Pub Date : 2024-10-15DOI: 10.1016/j.tetlet.2024.155327
The alkylation of tetrazole and acetone under the catalysis of TfOH has been shown to be an efficient process with high levels of regioselective control. This protocol features simple and readily accessible starting materials, unique reaction mechanism, excellent compatibility with diverse functional groups.
{"title":"Brønsted acid-catalyzed selective alkylation of tetrazoles with acetone","authors":"","doi":"10.1016/j.tetlet.2024.155327","DOIUrl":"10.1016/j.tetlet.2024.155327","url":null,"abstract":"<div><div>The alkylation of tetrazole and acetone under the catalysis of TfOH has been shown to be an efficient process with high levels of regioselective control. This protocol features simple and readily accessible starting materials, unique reaction mechanism, excellent compatibility with diverse functional groups.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432879","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}
Pub Date : 2024-10-15DOI: 10.1016/j.tetlet.2024.155323
Two new isoledene-type sesquiterpenoids, 1 and 2, were isolated from an Okinawan soft coral Heteroxenia sp. The planar structures and stereochemistry of 1 and 2 were determined by spectroscopic analysis, X-ray crystallography, and comparison of experimental and calculated ECD studies. Antiviral and anti-leishmania assays were performed. Compound 2 exhibited activity against promastigotes of Leishmania major.
{"title":"Two isoledene-type sesquiterpenoids from a soft coral Heteroxenia sp.","authors":"","doi":"10.1016/j.tetlet.2024.155323","DOIUrl":"10.1016/j.tetlet.2024.155323","url":null,"abstract":"<div><div>Two new isoledene-type sesquiterpenoids, <strong>1</strong> and <strong>2</strong>, were isolated from an Okinawan soft coral <em>Heteroxenia</em> sp. The planar structures and stereochemistry of <strong>1</strong> and <strong>2</strong> were determined by spectroscopic analysis, X-ray crystallography, and comparison of experimental and calculated ECD studies. Antiviral and anti-leishmania assays were performed. Compound <strong>2</strong> exhibited activity against promastigotes of <em>Leishmania major</em>.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446919","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}
Pub Date : 2024-10-14DOI: 10.1016/j.tetlet.2024.155322
Fifteen new bis-pyrrolo[3,4-b]pyridin-5-ones were synthesized via a one-pot process composed by a pseudo-repetitive Ugi-Zhu-5CR coupled to a double cascade sequence (aza-Diels-Alder cycloaddition/N-acylation/decarboxylation/dehydration) in 39–77 % yields, and in short reaction times (only one hour per compound) despite the big size, symmetry and high complexity of the products. The reaction conditions were first optimized step-by-step, and then, the bis-heterocyclic products were synthesized in one-pot manner. It was observed that, formation of the corresponding imines and the double cascade process were carried out without external heating inputs, instead that only under constant stirring at room temperature. Reaction conditions turned out to be the friendliest (in terms of energy) with the environment in comparison with all previously published methodologies involving post-Ugi-Zhu reactions. Therefore, this work shows that pseudo-repetitive MCRs are more thermodynamically favorable compared to classic MCRs, and that they also allow rapid access to highly structurally complex molecules, exhibiting a high degree of symmetry that may play an important role in several fields of knowledge like optics, material science, agrochemistry, and medicinal chemistry.
