Tetrahedron最新文献

英文中文

Trichoglutamides A to C from yellow Tricholoma species 来自黄色毛喉类的毛喉酰胺 A 至 C

IF 2.1 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron

Pub Date : 2024-09-20 DOI: 10.1016/j.tet.2024.134276

Yumiko Oba , Yuri Nakamura , Mitsuru Kondo , Jing Wu , Makoto Urai , Motohiro Tomizawa , Hirokazu Kawagishi , Kimiko Hashimoto

Three novel compounds 1 to 3, named trichoglutamides A to C, respectively, were isolated from the fruiting bodies of yellow Tricholoma species, T. flavovirens, T. auratum, and T. sulphureum. Their structures were determined by the interpretation of spectroscopic data and by X-ray crystallographic analysis. The structure of trichoglutamide consists of a glutamic acid residue and a C-10 polyketide unit.

从黄色毛果芸香科植物 T. flavovirens、T. auratum 和 T. sulphureum 的子实体中分离出三种新型化合物 1 至 3，分别命名为毛果芸香酰胺 A 至 C。通过解释光谱数据和 X 射线晶体分析确定了它们的结构。Trichoglutamide 的结构由一个谷氨酸残基和一个 C-10 聚酮单元组成。

引用次数: 0

DMSO suppresses duclauxin biosynthetic pathway in Talaromyces sp. (strain IQ-313) and untaps terpenoids, polyketides and meroterpenoids biosynthesis DMSO 可抑制 Talaromyces sp.（菌株 IQ-313）的杜仲苷生物合成途径，并解除萜类化合物、多酮类化合物和经萜类化合物的生物合成过程

IF 2.1 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron

Pub Date : 2024-09-20 DOI: 10.1016/j.tet.2024.134283

Enrique Aguilar-Ramírez, José Rivera-Chávez, Valeria Abogado-Aponte, Beatriz Quiroz-García, Adriana Romo-Pérez

Talaromyces sp. (strain IQ-313) produces duclauxin-type molecules under standard fermentation conditions in rice and oat cereal. Such molecules are of great interest due to their structural complexity and biological activity. Interestingly, application of an OSMAC (One Strain Many Compounds) approach, revealed that the biosynthetic machinery of this fungus can be directed towards the production of other types of molecules, while completely suppressing the biosynthesis of duclauxin (1). To exploit the metabolic potential of Talaromyces sp. (strain IQ-313), it was grown on solid media supplemented with dimethyl sulfoxide (DMSO), an ectopic epigenetic modulator. Metabolomic analysis of the fermentation extract from the strain grown under standard and DMSO-supplemented conditions, using molecular networking, revealed notable differences in the profiles. Chemical investigation of the extract obtained under abiotic stress led to the isolation and characterization of 15 molecules not detected under standard conditions, including nine polyketides, one sesquiterpenoid, two sesterterpenoids, and three meroterpenoids. Among these, talaromophilane (2), an eremophilane sesquiterpenoid, and talaroisochromane (8), an oxoisochromen, have not been previously reported in the literature. The structures of all isolates were established using a combination of spectroscopic and spectrometric data. The absolute configuration of compound 2 was established based on the analysis of NOESY interactions and by comparison of the experimental and theoretical electronic circular dichroism (ECD) curves.

