几种查尔酮吡啶衍生物的合成

查尔酮是一类具有生物活性的天然产物,是黄酮类化合物重要组成部分。自然界中也存在着大量吡啶衍生物,吡啶环结构也是许多天然产物的重要结构单元。以2-乙酰基吡啶和取代的芳香醛为原料,在碱存在下,通过Clasien-Schmit反应,合成了7种不同的查尔酮吡啶衍生物。优化了合成条件,并对这些查尔酮进行了1H NMR、13CNMR、ESI-MS表征。所用方法绿色高效且具有较高的实用性,为该类化合物的大量制备提供了可行的合成策略。     

大连化物所催化杂环合成研究取得新进展

(本刊讯)中科院大连化学物理研究所在铁催化[2+2+2]环加成反应合成吡啶化合物的研究中取得新进展,相关结果以通讯的形式发表在最近一期的《德国应用化学》上(Angew.Chem.Int.Ed.2011,50,7162-7166)。吡啶及其衍生物被广泛用作有机合成试剂或作为医药、农药的生产中间体。环加成反应构建吡啶化合物原子利用率高达100%,是构建吡啶单元最直接、最高效的方法。尽管科学界在这一领域里付出了长期的努力并开发出了诸如Co、Rh、Ru、Ni、Ti等金属催化体系,但从1876年至今,该领域     

乙醛深加工制吡啶系列产品概述

吡啶系列产品主要是指吡啶及其衍生物,吡啶衍生物又称吡啶碱(Pyridine bases)。吡啶是含一个氮原子的六元芳杂环。其衍生物主要是在其环上带上各种取代基形成的一系列化合物。其中应用价值较大的是吡啶及吡啶碱。它们是:     

四苯基乙烯衍生物光物理和光化学研究

设计合成了一个四苯基乙烯衍生物Model-TPE,该化合物具有典型的聚集诱导发光(AIE)特性。1 HNMR、质谱以及高效液相色谱研究表明,有氧条件下Model-TPE经紫外光照射发生关环反应,生成二苯基取代菲衍生物,取代和未取代苯环侧关环反应得到异构体产物,提出了光氧化关环反应机理。本工作对TPE衍生物在发光及传感领域的应用有一定的指导意义。     

新型吡啶基聚氨酯脲弹性体的热机械性能与介电性能

正吡啶及其衍生物是生物体系中重要的杂环化合物,是维生素B或植物中产生的生物碱中的结构元素。吡啶衍生物可用于农业、医药和其他行业。吡啶在六元芳环上具有氮杂环结构,其衍生物在杂环化学领域具有重要作用。许多天然产物中都发现有吡啶衍生物,但对于聚合物化学来说,则是通过不同方法合成了许多具有吡啶部分的化合物。基于吡啶的性质,对刚性吡啶杂环及其衍生物掺入聚合物基质进行了研究。吡啶环可以改善热稳定性和化学稳定性,保持高温下的机械性能,并改善电学和介电性能。因此获得了新型可     

氯沙坦的合成工艺研究进展

氯沙坦为口服非肽类血管紧张素Ⅱ受体拮抗剂,于1994年首次在瑞典上市,2004年获得美国食品与药物管理局(FDA)批准,近年来一直是临床治疗高血压的一线药物。氯沙坦由咪唑环片断(A)、苯环片断(B)和(C)以及四氮唑环片断(D)拼合而成。该文根据各片断的连接次序不同,将氯沙坦的合成策略分为以下5种:"(B+C)+D+A"策略,"(B+C)+A+D"策略,"(C+D)+B+A"策略,"(C+D)+(A+B)策略"和"(A+B)+C+D"策略。并以该5种策略为主线综述了氯沙坦自诞生至今的合成工艺研究进展。     

新型含取代吡啶环的脱氢枞酸衍生物的合成和抗病毒活性研究

以脱氢枞酸为原料,依次通过酯化反应、乙酰化反应和四组分串联反应合成了11个新型含吡啶环的脱氢枞酸衍生物(化合物4a~4k)。利用FT-IR、1HNMR和ESI-MS对上述化合物进行了结构表征。采用四甲基偶氮唑蓝比色法(MTT比色法)测试了上述化合物对人体单纯疱疹病毒I型(HSV-1)的体外抗病毒活性。结果表明,该系列衍生物具有一定的抗病毒活性,对HSV-1的半数有效浓度EC50在10~25μmol/m L之间,化合物4g的抗病毒活性最强,其EC50为12.1μmol/m L。初步构效关系分析表明,将吡啶环结构引入到脱氢枞酸骨架中可以提高衍生物的抗病毒活性。     

