含连续全碳季碳手性中心天然产物的全合成研究进展

连续全碳季碳手性中心是活性天然产物中常见且具有合成挑战性的结构单元.本文首先介绍了本研究组在含连续全碳季碳手性中心天然产物的全合成研究进展;随后对含多个(≥3)连续全碳季碳手性中心天然产物的合成策略进行分类;最后以Waihoensene和Crinipellins家族天然产物的全合成研究为例,结合其他课题组报道的全合成研究,对比分析相关合成方法学及合成策略的优势和不足.     

由D-木糖衍生的实用手性合成砌块

本文报道了以价廉易得的D-木糖为起始原料合成数种尚未见报道过的含有潜在1,3-二羟基手性及末端环氧的光学活性合成砌块的简便实用方法。     

樟脑衍生的β-羟基酮的不对称合成

不对称合成方法学及其应用是现代合成化学的基石之一,也是当代有机化学及其相关学科研究的热点和前沿。在不对称合成越来越重要的今天,手性试剂的作用已是最为重要和必不可少的反应试剂。价廉易得的天然樟脑作为天然手性源,在不对称合成领域中一直备受关注[1,2,3,4],其可用于合     

亚胺及其类似物的催化不对称炔基化反应新进展

手性炔丙胺是天然产物和药物活性分子不对称全合成中常用的关键中间体,亚胺及其类似物的不对称炔基化反应可以为该砌块提供高效高对映选择性的合成路径;此外通过合理的底物和反应设计,亚胺的不对称炔基化反应还能作为一系列串联反应的起点,来合成多种结构新颖的含氮杂环化合物.因此,亚胺及其类似物的高效高对映选择性炔基化反应得到合成化学...     

D-奎尼酸: 一个多用途的手性合成子

综述了D-奎尼酸在各种环状和链状生物活性化合物合成中的应用。奎尼酸分子中特有的顺式γ-羟基羧酸的结构单元提供了区别分子中各种羟基,以及进行其它区域选择性和立体选择性控制的方便途径。奎尼酸的结构特征以及其价廉、易得的优点,使之成为一个有用的而且重要的手性合成子。     

推-拉电子体系环丙烷的不对称合成及其对映选择性开环/环化反应研究进展

含有推-拉电子(DA)体系的张力环化合物,例如DA环丙烷,是非常有用的合成砌块,被应用于天然产物全合成以及合成具有生物活性的分子的研究中。 近年来,本课题组利用手性铜、镍等配合物为催化剂,一方面发展了一系列高效合成手性DA环丙烷的新方法;另一方面陆续实现了仲胺、醇、硝酮、氮杂亚胺叶立德、烯醇硅醚、吲哚等多种亲核试剂与DA环丙烷的高对映选择性开环/环化反应。 本文结合我们课题组工作综述了DA环丙烷化合物的不对称合成、开环/环化反应以及动力学拆分方面的主要研究进展并进行了展望。     

(—)-Isochaetominine推测结构的对映选择性全合成与结构修正

报道生物碱isochaetominine推测结构8的对映选择性全合成与结构修正.采用立体多样性合成策略,通过L-色氨酸与L-丙氨酸苄酯组合,以DMDO氧化启动的串联反应为关键反应,经5步高效地完成了isochaetominine推测结构8及其立体异构体(+)-2,3,14-tri-epi-chaetominine(12)的全合成.基于本实验室此前有关毛壳菌素(1)立体多样性合成的工作,天然isochaetominine的结构修正为(-)-11-epi-chaetominine(18).我们此前已完成了该天然产物的首次对映选择性全合成(从L-色氨酸出发,5步,总产率31.6%).此外,通过研究色氨酸与缬氨酸叔丁酯组合,建立了isochaetominine C三个非对映立体异构体的立体多样性合成.最后,证实了化合物13B无法进行C(14)位定点差向异构化,但可以进行C(11)和C(14)双差向异构化.     