Talaromyces sp.（菌株 IQ-313）在大米和燕麦谷物中的标准发酵条件下产生杜冷丁类分子。这类分子因其结构的复杂性和生物活性而备受关注。有趣的是，应用 OSMAC（一种菌株多种化合物）方法发现，这种真菌的生物合成机制可以定向用于生产其他类型的分子，同时完全抑制杜冷丁的生物合成（1）。为了开发塔拉酵母菌（菌株 IQ-313）的代谢潜力，研究人员在固体培养基中添加了二甲基亚砜（DMSO）（一种异位表观遗传调节剂）。利用分子网络对菌株在标准条件下和添加二甲基亚砜条件下的发酵提取物进行代谢组学分析，发现两者的代谢组学特征存在明显差异。通过对非生物胁迫条件下提取物的化学研究，分离并鉴定了 15 种在标准条件下未检测到的分子，包括 9 种多酮类化合物、1 种倍半萜类化合物、2 种酯萜类化合物和 3 种经萜类化合物。其中，talaromophilane (2)（一种eremophilane倍半萜类化合物）和talaroisochromane (8)（一种oxoisochromen类化合物）以前从未在文献中报道过。所有分离物的结构都是通过光谱和分光数据相结合的方法确定的。化合物 2 的绝对构型是根据 NOESY 相互作用的分析以及实验和理论电子圆二色性曲线的比较确定的。

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引用次数: 0

Exploring the reaction mechanistic pathway for the sensing of G-Series nerve agent with Kemp's triacid derivative: A computational study 探索坎普三酸衍生物感知 G 系列神经毒剂的反应机理途径：计算研究

IF 2.1 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron

Pub Date : 2024-09-20 DOI: 10.1016/j.tet.2024.134281

Dipankar Das , Bishwajit Ganguly

Kemp's triacid derivative have been reported as a candidate for sensing of nerve agents employing the photoinduced electron transfer (PET) processes. The sensor probe molecules were prepared with primary alcohol in very close proximity to a tertiary amine to acylate the alcohol with rapid intramolecular N-alkylation to produce quaternary ammonium salt. The reaction pathways for the formation of quaternary ammonium salt and isomethyl propyl phosphonate remain unexplored. In this report, the mechanistic pathways of G-series nerve agents sarin and its simulant diethylcholorophosphate (DCP) with Kemp's triacid derivatives has been explored computationally. The calculations performed with B3LYP-D3/6-311+G(d,p) level of theory in DCM solvent revealed that the reaction proceeds via intermolecular and intramolecular S_N2 pathways. The probe molecule is sterically hindered, therefore, the frontside and backside S_N2 reaction pathways have been examined. The computed results suggest that the first intermolecular S_N2 reaction of Kemp's triacid derivatives (I & II) with sarin for the backside attack is energetically favored compared to the frontside attack and the following intramolecular S_N2 reaction is a barrierless process. The calculations performed with simulant diethylcholorophosphate (DCP) and Kemp's triacid derivatives (I & II) show that the reactions are energetically more facile compared to the nerve agent sarin molecule. The Distortion-Interaction model and ΔNBOSteric analysis showed that the back side is energetically favored over the front side attack in such S_N2 reactions. The designed Kemp's triacid derivative (II) with phosphorus center for sensing sarin and (DCP) suggests that the size of the hetero centers are important to facilitate the reaction in the probe molecule.

据报道，坎普三酸衍生物是利用光诱导电子转移（PET）过程感测神经毒剂的候选物质。在制备传感器探针分子时，伯醇非常靠近叔胺，使伯醇酰化，并通过快速的分子内 N-烷基化反应生成季铵盐。季铵盐和丙基膦酸异甲酯的生成反应途径仍未探明。本报告通过计算探索了 G 系列神经毒剂沙林及其模拟物二乙基胆磷酸酯（DCP）与坎普三酸衍生物的机理途径。在 DCM 溶剂中用 B3LYP-D3/6-311+G(d,p) 理论水平进行的计算表明，反应是通过分子间和分子内 SN2 途径进行的。探针分子受到立体阻碍，因此研究了前侧和后侧 SN2 反应途径。计算结果表明，坎普三酸衍生物（I & II）与沙林的第一次分子间 SN2 反应的背面攻击在能量上比正面攻击有利，而接下来的分子内 SN2 反应则是一个无障碍过程。用模拟物二乙基胆磷酸酯（DCP）和坎普三酸衍生物（I & II）进行的计算表明，与神经毒剂沙林分子相比，这些反应在能量上更为容易。畸变-相互作用模型和ΔNBOSteric分析表明，在此类SN2反应中，背面攻击在能量上比正面攻击更有利。设计出的带有磷中心的 Kemp's 三酸衍生物 (II) 可感知沙林和 (DCP)，这表明杂中心的大小对于促进探针分子中的反应非常重要。