文摘选录

张帆樊祺泉黄仲毫,试剂通讯1980,4,1 近年来,吡啶偶氮类特殊有机试剂发展较快,人们已合成了品种繁多的该类衍生物,经在分析化学中应用的筛选,找出了几个比较理想的化合物作为光度分析显色剂或络合滴定剂,其中以在吡啶环上引入卤素的衍生物为最优越。作者注意到二溴代衍生物由于在吡啶环上存在较强的负电性取代基,它会降低吡啶环碱件,使试剂的吸收光谱移向长波区域,可望在更低的pH条件下和某些金属离子反应。     

醛-酮催化氨化合成吡啶及其烷基衍生物研究进展

醛-酮催化氨化合成吡啶及其烷基衍生物(俗称吡啶碱)是工业生产吡啶类化合物的主要方法。对醛-酮催化氨化合成吡啶碱的反应机理、催化剂的进展进行了介绍,阐述了无定形硅铝酸盐作为催化剂合成吡啶碱选择性和寿命低的原因,以金属对无定形硅铝酸盐或择形硅铝酸盐分子筛进行修饰可改进催化剂的催化性能。择形硅铝酸盐分子筛的酸性对吡啶类产物的分布有显著影响,改变分子筛的硅铝比,可以调节催化剂的酸性,从而提高生成吡啶碱的选择性。     

2，6-二（2’-芳基-3’-N-乙酰基-1’，3’，4’-噁二唑啉基）吡啶的合成与表征

2,6-吡啶二甲酸经酯化、肼解首先合成2,6-吡啶二酰肼,再跟芳香醛缩合得到酰腙,进而用乙酸酐脱水闭环,合成7个含吡啶环的双噁二唑啉衍生物,其结构用1HNMR、FT-IR、MS进行了验证并对其波谱学特征予以讨论.     

单萜吲哚生物碱士的宁的合成研究进展

士的宁属于单萜吲哚生物碱,是中药马钱子的主要有效成分,具有复杂的化学结构,包含7个环系和6个手性中心。Woodward经典合成代表了有机合成领域的里程碑。经过半个多世纪的努力已有十几个科研小组以不同策略对士的宁分子进行全合成,丰富和发展了有机合成工艺。士的宁是试验新反应和新合成策略的重要目标。按照成环方式对单萜吲哚生物碱士的宁的多种合成途径进行了总结,以促进相关研究。     

A new route to 4-, 5-, and 6-indolecarboxylic acids

There are many indole derivatives bearing carboxyl or methoxycarbonyl groups on the benzene ring and these often have patent physiological activities. Synthesis of these compounds usually starts from indoles having a halogen group at the desired position on an indole ring. We now report a facile synthesis of 4-, 5-, and 6-indolecarboxylic acids from 2-bromoaniline derivatives ( 1 ). The synthetic route is shown in Figure 1.     

Synthesis of 3-Amino-4-substituted Monocyclic ß-Lactams—Important Structural Motifs in Medicinal Chemistry

Monocyclic ß-lactams (azetidin-2-ones) exhibit a wide range of biological activities, the most important of which are antibacterial, anticancer, and cholesterol absorption inhibitory activities. The synthesis of decorated monocyclic ß-lactams is challenging because their ring is highly constrained and consequently reactive, which is also an important determinant of their biological activity. We present the optimized synthesis of orthogonally protected 3-amino-4-substituted monocyclic ß-lactams. Among several possible synthetic approaches, Staudinger cycloaddition proved to be the most promising method for initial ring formation, yielding monocyclic ß-lactams with different substituents at the C-4 position, a phthalimido-protected 3-amino group, and a (dimethoxy)benzyl protected ring nitrogen. Challenging deprotection methods were then investigated. Oxidative cleavage with cerium ammonium nitrate and ammonia-free Birch reduction was found to be most effective for selective removal of ring nitrogen protection. Hydrazine hydrate was used for deprotection of the phthalimido group, and the procedure had to be modified by the addition of HCl in the case of aromatic substituents at the C-4 position. The presented methods and the synthesized 3-amino-4-substituted monocyclic ß-lactam derivatives are an important step toward new ß-lactams with potential pharmacological activities.     