醛,酮,醇和胺的不对称合成

根据对866个有代表性的旋光物质的研究,H.J.Roth和A.Kleemann指出,半数以上的旋光物质是手性的,至少具有一个或一个以上手性中心。其中22％光活性物质来自天然产物或从天然产物通过部分合成得到。78％光活性物质是全合成的,但是纯的对映体仅占5％。众所周知,光学活性物质的对映体     

过渡金属催化的有机硼试剂对亚胺的不对称加成研究进展

手性胺是有机合成中一类非常重要的合成砌块,在天然产物、生物活性分子及药物分子中广泛存在,因此发展高效的构建手性胺类化合物的方法,一直都是合成有机化学家们关注的重点.有机硼试剂近年来以其低毒、稳定、易得等优点逐渐受到合成化学家的青睐,被越来越多地用于过渡金属催化的反应中.本文综述了近十多年来基于手性辅剂及手性催化策略的过渡金属催化的有机硼试剂对亚胺的不对称加成研究进展,着重探讨了各种手性配体在反应中的应用以及α-手性胺类化合物的立体选择性构建.     

高效催化不对称还原潜手性二酮及产物在合成1，5－二苯基吡咯烷和1，5－二苯基噻吩烷中的应用

本文报道了一种高效不对称催化还原潜手性二酮的方法，该方法使用的是简便易得的NaBH₄和路易斯酸SnCl₂现场产生硼烷，以天然的L-脯氨酸经过简单的转化所得的 (S)-(-)-α, α-二苯基-吡咯烷甲醇作为手性催化剂，该方法对大部分二酮的还原都非常有效，尤其是对1，4 二酮及1，5 二酮的还原，可以得到极好的非对映选择性和对映选择性（up to>99% e e）。还原所得的手性二醇本身是非常有效的手性催化剂同时可以转化成其它有意义的手性催化剂和辅基，而且许多天然产物中都含有手性二醇的结构单元。本文还报道了由光学活性的1，4二醇合成的1，5－二苯基吡咯烷和1，5－二苯基噻吩烷的方法，这两类化合物都是不对称合成中应用广泛的手性催化剂。     

Mechanochemistry in Portugal—A Step towards Sustainable Chemical Synthesis

In Portugal, publications with mechanochemical methods date back to 2009, with the report on mechanochemical strategies for the synthesis of metallopharmaceuticals. Since then, mechanochemical applications have grown in Portugal, spanning several fields, mainly crystal engineering and supramolecular chemistry, catalysis, and organic and inorganic chemistry. The area with the most increased development is the synthesis of multicomponent crystal forms, with several groups synthesizing solvates, salts, and cocrystals in which the main objective was to improve physical properties of the active pharmaceutical ingredients. Recently, non-crystalline materials, such as ionic liquids and amorphous solid dispersions, have also been studied using mechanochemical methods. An area that is in expansion is the use of mechanochemical synthesis of bioinspired metal-organic frameworks with an emphasis in antibiotic coordination frameworks. The use of mechanochemistry for catalysis and organic and inorganic synthesis has also grown due to the synthetic advantages, ease of synthesis, scalability, sustainability, and, in the majority of cases, the superior properties of the synthesized materials. It can be easily concluded that mechanochemistry is expanding in Portugal in diverse research areas.     

过渡金属催化的1,2,3-三氮唑导向的C—H键官能团化反应研究进展

1,2,3-三氮唑化合物是一类具有重要生理活性的含氮杂环化合物, 其在医药、农药、材料科学等领域都具有广泛的应用. 不断开发基于三氮唑骨架的新型结构, 寻找新型高效的合成三氮唑衍生物的方法具有重要的意义和应用价值. 过渡金属催化的C—H键活化策略具有操作简便、效率高、三废少等优点, 是现代有机合成中高效构筑C—C键和C—X键的强大工具. 近年来, 过渡金属催化的三氮唑导向的C—H官能团化反应受到科学工作者的广泛关注, 该方法以不同结构的1,2,3-三氮唑作为导向基团, 在不同反应条件下通过直接活化C—H键来构建新的C—C键和C—X键, 高效合成复杂的三氮唑衍生物. 综述了近年来1,2,3-三氮唑导向下过渡金属催化的C—H键官能团化反应研究进展, 按照成键类型(碳-碳键、碳-杂键以及环化反应)对这些反应进行了梳理和总结, 并对今后该领域的发展进行了展望.     