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引用次数: 0

Desulfonation-associated direct amide bond formation between N-sulfonyl-1,2,3-triazoles with carboxylic acids N-磺酰基-1,2,3-三唑与羧酸之间脱磺相关的直接酰胺键形成

IF 2.1 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron

Pub Date : 2024-09-19 DOI: 10.1016/j.tet.2024.134268

Zongjing Hu , Yaqi Deng , Jian Ji , Jinhua Liu , Yun Zhao , Shunying Liu , Shi-Hua Luo

We have developed a highly N²-regioselective method for direct construction of amide bond from N-sulfonyl-1,2,3-triazoles and carboxylic acids in the presence of bases at 60 °C in air. The developed reaction provides the corresponding products with high yields (up to 90 %) and a broad substrate compatibility including aryl acids, heterocyclic acids, and alkyl acids. Mechanistic studies show that the reaction proceeds through a direct nucleophilic attack of N-sulfonyl-1,2,3-triazoles to carboxylate anions via a base- and water-involved synergistic desulfonation process. This work presents an unusual water-involved example for direct synthesis of amides utilizing readily available starting materials under mild conditions.

我们开发了一种高度 N2 区域选择性的方法，用于在 60 °C 空气中，在碱存在的条件下，由 N-磺酰基-1,2,3-三唑和羧酸直接构建酰胺键。所开发的反应可提供相应的产物，且产率高（高达 90%），并具有广泛的底物兼容性，包括芳基酸、杂环酸和烷基酸。机理研究表明，该反应是通过 N-磺酰基-1,2,3-三唑对羧酸根阴离子的直接亲核攻击，经由碱和水参与的协同脱硫过程进行的。这项研究为在温和条件下利用容易获得的起始材料直接合成酰胺提供了一个不同寻常的水参与实例。

引用次数: 0

Physicochemical properties and cytochromes P-450 kinetics of 5,5-bis(4-fluorophenyl)imidazolidine-2,4-dione, the bis(para-fluorophenyl) derivative of phenytoin 5,5-双（4-氟苯基）咪唑烷-2,4-二酮（苯妥英的双（对氟苯基）衍生物）的理化性质和细胞色素 P-450 动力学

IF 2.1 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron

Pub Date : 2024-09-19 DOI: 10.1016/j.tet.2024.134275

Presley C. Cole, Briana I. Martinez, Thomas A. Shell

Phenytoin (PHT, brand name: Dilantin) is an anticonvulsant drug that is used in the treatment of epilepsy. PHT is metabolically inactivated by cytochromes P-450 (CYP) catalyzed aromatic hydroxylation at the para position. Therefore, Nelson et al. hypothesized that this metabolic pathway would be slowed or blocked for a PHT derivative with fluorines at the para positions of the aromatic rings (pF-PHT) resulting in a molecule with increased antiseizure activity and longer duration of action relative to PHT. Interestingly, pF-PHT is less active than PHT, but has a much longer duration of action. Nelson et al. hypothesized that differences in physicochemical properties must contribute to the poor activity of pF-PHT. Thus, pF-PHT was synthesized to compare its physicochemical properties with those of PHT. In addition, the kinetics of CYP catalyzed oxidation were compared using Sprague Dawley (SD) rat liver microsomes because PHT is metabolically inactivated by CYP in the liver. The previously reported synthesis of pF-PHT employs a highly toxic reagent and produces a highly poisonous gas. Therefore, a safer synthetic route for pF-PHT was developed. This synthetic approach utilizes three steps: 1) a thiamine catalyzed benzoin condensation of para-fluorobenzaldehyde, 2) a nitric acid oxidation of the benzoin product to the corresponding benzil derivative, and 3) a microwave-assisted phenytoin synthesis of this benzil derivative with urea. There are no significant differences in conjugation, acidity, and lipophilicity between PHT and pF-PHT. Therefore, our results do not support the hypothesis that the low activity of pF-PHT relative to PHT results from variations in physicochemical properties. While PHT and pF-PHT have the same apparent binding affinity for the CYP proteome of the SD rat liver microsome, pF-PHT undergoes CYP catalyzed oxidation at half the rate in comparison to PHT.