{"title":"One-pot synthesis of phenyl- and biphenyl-linked bis-pyrrolo[3,4-b]pyridin-5-ones via a pseudo-repetitive Ugi-Zhu-5CR coupled to a double cascade process (aza-Diels-Alder/N-acylation/decarboxylation/dehydration)","authors":"","doi":"10.1016/j.tetlet.2024.155322","DOIUrl":"10.1016/j.tetlet.2024.155322","url":null,"abstract":"<div><div>Fifteen new <em>bis</em>-pyrrolo[3,4-<em>b</em>]pyridin-5-ones were synthesized <em>via</em> a one-pot process composed by a pseudo-repetitive Ugi-Zhu-5CR coupled to a double cascade sequence (<em>aza</em>-Diels-Alder cycloaddition/<em>N</em>-acylation/decarboxylation/dehydration) in 39–77 % yields, and in short reaction times (only one hour per compound) despite the big size, symmetry and high complexity of the products. The reaction conditions were first optimized step-by-step, and then, the <em>bis</em>-heterocyclic products were synthesized in one-pot manner. It was observed that, formation of the corresponding imines and the double cascade process were carried out without external heating inputs, instead that only under constant stirring at room temperature. Reaction conditions turned out to be the friendliest (in terms of energy) with the environment in comparison with all previously published methodologies involving post-Ugi-Zhu reactions. Therefore, this work shows that pseudo-repetitive MCRs are more thermodynamically favorable compared to classic MCRs, and that they also allow rapid access to highly structurally complex molecules, exhibiting a high degree of symmetry that may play an important role in several fields of knowledge like optics, material science, agrochemistry, and medicinal chemistry.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446861","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}
Pub Date : 2024-10-14DOI: 10.1016/j.tetlet.2024.155325
The requirement for scaffolds has prompted synthetic chemists to devise simple and effective methods for optimal synthesis, which are critical in the medical industry. Under comparatively optimized conditions, a click followed by a CC bond coupling reaction between iodoalkyne (4) and substituted nitrile oxide was utilized to explore the synthesis of fused isoxazoles containing thiopyrano[2,3-d]pyrimidine under microwave irradiation. The synthesized compounds were tested for their anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H460 and A549). The compounds 6i and 6l have shown more potent activity against both cancer cell lines as compared to standard drugs doxorubicin and erlotinib. And also compounds 6e, 6j, and 6k have shown more potent activity as compared to Doxorubicin and moderate activity compared to erlotinib. Later, in vitro EGFR results of more potent compounds revealed that compounds 6l and 6k have shown potent EGFR activity compared to standard erlotinib. To evaluate the molecular interactions of more potent compounds with the human epidermal growth factor receptor. It was observed that all the potent compounds exhibited greater binding energies in comparison to the standard drug erlotinib.
{"title":"One-pot synthesis of fused isoxazolo[4′,5′:4,5]thiopyrano[2,3-d]pyrimidines as potent EGFR targeting anti-lung cancer agents","authors":"","doi":"10.1016/j.tetlet.2024.155325","DOIUrl":"10.1016/j.tetlet.2024.155325","url":null,"abstract":"<div><div>The requirement for scaffolds has prompted synthetic chemists to devise simple and effective methods for optimal synthesis, which are critical in the medical industry. Under comparatively optimized conditions, a click followed by a C<img>C bond coupling reaction between iodoalkyne (4) and substituted nitrile oxide was utilized to explore the synthesis of fused isoxazoles containing thiopyrano[2,3-<em>d</em>]pyrimidine under microwave irradiation. The synthesized compounds were tested for their anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H460 and A549). The compounds <strong>6i</strong> and <strong>6l</strong> have shown more potent activity against both cancer cell lines as compared to standard drugs doxorubicin and erlotinib. And also compounds <strong>6e</strong>, <strong>6j</strong>, and <strong>6k</strong> have shown more potent activity as compared to Doxorubicin and moderate activity compared to erlotinib. Later, <em>in vitro</em> EGFR results of more potent compounds revealed that compounds <strong>6l</strong> and <strong>6k</strong> have shown potent EGFR activity compared to standard erlotinib. To evaluate the molecular interactions of more potent compounds with the human epidermal growth factor receptor. It was observed that all the potent compounds exhibited greater binding energies in comparison to the standard drug erlotinib.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441420","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}
Pub Date : 2024-10-14DOI: 10.1016/j.tetlet.2024.155324
A method for the synthesis of new 7-(substituted amino)-5-methylthioazolo[1,5-a]pyrimidines has been developed. Based on the MTT test, IC50 values were calculated for the obtained compounds against lung carcinoma (A549), liver carcinoma (HepG2), embryonal rhabdomyosarcoma (Rd) and human embryonic kidney (HEK 293) cell lines. Some compounds from the series demonstrated activity close to the reference drug, but with a certain selectivity. Based on the results of MTT assay and molecular docking studies for the catalytic subunits of PI3K, two isoforms (PI3Kβ and PI3Kδ) were assumed as the targets for the new series of azolo[1,5-a]pyrimidines with cytotoxic effect on the rhabdomyosarcoma cell line.