Toward a Greener World—Cyclodextrin Derivatization by Mechanochemistry

Cyclodextrin (CD) derivatives are a challenge, mainly due to solubility problems. In many cases, the synthesis of CD derivatives requires high-boiling solvents, whereas the product isolation from the aqueous methods often requires energy-intensive processes. Complex formation faces similar challenges in that it involves interacting materials with conflicting properties. However, many authors also refer to the formation of non-covalent bonds, such as the formation of inclusion complexes or metal–organic networks, as reactions or synthesis, which makes it difficult to classify the technical papers. In many cases, the solubility of both the starting material and the product in the same solvent differs significantly. The sweetest point of mechanochemistry is the reduced demand or complete elimination of solvents from the synthesis. The lack of solvents can make syntheses more economical and greener. The limited molecular movements in solid-state allow the preparation of CD derivatives, which are difficult to produce under solvent reaction conditions. A mechanochemical reaction generally has a higher reagent utilization rate. When the reaction yields a good guest co-product, solvent-free conditions can be slower than in solution conditions. Regioselective syntheses of per-6-amino and alkylthio-CD derivatives or insoluble cyclodextrin polymers and nanosponges are good examples of what a greener technology can offer through solvent-free reaction conditions. In the case of thiolated CD derivatives, the absence of solvents results in significant suppression of the thiol group oxidation, too. The insoluble polymer synthesis is also more efficient when using the same molar ratio of the reagents as the solution reaction. Solid reactants not only reduce the chance of hydrolysis of multifunctional reactants or side reactions, but the spatial proximity of macrocycles also reduces the length of the spacing formed by the crosslinker. The structure of insoluble polymers of the mechanochemical reactions generally is more compact, with fewer and shorter hydrophilic arms than the products of the solution reactions.     

Substituted Pyrazoles and Their Heteroannulated Analogs—Recent Syntheses and Biological Activities

Pyrazoles are considered privileged scaffolds in medicinal chemistry. Previous reviews have discussed the importance of pyrazoles and their biological activities; however, few have dealt with the chemistry and the biology of heteroannulated derivatives. Therefore, we focused our attention on recent topics, up until 2020, for the synthesis of pyrazoles, their heteroannulated derivatives, and their applications as biologically active moieties. Moreover, we focused on traditional procedures used in the synthesis of pyrazoles.     

Distigmasterol-Modified Acylglycerols as New Structured Lipids—Synthesis,Identification and Cytotoxicity

Plant sterols, also referred as phytosterols, have been known as bioactive compounds which have cholesterol-lowering properties in human blood. It has been established that a diet rich in plant sterols or their esters alleviates cardiovascular diseases (CVD), and also may inhibit breast, colon and lung carcinogenesis. Phytosterols, in their free and esterified forms, are prone to thermo-oxidative degradation, where time and temperature affect the level of degradation. Looking for new derivatives of phytosterols with high thermo-oxidative stability for application in foods, our idea was to obtain novel structured acylglycerols in which two fatty acid parts are replaced by stigmasterol residues. In this work, asymmetric (1,2- and 2,3-) distigmasterol-modified acylglycerols (dStigMAs) were synthesized by the covalent attachment of stigmasterol residues to sn-1 and sn-2 or sn-2 and sn-3 positions of 3-palmitoyl-sn-glycerol or 1-oleoyl-sn-glycerol, respectively, using a succinate or carbonate linker. The chemical structures of the synthesized compounds were identified by NMR, HR-MS, and IR data. Moreover, the cytotoxicity of the obtained compounds was determined. The dStigMAs possessing a carbonate linker showed potent cytotoxicity to cells isolated from the small intestine and colon epithelium and liver, whereas the opposite results were obtained for compounds containing a succinate linker.     

Photochemical Synthesis of Gold and Silver Nanoparticles—A Review

Nanomaterials have supported important technological advances due to their unique properties and their applicability in various fields, such as biomedicine, catalysis, environment, energy, and electronics. This has triggered a tremendous increase in their demand. In turn, materials scientists have sought facile methods to produce nanomaterials of desired features, i.e., morphology, composition, colloidal stability, and surface chemistry, as these determine the targeted application. The advent of photoprocesses has enabled the easy, fast, scalable, and cost- and energy-effective production of metallic nanoparticles of controlled properties without the use of harmful reagents or sophisticated equipment. Herein, we overview the synthesis of gold and silver nanoparticles via photochemical routes. We extensively discuss the effect of varying the experimental parameters, such as the pH, exposure time, and source of irradiation, the use or not of reductants and surfactants, reagents’ nature and concentration, on the outcomes of these noble nanoparticles, namely, their size, shape, and colloidal stability. The hypothetical mechanisms that govern these green processes are discussed whenever available. Finally, we mention their applications and insights for future developments.     

