert Junior Kolman ,&nbsp;Nevena Milčić ,&nbsp;Ivana Leščić Ašler ,&nbsp;Zoran Štefanić ,&nbsp;Petra Švaco ,&nbsp;Višnja Stepanić ,&nbsp;Zlatko Brkljača ,&nbsp;Irena Dokli ,&nbsp;Zvjezdana Findrik Blažević ,&nbsp;Maja Majerić Elenkov","doi":"10.1016/j.tetlet.2026.155982","DOIUrl":"10.1016/j.tetlet.2026.155982","url":null,"abstract":"<div><div>Halohydrin dehalogenases (HHDHs) offer a biocatalytic route to chiral azido alcohols and epoxides. In previous work, we reported an (<em>R</em>)-enantioselective azidolysis of fluorinated aromatic epoxides by HheC from <em>Agrobacterium radiobacter</em> AD1. Herein, we employed the HheA2-N178A variant, displaying high (<em>S</em>)-enantioselectivity, for the synthesis of a wide range of fluoroaromatic azido alcohols. Initially, we assayed 14 fluorinated styrene oxide derivatives and found high enantioselectivity in reactions (<em>E</em> up to 200), regardless of the substituent position. Biotransformations upscaled to 100 mM substrate concentration were carried out in a two-phase system, and the products were isolated in excellent enantiomeric purity (93 – &gt;99% <em>ee</em>). Additionally, the structure of HheA2-N178A enzyme was determined.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"178 ","pages":"Article 155982"},"PeriodicalIF":1.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of 1-thiazolyl-1H-indazoles from o-fluorobenzaldehyde thiazolylhydrazones","authors":"Thalita O. Daher ,&nbsp;Cristiane S. Schwalm ,&nbsp;Sidnei Moura ,&nbsp;Júlia Menin ,&nbsp;Bárbara Tirloni ,&nbsp;Gleison A. Casagrande ,&nbsp;Lucas Pizzuti","doi":"10.1016/j.tetlet.2026.155981","DOIUrl":"10.1016/j.tetlet.2026.155981","url":null,"abstract":"<div><div>A practical and metal-free approach to 1-thiazolyl-1<em>H</em>-indazoles was developed starting from readily available <em>o</em>-fluorobenzaldehydes. The method involves initial condensation with thiosemicarbazide and 2-bromoacetophenone to form <em>o</em>-fluorobenzaldehyde thiazolylhydrazones, followed by base-promoted intramolecular cyclization through nucleophilic aromatic substitution. After optimization of conditions, the reaction showed broad functional group tolerance and clear substituent effects, with halogens (Br, Cl) outperforming additional F or NO₂ due to cleaner conversions and easier isolation. The transformation proved scalable; a gram-scale experiment confirmed its practicality and enabled subsequent C<img>Br functionalization of the indazole core, further underscoring the synthetic utility of this approach. Structural assignments were confirmed by HRMS, ¹H and ¹³C NMR, and single-crystal X-ray diffraction.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"177 ","pages":"Article 155981"},"PeriodicalIF":1.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Palladium-catalyzed regioselectivity CH acetoxylation of 4-phenylquinazoline","authors":"Mushou Cai,&nbsp;Tongtong Deng,&nbsp;Shifeng Xin,&nbsp;Hongjun Zhu","doi":"10.1016/j.tetlet.2026.155974","DOIUrl":"10.1016/j.tetlet.2026.155974","url":null,"abstract":"<div><div>An efficient quinazoline-assisted <em>ortho-</em>acetoxylation of 4-phenylquinazoline has been developed using PhI(OAc)₂ as both the oxidizing agent and acetoxy source under Pd(II)-catalyzed C<img>H activation. The protocol exhibits high regioselectivity and functional group tolerance with yields up to 98%. Radical scavenging experiments indicate that the acetoxylation involves an acetoxy radical pathway.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"177 ","pages":"Article 155974"},"PeriodicalIF":1.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146025488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ring-opening of 3-substituted azetidines as an entry to triazolodiazepines","authors":"Melvin Raulin,&nbsp;Bruno Drouillat,&nbsp;Jérome Marrot,&nbsp;François Couty,&nbsp;Karen Wright","doi":"10.1016/j.tetlet.2026.155975","DOIUrl":"10.1016/j.tetlet.2026.155975","url":null,"abstract":"<div><div>Prochiral 3-substituted azetidines bearing a chiral <em>N</em>-substituent may undergo ring-opening reactions with electrophiles, such as benzyl or propargyl bromide, to generate diastereomeric products with moderate selectivity. In the case of the resulting 3-bromo-<em>N</em>-propargylamines, reaction with sodium azide followed by intramolecular azide-alkyne cycloaddition led to substituted tetrahydro triazolodiazepine derivatives. These findings expand the utility of azetidine scaffolds for the construction of more complex nitrogen-containing heterocycles.