苯妥英（PHT，品牌名：Dilantin）是一种抗惊厥药物，用于治疗癫痫。PHT 通过细胞色素 P-450 (CYP) 催化芳香族对位羟基化作用而代谢失活。因此，Nelson 等人假设，芳香环对位含氟的 PHT 衍生物（pF-PHT）会减慢或阻断这种代谢途径，从而产生一种抗癫痫活性更强、作用时间比 PHT 更长的分子。有趣的是，pF-PHT 的活性低于 PHT，但作用时间却更长。Nelson 等人推测，pF-PHT 活性低的原因肯定是理化性质的差异。因此，他们合成了 pF-PHT，以比较其与 PHT 的理化性质。此外，由于 PHT 在肝脏中会被 CYP 代谢灭活，因此还使用 Sprague Dawley（SD）大鼠肝脏微粒体对 CYP 催化氧化的动力学进行了比较。之前报道的 pF-PHT 合成方法使用了剧毒试剂并产生了剧毒气体。因此，我们开发了一种更安全的 pF-PHT 合成路线。这种合成方法分为三个步骤：1) 对氟苯甲醛在硫胺催化下进行安息香缩合；2) 安息香产物在硝酸氧化下生成相应的苯偶姻衍生物；3) 苯偶姻衍生物与尿素在微波辅助下进行苯妥英合成。PHT 和 pF-PHT 在共轭、酸度和亲油性方面没有明显差异。因此，我们的研究结果并不支持 pF-PHT 活性低于 PHT 是由于理化性质差异造成的这一假设。虽然 PHT 和 pF-PHT 与 SD 大鼠肝脏微粒体的 CYP 蛋白组具有相同的表面结合亲和力，但 pF-PHT 在 CYP 催化下的氧化速度只有 PHT 的一半。

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引用次数: 0

One-pot multi-component synthesis of 2-Amino-4H-chromenes catalyzed by a fiber super base under mild conditions 纤维超强碱在温和条件下催化的 2-氨基-4H-苯的一锅多组分合成

IF 2.1 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron

Pub Date : 2024-09-19 DOI: 10.1016/j.tet.2024.134282

Haitao Cui , Pengyu Li , Huijun Zhao , Yongqiang Chen , Yahui Yuan , Yuan Liu , Wenying Ai , Mingli Jiao

Heterogeneous catalysis is a crucial component of green chemistry. In this study, a series of polyacrylonitrile fiber (PANF) catalysts, specifically PANF-TBDs, were developed by immobilizing the commonly utilized super organic base 1,5,7-triazabicyclo [4.4.0] dec-5-ene (TBD) onto commercially accessible PANF. This novel catalyst facilitates the effective and eco-friendly one-pot synthesis of 2-amino-4H-chromene. Moreover, an investigation into the impact of modification density on the catalytic efficacy of PANF-TBDs have been conducted. It was observed that PANF-TBD(2.0) with a higher TBD graft density can yield exceptional results, even surpassing 96 %, in a mere 30 min at a mild temperature 30 °C when utilizing water as a green and easily available solvent. Furthermore, the catalyst can be effortlessly isolated from the reaction system and displays notable reusability for a minimum of 10 cycles without show obvious decline in performance.