The Anticancer Drug Ellipticine Activated with Cytochrome P450 Mediates DNA Damage Determining Its Pharmacological Efficiencies: Studies with Rats,Hepatic Cytochrome P450 Reductase Null (HRN?) Mice and Pure Enzymes

Ellipticine is a DNA-damaging agent acting as a prodrug whose pharmacological efficiencies and genotoxic side effects are dictated by activation with cytochrome P450 (CYP). Over the last decade we have gained extensive experience in using pure enzymes and various animal models that helped to identify CYPs metabolizing ellipticine. In this review we focus on comparison between the in vitro and in vivo studies and show a necessity of both approaches to obtain valid information on CYP enzymes contributing to ellipticine metabolism. Discrepancies were found between the CYP enzymes activating ellipticine to 13-hydroxy- and 12-hydroxyellipticine generating covalent DNA adducts and those detoxifying this drug to 9-hydroxy- and 7-hydroellipticine in vitro and in vivo. In vivo, formation of ellipticine-DNA adducts is dependent not only on expression levels of CYP3A, catalyzing ellipticine activation in vitro, but also on those of CYP1A that oxidize ellipticine in vitro mainly to the detoxification products. The finding showing that cytochrome b₅ alters the ratio of ellipticine metabolites generated by CYP1A1/2 and 3A4 explained this paradox. Whereas the detoxification of ellipticine by CYP1A and 3A is either decreased or not changed by cytochrome b₅, activation leading to ellipticine-DNA adducts increased considerably. We show that (I) the pharmacological effects of ellipticine mediated by covalent ellipticine-derived DNA adducts are dictated by expression levels of CYP1A, 3A and cytochrome b₅, and its own potency to induce these enzymes in tumor tissues, (II) animal models, where levels of CYPs are either knocked out or induced are appropriate to identify CYPs metabolizing ellipticine in vivo, and (III) extrapolation from in vitro data to the situation in vivo is not always possible, confirming the need for these animal models.     

Lysosomal Exocytosis of Olivacine on the Way to Explain Drug Resistance in Cancer Cells

Ellipticine is an indole alkaloid with proven antitumor activity against various tumors in vitro and a diverse mechanism of action, which includes topoisomerase II inhibition, intercalation, and cell cycle impact. Olivacine—ellipticine’s isomer—shows similar properties. The objectives of this work were as follows: (a) to find a new path of olivacine synthesis, (b) to study the cytotoxic properties of olivacine and ellipticine in comparison to doxorubicin as well as their impact on the cell cycle, and (c) to investigate the cellular pharmacokinetics of the tested compounds to understand drug resistance in cancer cells better. SRB and MTT assays were used to study the anticancer activity of olivacine and ellipticine in vitro. Both compounds showed a cytotoxic effect on various cell lines, most notably on the doxorubicin-resistant LoVo/DX model, with olivacine’s cytotoxicity approximately three times higher than doxorubicin. Olivacine proved to be less effective against cancer cells and less cytotoxic to normal cells than ellipticine. Olivacine proved to have fluorescent properties. Microscopic observation of cells treated with olivacine showed the difference in sensitivity depending on the cell line, with A549 cells visibly affected by a much lower concentration of olivacine than normal NHDF cells. An increased percentage of cells in G0/G1 was observed after treatment with olivacine and ellipticine, suggesting an impact on cell cycle progression, potentially via higher p53 protein expression, which blocks the transition from G0/G1 to the S phase. Ellipticine induced apoptosis at a concentration as low as 1 μM. It has been proved that the tested compounds (ellipticine and olivacine) undergo lysosomal exocytosis. Reducing exocytosis is possible through the use of compounds that inhibit the activity of the proton pump. Olivacine and ellipticine exhibited diverse cytotoxicity against a panel of cancer cells. Analysis of the lysosomal exocytosis of olivacine and ellipticine shows the need to look for derivatives with comparable anticancer activity but reduced weak base character.     

Stereocontrolled Synthesis of Spiroketals: An Engine for Chemical and Biological Discovery

Spiroketals are key structural motifs found in diverse natural products with compelling biological activities. However, stereocontrolled synthetic access to spiroketals, independent of their inherent thermodynamic preferences, is a classical challenge in organic synthesis that has limited in-depth biological exploration of this intriguing class. Herein, we review our laboratory's efforts to advance the glycal epoxide approach to the stereocontrolled synthesis of spiroketals via kinetically controlled spirocyclization reactions. This work has provided new synthetic methodologies with applications in both diversity- and target-oriented synthesis, fundamental insights into structure and reactivity, and efficient access to spiroketal libraries and natural products for biological evaluation.     