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"177 ","pages":"Article 155975"},"PeriodicalIF":1.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146025508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the toolbox of CH functionalization: the emergence of DMIX-substituted hypervalent iodine reagents","authors":"Qilong Lv,&nbsp;Yanchuan Zhao","doi":"10.1016/j.tetlet.2026.155979","DOIUrl":"10.1016/j.tetlet.2026.155979","url":null,"abstract":"<div><div>C<img>H functionalization has emerged as a powerful strategy in modern organic synthesis, enabling direct transformations of simple hydrocarbons into structurally diverse and value-added molecules. Among various approaches, diaryliodonium salts represent versatile intermediates that can be directly prepared from arenes and subsequently coupled with a wide range of nucleophiles, providing an efficient platform for rapid molecular diversification. However, one-step C<img>H functionalization to access diaryliodonium salts often suffers from narrow substrate scope, while the ensuing coupling reactions are hampered by limitations in aryl transfer selectivity. These challenges have constrained the broader application of this methodology. Recent advances in the design of 3,5-dimethylisoxazol-4-yl (DMIX)-substituted hypervalent iodine reagents have simultaneously overcome both substrate and selectivity limitations, offering new opportunities for expanding the utility of diaryliodonium salts in C<img>H functionalization. This review highlights the discovery and properties of DMIX-based reagents, and surveys their latest applications in achieving structurally diverse C<img>H functionalization, highlighting their potential to advance the field of hypervalent iodine chemistry.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"177 ","pages":"Article 155979"},"PeriodicalIF":1.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methanesulfonic acid-mediated direct synthesis of N-aryl-substituted pyrrolidines from amides","authors":"Tongming Niu ,&nbsp;Zhimin Sun ,&nbsp;Huijie Zhang ,&nbsp;Dexin Fu ,&nbsp;Qingbin Liu","doi":"10.1016/j.tetlet.2026.155973","DOIUrl":"10.1016/j.tetlet.2026.155973","url":null,"abstract":"<div><div>A metal-free protocol using methanesulfonic acid as an efficient mediator was successfully developed for the synthesis of <em>N</em>-aryl-substituted pyrrolidines from amides and tetrahydrofuran. Notably, the cyclic ethers were employed in a dual role as both reactants and reaction medium, which enhances their practicality. Systematic optimization revealed remarkable versatility, demonstrating broad substrate scope encompassing both aliphatic and aromatic amide derivatives.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"177 ","pages":"Article 155973"},"PeriodicalIF":1.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146025487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gentianellin A, an unusual immunosuppressive sesterterpenoid from the traditional Tibetan medicine Gentianella azurea","authors":"Xiao-Yu Qi ,&nbsp;Yu-Zhou Fan ,&nbsp;An-Yu Li ,&nbsp;Xue-Fei Li ,&nbsp;Jia-Mei Tang ,&nbsp;Yuan-Liang Xu ,&nbsp;Yan Liu ,&nbsp;Xue-Mei Niu ,&nbsp;Kai Guo ,&nbsp;Sheng-Hong Li","doi":"10.1016/j.tetlet.2026.155972","DOIUrl":"10.1016/j.tetlet.2026.155972","url":null,"abstract":"<div><div>Gentianellin A (<strong>1</strong>), a new gentianellane-type sesterterpenoid possessing a 5/7/5/6/5 pentacyclic ring system formed by a bridged ether bond, was isolated from the traditional Tibetan medicine <em>Gentianella azurea</em>. Its structure was elucidated by extensive spectroscopic analysis, single-crystal X-ray diffraction, and quantum chemical calculations. Compound <strong>1</strong> exhibited immunosuppressive activity by inhibiting the secretion of IL-6 and TNF-α in LPS-induced macrophages RAW264.7 with IC₅₀ values of 13.80 and 18.46 μM.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"177 ","pages":"Article 155972"},"PeriodicalIF":1.