异相催化是绿色化学的重要组成部分。在本研究中，通过将常用的超级有机碱 1,5,7- 三氮杂双环 [4.4.0] 癸-5-烯（TBD）固定在市售的聚丙烯腈纤维（PANF）上，开发了一系列聚丙烯腈纤维催化剂，特别是 PANF-TBD。这种新型催化剂有助于高效、环保地实现 2-氨基-4H-色烯的一锅合成。此外，还研究了改性密度对 PANF-TBD 催化效率的影响。结果表明，当使用水作为一种绿色且易于获得的溶剂时，具有较高 TBD 接枝密度的 PANF-TBD(2.0) 能在 30 °C 的温和温度下，在短短 30 分钟内产生卓越的效果，甚至超过 96%。此外，这种催化剂还可以毫不费力地从反应体系中分离出来，并可重复使用至少 10 个循环，而性能不会明显下降。

引用次数: 0

I2-promoted one-pot synthesis of 1,3,4-oxadiazoles from aroyl hydrazides and methyl/ethyl acetate I2 促进以芳基酰肼和乙酸甲酯/乙酯为原料单锅合成 1,3,4-噁二唑

IF 2.1 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron

Pub Date : 2024-09-19 DOI: 10.1016/j.tet.2024.134280

Jianxi Du , Qin Su , Ying-Ming Pan , Keyume Ablajan

This study aimed to propose an unprecedented I₂-promoted one-pot tandem synthesis of 1,3,4-oxadiazoles through the cyclization between aroyl hydrazides and methyl/ethyl acetate. A diverse array of 2-arylated 1,3,4-oxadiazoles and 5-methyl 1,3,4-oxadiazoles were successfully synthesized in good to excellent yields. The significant advantage of this protocol was its full exploitation of the principle of atomic economy, whereby the reactant served as the reaction solvent directly. Moreover, the reaction demonstrated a broad substrate scope, and the product was readily separable.

本研究旨在提出一种前所未有的 I2 促进的单锅串联合成 1,3,4-恶二唑的方法，即通过芳基酰肼和乙酸甲酯/乙酯之间的环化反应合成 1,3,4-恶二唑。成功合成了多种 2-芳基化的 1,3,4-恶二唑和 5-甲基 1,3,4-恶二唑，产率从良好到极佳。该方法的最大优点是充分利用了原子经济性原理，即反应物直接作为反应溶剂。此外，该反应的底物范围很广，而且产物很容易分离。

引用次数: 0

One-pot sequential synthesis of fused and non-fused poly-substituted dihydropyridine derivatives under catalyst-free conditions 在无催化剂条件下一步法连续合成融合和非融合多取代二氢吡啶衍生物

IF 2.1 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron

Pub Date : 2024-09-18 DOI: 10.1016/j.tet.2024.134279

Fatemeh Asilpour, Dariush Saberi, Alireza Hasaninejad

A one-pot, sequential, three-component procedure is reported for the synthesis of poly-substituted dihydropyridines via the condensation reaction of diamines or aminophenoles, 1,1-bismethylmethio-2-nitroethylene and α,β-unsaturated aromatic ketones in acetonitrile under reflux conditions. A range of fused and non-fused poly-substituted dihydropyridines were prepared in good to high yields with short reaction times.

报告采用了一种单锅、连续、三组分的方法，通过二胺或氨基苯酚、1,1-二甲基-2-硝基乙烯和 α,β-不饱和芳香酮在乙腈中的缩合反应，在回流条件下合成多取代二氢吡啶。在较短的反应时间内，制备出了一系列融合和非融合的多取代二氢吡啶，收率高。

引用次数: 0

Pd0 catalyst/carboxylic acid-mediated hydrofunctionalization of alkynes and allenes, two plausible hydropalladation mechanisms of a versatile process Pd0 催化剂/羧酸介导的炔烃和烯烃的加氢官能化--一种多功能工艺的两种似是而非的加氢钯化机制

IF 2.1 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron

Pub Date : 2024-09-18 DOI: 10.1016/j.tet.2024.134256

Jacques Muzart

The review is focused on C–C and C–heteroatom bond forming methodologies involving reactions arising after hydropalladation of alkynes and allenes using Pd⁰ catalysts associated to catalytic or stoichiometric amounts of carboxylic acids. Most of the procedures occur with complete or high atom-economy, avoiding large generation of waste and producing functionalized compounds. The synthetic scope is presented and mechanistic problems are discussed.