Four-membered Heterocyclic Rings from Iminophosphoranes. Preparation and reactivity of 2,4-diimino-1,3-diazetidines and related compounds

Aza Wittig-type reaction either of iminophosphoranes derived from N-aminoheterocycles or bis(iminophosphoranes) has been found to be an useful method for the synthesis of the four-membered ring 1,3-diazetidine. This account deals with the following cyclization reaction, reactivity and synthetic utility of this ring system and related compounds.     

Paraherquamides,brevianamides, and asperparalines: laboratory synthesis and biosynthesis. An interim report

Studies from our laboratories on the paraherquamide, brevianamide, and asperparaline families of natural products are reviewed. It has been proposed that the unique core ring system that is common to this family of compounds arises by a biological intramolecular Diels-Alder cycloaddition reaction. Key biosynthetic studies are described, along with classical synthetic approaches as well as those inspired by Nature for the synthesis of these interesting molecules.     

聚乳酸高效催化剂的研究进展

聚乳酸作为一种生物可降解塑料,具有绿色环保、原料来源广泛等优点,近年来对于聚乳酸的合成和应用研究越来越多。聚乳酸的合成方法可分为直接法和间接法(丙交酯的开环聚合)。在聚乳酸的合成过程中,催化剂起着非常关键的作用,不同的合成过程催化剂的选择也存在一定的差异,主要对聚乳酸的合成过程中所用到的高效催化剂进行综述。     

Total synthesis of indoline alkaloids: A cyclopropanation strategy

Indoline alkaloids constitute a large class of natural products; their diverse and complex structures contribute to potent biological activities in a range of molecules. Designing an appropriate strategy for the total synthesis of indoline alkaloids is a difficult task that depends on being able to efficiently assemble the core architectures. The best strategies allow access to a variety of different indoline alkaloid structures in a minimum of steps. The cyclopropanation of simple olefins and the subsequent synthetic transformation of the resulting cyclopropyl intermediates has been intensively studied in recent decades. In contrast, the cyclopropanation of enamines, especially for the construction of complex nitrogen-containing ring systems, remained relatively unexplored. Previous success with the cyclopropanation of simple indoles to form stable indolylcyclopropanocarboxylates encouraged us to explore the assembly of indoline alkaloid skeletons with cyclopropanation as a key reaction. Theoretically, indolylcyclopropanocarboxylates are doubly activated by a vicinally substituted amino group and carboxyl group; that is, they are typical donor-acceptor cyclopropanes. Accordingly, they tend to yield an active iminium intermediate, which can undergo inter- and intramolecular nucleophilic reactions to form the core structure of indoline alkaloids with an expanded ring system. In this Account, we summarize our efforts to develop a cascade or stepwise reaction of cyclopropanation/ring-opening/iminium cyclization (the CRI reaction) on tryptamine derivatives for assembling indoline alkaloid skeletons. With the CRI approach, three types of indoline alkaloid skeletons have been efficiently constructed: (i) hexahydropyrrolo[2,3-b]indoline (type I), (ii) tetrahydro-9a,4a-iminoethano-9H-carbazole (type II), and (iii) tetrahydroquinolino[2,3-b]indoline (type III). The effects of substituents on tryptamine derivatives were carefully investigated for inter- and intramolecular CRI reactions during construction of type I and type II skeletons. These results provided a basis for the further design and synthesis of complex natural products containing nitrogen. The usefulness of the CRI reaction is well demonstrated by our total synthesis of structurally intriguing indoline alkaloids such as N-acetylardeemin, minfiensine, vincorine, and communesin F. In addition, we highlight advances by other groups in construction of the three types of skeletons as well as their total syntheses of these indoline alkaloids. Discussion of the total syntheses of these indoline alkaloids focuses on comparing the individual synthetic strategies for forming the ring systems embedded in the final products. We also describe the total synthesis of perophoramidine, which has the same type III skeleton as communesin F. The observation of a retro Diels-Alder reaction during our synthesis of communesin F inspired the hetero Diels-Alder reaction on which our total synthesis of perophoramidine was based.