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145993575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cleavage of benzyl esters by diiodine–triethylsilane system","authors":"Jin Jiang ,&nbsp;Zhuo Wang ,&nbsp;Lili Xiao","doi":"10.1016/j.tetlet.2026.155980","DOIUrl":"10.1016/j.tetlet.2026.155980","url":null,"abstract":"<div><div>A method for the debenzylation of benzyl esters has been developed, utilizing easy-to-operate diiodine and triethylsilane. This procedure can be carried out in an air atmosphere at room temperature, without the need for transition metals or hydrogen. Halogen, hydroxyl, methoxy, ester, nitro and other functional groups are compatible with this debenzylation.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"177 ","pages":"Article 155980"},"PeriodicalIF":1.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photochemical cross-coupling between sulfenyl chlorides and thiols: a facile, catalyst- and additive-free access to unsymmetrical disulfides","authors":"Wei Liu ,&nbsp;Xiaoning Yang ,&nbsp;Jiayi Wang ,&nbsp;Gonghua Song","doi":"10.1016/j.tetlet.2026.155977","DOIUrl":"10.1016/j.tetlet.2026.155977","url":null,"abstract":"<div><div>A novel, environmentally friendly and highly efficient protocol has been developed for the synthesis of unsymmetrical disulfides <em>via</em> a photochemical radical cross-coupling reaction between sulfenyl chlorides and thiols under LED irradiation. The process does not need any catalyst or additive. The high-yield recovery of the solvent and the primary by-product makes this method highly atom-economical.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"177 ","pages":"Article 155977"},"PeriodicalIF":1.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in Friedel-Crafts reaction of isopiperitenol (2005–2025): concise way to synthesize bioinspired indole-fused polycycles and cannabinoids","authors":"Amar Nath Singh Chauhan,&nbsp;Omkar S. Dalvi,&nbsp;Rohan D. Erande","doi":"10.1016/j.tetlet.2026.155978","DOIUrl":"10.1016/j.tetlet.2026.155978","url":null,"abstract":"<div><div>Cannabinoids and indole–fused polycyclic natural products constitute a structurally diverse class of compounds possessing substantial pharmacological and industrial relevance. Multiple stereocenters, polycyclic frameworks, and sensitive functional groups pose persistent synthetic challenges, particularly for stereocontrolled access to their single enantiomers. Over the past two decades, promising synthetic pursuits, including Lewis acids catalyzed Friedel Crafts alkylation, chiral pool synthesis, terpene derivatization, biomimetic cyclizations, and Brønsted acid catalysis have enabled efficient as well as scalable synthetic routes to these complex scaffolds. These approaches not only allowed efficient synthesis of indole alkaloids such as murrayamines, hapalindoles, fischerindoles, and natural cannabinoids such as Δ⁹-THC, Δ⁸-THC, CBD, CBDV, CBDP, CBD-Hex, CBD-Oct, machaeriols, and <em>epi</em>-machaeriols, but also facilitated systematic exploration of stereochemistry for these natural products. By integrating synthetic protocols with structural–activity relationships, these strategies provided a versatile platform for designing next-generation analogues with tailored pharmacological profiles and industrial applications. This review highlights the recent advances (2005–2025) in Friedel–Crafts-driven synthetic strategies for efficiently constructing cannabinoids and indole–fused polycyclic scaffolds commenced from isopiperitenol, presenting the first unified compilation of targeted natural products derived from this versatile and readily accessible starting material. This comprehensive review emphasizes stereocontrolled, protecting-group-free, and scalable methods, including chiral pool synthesis, biomimetic cyclizations, and confined Brønsted acid catalysis, discussing synthetic pursuits and structure–activity relationships. Further, the review is systematically classified into five subsections 1] Introduction, 2] Aim and scope of review 3] Synthetic approaches 4] Conceptual framework and designing principles and 5] Conclusion.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"177 ","pages":"Article 155978"},"PeriodicalIF":1.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}