N-Phenacyldibromobenzimidazoles—Synthesis Optimization and Evaluation of Their Cytotoxic Activity

Antifungal N-phenacyl derivatives of 4,6- and 5,6-dibromobenzimidazoles are interesting substrates in the synthesis of new antimycotics. Unfortunately, their application is limited by the low synthesis yields and time-consuming separation procedure. In this paper, we present the optimization of the synthesis conditions and purification methods of N-phenacyldibromobenzimidazoles. The reactions were carried out in various base solvent-systems including K₂CO₃, NaH, KOH, t-BuOK, MeONa, NaHCO₃, Et₃N, Cs₂CO₃, DBU, DIPEA, or DABCO as a base, and MeCN, DMF, THF, DMSO, or dioxane as a solvent. The progress of the reaction was monitored using HPLC analysis. The best results were reached when the reactions were carried out in an NaHCO₃–MeCN system at reflux for 24 h. Additionally, the cytotoxic activity of the synthesized compounds against MCF-7 (breast adenocarcinoma), A-549 (lung adenocarcinoma), CCRF-CEM (acute lymphoblastic leukemia), and MRC-5 (normal lung fibroblasts) was evaluated. We observed that the studied cell lines differed in sensitivity to the tested compounds with MCF-7 cells being the most sensitive, while A-549 cells were the least sensitive. Moreover, the cytotoxicity of the tested derivatives towards CCRF-CEM cells increased with the number of chlorine or fluorine substituents. Furthermore, some of the active compounds, i.e., 2-(5,6-dibromo-1H-benzimidazol-1-yl)-1-(3,4-dichlorophenyl)ethanone (4f), 2-(4,6-dibromo-1H-benzimidazol-1-yl)-1-(2,4,6-trichlorophenyl)ethanone (5g), and 2-(4,6-dibromo-1H-benzimidazol-1-yl)-1-(2,4,6-trifluorophenyl)ethanone (5j) demonstrated pro-apoptotic properties against leukemic cells with derivative 5g being the most effective.     

条件下C—O—P键的形成

利用水热反应模拟原始地球的水热环境, 以甘油和磷酸二氢铵为原料, 采用非生物手段合成了sn-甘油-1(3)-磷酸和甘油-2-磷酸2种磷酸酯类物质. 通过此反应, 无机磷进入生物分子形成了在生物体中起重要作用C—O—P键. 研究了反应温度、 反应时间及矿物催化剂对反应的影响. 在蒙脱土的催化下, C—O—P键的产率最大可达到1.15%(摩尔分数).     

Thymodepressin—Unforeseen Immunosuppressor

The paper summarizes the available information concerning the biological properties and biomedical applications of Thymodepressin. This synthetic peptide drug displays pronounced immunoinhibitory activity across a wide range of conditions in vitro and in vivo. The history of its unforeseen discovery is briefly reviewed, and the current as well as potential expansion areas of medicinal practice are outlined. Additional experimental evidence is obtained, demonstrating several potential advantages of Thymodepressin over another actively used immunosuppressor drug, cyclosporin A.     

pyAIR—A New Software Tool for Breathomics Applications—Searching for Markers in TD-GC-HRMS Analysis

Volatile metabolites in exhaled air have promising potential as diagnostic biomarkers. However, the combination of low mass, similar chemical composition, and low concentrations introduces the challenge of sorting the data to identify markers of value. In this paper, we report the development of pyAIR, a software tool for searching for volatile organic compounds (VOCs) markers in multi-group datasets, tailored for Thermal-Desorption Gas-Chromatography High Resolution Mass-Spectrometry (TD-GC-HRMS) output. pyAIR aligns the compounds between samples by spectral similarity coupled with retention times (RT), and statistically compares the groups for compounds that differ by intensity. This workflow was successfully tested and evaluated on gaseous samples spiked with 27 model VOCs at six concentrations, divided into three groups, down to 0.3 nL/L. All analytes were correctly detected and aligned. More than 80% were found to be significant markers with a p-value < 0.05; several were classified as possibly significant markers (p-value < 0.1), while a few were removed due to background level. In all group comparisons, low rates of false markers were found. These results showed the potential of pyAIR in the field of trace-level breathomics, with the capability to differentially examine several groups, such as stages of illness.