本综述侧重于 C-C 和 C- 异原子键形成方法，涉及使用与催化或等量羧酸有关的钯催化剂对炔烃和烯烃进行加氢钯化后产生的反应。大多数过程都具有完全或高度的原子经济性，避免了大量废物的产生，并产生了功能化化合物。本文介绍了合成范围，并讨论了机制问题。

引用次数: 0

Structural simplification of Osimertinib to elaborate new indolyle-pyrimidine-5-carbonitrile derivatives with Anti-proliferative and Anti-SARS-CoV-2 activities assisted by molecular dynamic simulation 在分子动力学模拟的辅助下，简化奥希替尼的结构，开发出具有抗增殖和抗SARS-CoV-2活性的新型吲哚基嘧啶-5-甲腈衍生物

IF 2.1 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron

Pub Date : 2024-09-18 DOI: 10.1016/j.tet.2024.134272

Safaa I. Elewa , Ibrahim F. Nassar , Ahmed F. El-Farargy , Yaseen A.M.M. Elshaier , Omnia Kutkat , Asmaa M. Elfiky , Ahmed A. El-Rashedy , Eman Mansour

Based on the simplicity and modification of the medication osimertinib, two new series of indolyle-pyrimidine-5-carbonitrile scaffolds were created and synthesized with dual action as anti-SARS-Cov-2 and anticancer. The newly created heterocyclic compounds' chemical structures were effectively characterized. With IC50 values of 18.52, 20.89, and 19.85, respectively, compounds 9b, 10, and 15 had inhibitory actions against SARS-CoV-2 when compared to remdesivir and chloroquine, which served as pharmacological controls and had IC50 values of 3.38 μM and 24.9 μM, respectively.

Furthermore, compounds 9a and 13 showed anti-proliferative activity against HepG2 cell lines with IC_50s of 5.63 μM and 3.06 μM, respectively, in comparison to doxorubicin's IC₅₀ of 7.4 μM. qRT-PCR revealed that HepG2 cells treated with compounds 9a and 13 showed increased p53 expression levels and decreased CDK1 and PI3K expression levels in comparison to doxorubicin. Molecular dynamics simulations of 20 ns duration were performed with PI3Kα, PI3Kγ, and CDK and active compound complexes. The results confirm that compound 13 has the potential to be a therapeutic candidate for additional preclinical and clinical research, as indicated by the molecular docking data.

基于对药物奥希替尼的简化和改良，我们创造并合成了两个新系列的吲哚基嘧啶-5-甲腈支架，它们具有抗SARS-Cov-2和抗癌的双重作用。新合成的杂环化合物的化学结构得到了有效表征。化合物 9b、10 和 15 对 SARS-CoV-2 的 IC50 值分别为 18.52、20.89 和 19.85，而作为药理对照的雷米西韦和氯喹的 IC50 值分别为 3.38 μM 和 24.9 μM。此外，化合物 9a 和 13 对 HepG2 细胞株具有抗增殖活性，其 IC50 值分别为 5.63 μM 和 3.06 μM，而多柔比星的 IC50 值为 7.4 μM。qRT-PCR 显示，与多柔比星相比，用化合物 9a 和 13 处理的 HepG2 细胞显示 p53 表达水平升高，CDK1 和 PI3K 表达水平降低。对 PI3Kα、PI3Kγ、CDK 和活性化合物复合物进行了持续 20 ns 的分子动力学模拟。结果证实，如分子对接数据所示，化合物 13 有可能成为临床前和临床研究的候选治疗药物。

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