{"title":"7-(Substituted amino)-5-methylthioazolo[1,5-a]pyrimidines: Synthesis, cytotoxic properties in vitro and molecular docking","authors":"","doi":"10.1016/j.tetlet.2024.155324","DOIUrl":"10.1016/j.tetlet.2024.155324","url":null,"abstract":"<div><div>A method for the synthesis of new 7-(substituted amino)-5-methylthioazolo[1,5-<em>a</em>]pyrimidines has been developed. Based on the MTT test, IC<sub>50</sub> values were calculated for the obtained compounds against lung carcinoma (A549), liver carcinoma (HepG2), embryonal rhabdomyosarcoma (Rd) and human embryonic kidney (HEK 293) cell lines. Some compounds from the series demonstrated activity close to the reference drug, but with a certain selectivity. Based on the results of MTT assay and molecular docking studies for the catalytic subunits of PI3K, two isoforms (PI3Kβ and PI3Kδ) were assumed as the targets for the new series of azolo[1,5-<em>a</em>]pyrimidines with cytotoxic effect on the rhabdomyosarcoma cell line.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441419","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}
Pub Date : 2024-10-12DOI: 10.1016/j.tetlet.2024.155320
A metal-free and one-pot procedure for thioarylation of uracils and in situ generated enaminones with thiols in the presence of C2Cl6 is introduced. This protocol is a less toxic alternative to other conventional thioarylation techniques because it uses hexachloroethane as a solid oxidant, which is stable, inexpensive, readily available and easier to work with.
{"title":"Metal-free CH thioarylation of uracils and in situ generated enaminones using thiols in the presence of hexachloroethane","authors":"","doi":"10.1016/j.tetlet.2024.155320","DOIUrl":"10.1016/j.tetlet.2024.155320","url":null,"abstract":"<div><div>A metal-free and one-pot procedure for thioarylation of uracils and <em>in situ</em> generated enaminones with thiols in the presence of C<sub>2</sub>Cl<sub>6</sub> is introduced. This protocol is a less toxic alternative to other conventional thioarylation techniques because it uses hexachloroethane as a solid oxidant, which is stable, inexpensive, readily available and easier to work with.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417330","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}
Pub Date : 2024-10-11DOI: 10.1016/j.tetlet.2024.155328
Herein we report an efficient and convenient method for synthesizing 1H-benzo[d]imidazoles via a base-promoted reaction of readily available α-CF3 ketone-derived hydrazones with o-phenylenediamines. The key innovation is the anion-driven triple-cleavage of the CF bond in the CF3 group, which acts as a C1 synthon at the 2-position of the 1H-benzo[d]imidazole. This novel approach simplifies the synthesis and can be extended to the preparation of benzo[d]oxazoles and benzo[d]thiazoles. Our method offers a versatile and robust platform for the synthesis of important heterocyclic compounds, with potential applications in medicinal chemistry and drug discovery.
{"title":"Anion-driven CF bond cleavage of trifluoromethyl N-aryl hydrazones toward the assembly of N-heterocycles","authors":"","doi":"10.1016/j.tetlet.2024.155328","DOIUrl":"10.1016/j.tetlet.2024.155328","url":null,"abstract":"<div><div>Herein we report an efficient and convenient method for synthesizing 1<em>H</em>-benzo[<em>d</em>]imidazoles via a base-promoted reaction of readily available α-CF<sub>3</sub> ketone-derived hydrazones with <em>o</em>-phenylenediamines. The key innovation is the anion-driven triple-cleavage of the C<img>F bond in the CF<sub>3</sub> group, which acts as a C1 synthon at the 2-position of the 1<em>H</em>-benzo[<em>d</em>]imidazole. This novel approach simplifies the synthesis and can be extended to the preparation of benzo[<em>d</em>]oxazoles and benzo[<em>d</em>]thiazoles. Our method offers a versatile and robust platform for the synthesis of important heterocyclic compounds, with potential applications in medicinal chemistry and drug discovery.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441469","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}
Pub Date : 2024-10-11DOI: 10.1016/j.tetlet.2024.155321
Oxidative activation of CO, CN and CC bonds has recently emerged as a powerful method for the synthesis of valuable organic compounds. However, these strategies have often required the metal catalysts and strong external oxidants. Herein, we report a new protocol for the convenient construction of vinyl sulfoxides from phenylglycinols and DMSO under basic conditions. Notably, DMSO was used not only as a methyl sulfoxide (−SOMe) reagent, but also as an oxidizing agent. The present system features mild metal- and external oxidant-free conditions, broad scope, and excellent functionality tolerance.
近来，CO、CN 和 CC 键的氧化活化已成为合成有价值有机化合物的有力方法。然而，这些方法通常需要金属催化剂和强外部氧化剂。在此，我们报告了一种在碱性条件下利用苯基甘氨醇和二甲基亚砜方便地构建乙烯基硫醚的新方法。值得注意的是，DMSO 不仅用作甲基亚砜 (-SOMe) 试剂，还用作氧化剂。本系统的特点是条件温和，不含金属和外部氧化剂，适用范围广，对官能度的耐受性极佳。
{"title":"Facile synthesis of vinyl sulfoxides via external oxidant-free oxidative condensation of phenylglycinols with DMSO","authors":"","doi":"10.1016/j.tetlet.2024.155321","DOIUrl":"10.1016/j.tetlet.2024.155321","url":null,"abstract":"<div><div>Oxidative activation of C<img>O, C<img>N and C<img>C bonds has recently emerged as a powerful method for the synthesis of valuable organic compounds. However, these strategies have often required the metal catalysts and strong external oxidants. Herein, we report a new protocol for the convenient construction of vinyl sulfoxides from phenylglycinols and DMSO under basic conditions. Notably, DMSO was used not only as a methyl sulfoxide (−SOMe) reagent, but also as an oxidizing agent. The present system features mild metal- and external oxidant-free conditions, broad scope, and excellent functionality tolerance.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446925","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}
Pub Date : 2024-10-05DOI: 10.1016/j.tetlet.2024.155310
An anti-Markovnikov difluoroacetamidation of α-(trifluoromethyl)styrenes was successfully performed, yielding 2,2,5,5,5-pentafluoropentanamides in good yields. This reaction was catalyzed by CuBr in the presence of pentamethyldiethylenetriamine (PMDETA) in MeCN, conducted under a nitrogen atmosphere. To assess the influence of substituent groups on the aromatic ring, two series of substrates were tested within the developed catalytic system. Additionally, scale-up applications and mechanistic studies were carried out.
{"title":"Practical cuprous catalyzed anti-Markovnikov difluoroacetamidation of α-(trifluoromethyl)styrenes","authors":"","doi":"10.1016/j.tetlet.2024.155310","DOIUrl":"10.1016/j.tetlet.2024.155310","url":null,"abstract":"<div><div>An anti-Markovnikov difluoroacetamidation of α-(trifluoromethyl)styrenes was successfully performed, yielding 2,2,5,5,5-pentafluoropentanamides in good yields. This reaction was catalyzed by CuBr in the presence of pentamethyldiethylenetriamine (PMDETA) in MeCN, conducted under a nitrogen atmosphere. To assess the influence of substituent groups on the aromatic ring, two series of substrates were tested within the developed catalytic system. Additionally, scale-up applications and mechanistic studies were carried out.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417327","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}
Pub Date : 2024-10-03DOI: 10.1016/j.tetlet.2024.155319
A diverse array of functionalized indolo[2,1-a]isoquinolines are constructed through an NHC-catalyzed transition-metal-, and oxidant-free radical tandem cyclization from readily accessible 2-aryl N-methacryloyl indoles and α-bromo esters. This redox-neutral protocol exhibits a wide substrate scope, excellent functional group tolerance, and can be scaled up to 2.0 mmol with parallel efficiency. Mechanistic studies suggest that a single electron transfer radical process is likely involved.
{"title":"Transition-metal-free tandem cyclization by radical NHC catalysis: Rapid access to indolo[2,1‑a]isoquinolines","authors":"","doi":"10.1016/j.tetlet.2024.155319","DOIUrl":"10.1016/j.tetlet.2024.155319","url":null,"abstract":"<div><div>A diverse array of functionalized indolo[2,1-<em>a</em>]isoquinolines are constructed through an NHC-catalyzed transition-metal-, and oxidant-free radical tandem cyclization from readily accessible 2-aryl N-methacryloyl indoles and α-bromo esters. This redox-neutral protocol exhibits a wide substrate scope, excellent functional group tolerance, and can be scaled up to 2.0 mmol with parallel efficiency. Mechanistic studies suggest that a single electron transfer radical process is likely involved.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417328","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}
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