多环型Xanthone类天然产物的合成研究进展

多环型xanthone类天然产物是一类具有高度氧化态和六环骨架结构的天然产物.目前分离得到的此类化合物主要来源于放线菌.由于这类化合物具有结构特独、广泛的抗细菌活性、一定程度的抗真菌活性以及良好的抗肿瘤活性,吸引了大量有机合成和药物化学等领域学者的关注.近十年来,相关的生物和化学合成以及药物化学研究报道明显增多,主要总结了多环型xanthone类天然产物的合成研究进展.     

通过环加成反应和串联反应构建桥环化合物的研究进展

桥环化合物广泛存在于天然产物和具有重要生理活性的分子中,在药物化学、天然产物化学、合成化学、材料化学及生命科学等领域具有重要的应用价值.近年来,经过广大化学工作者的不懈努力,己发展了系列高效构建桥环化合物的新方法.从环加成反应和串联反应两种策略出发,详细介绍近五年来用于构建桥环化合物的方法及最新研究进展,简要分析目前方...     

一价铑催化的1-取代乙烯基环丙烷的形式上[5+1]/[2+2+1]环加成反应:一步构建多官能团化的5/5/6三环化合物

自然界中高生物活性的天然产物一般都以多环化合物作为它的骨架或者骨架组成单元.因此,对于现代有机合成化学来说,要高效地合成这些天然产物和其类似物来开发新药物分子,就有必要发展高效的、普适性广的合成方法来构建多环化合物.北京大学化学与分子工程学院余志祥课题组利用一价铑催化的1-取代乙烯基环丙烷化合物与     

放线菌来源生物碱的生物合成机制

生物碱类天然产物通常具有复杂多样的化学结构和广泛的生物活性,因此备受生物学、化学、药学领域研究者的关注。微生物是仅次于植物的生物碱类天然产物重要来源,微生物尤其是放线菌产生的众多次生代谢产物中,也包括很多生物碱。对放线菌来源生物碱的骨架结构和药效基团生物合成研究,不仅能够丰富人们对天然产物结构形成原理的理解,还可以为运用合成生物学技术人工合成此类化合物提供重要的遗传元件。本文从模块化生物合成和非模块化生物合成两种方式,综述放线菌来源生物碱的生物合成基因簇、途径及其酶催化反应过程。     

(-)-Principinol C的全合成研究

<正>天然产物全合成是有机化学中的重要研究领域,其持续不断发展为创新药物的发现提供了重要的保证.其中,约一半新发现的小分子药物都来源于天然产物及其衍生物^[1].由于天然产物结构复杂,含量稀少且难以通过分离手段来获得稳定来源,极大地限制了天然产物在药物研发中的应用.合成方法与策略的创新,对推动天然产物全合成领域的发展起着非常关键的作用.值得注意的是,利用分子内的Pauson-Khand反应在合成具有环戊烯酮骨架的天然产物中扮演着重要角色^[2].     

3,4-桥环吲哚类生物碱的合成研究进展

取代的吲哚类天然产物是自然界中普遍存在的一类杂环化合物,由于其具有广泛的生理活性,以及相当一部分作为重要的临床使用药物,100多年以来,吲哚的合成及官能团化一直是有机合成化学家关注的一个重要领域.在众多吲哚类生物碱中,含有3,4-桥环吲哚骨架的天然产物占据了相当一部分,由于其独特的结构和良好的生物活性,这些分子引起了有机合成化学家的广泛兴趣.重点概述了构建3,4-桥环骨架的主要合成方法和策略,并对一些方法在天然产物全合成中的应用作简要介绍.     

光促进的山道年重排反应在复杂萜类天然产物全合成中的应用

萜类化合物在自然界中广泛存在,其中倍半萜内酯广泛存在于各种药用植物中,是许多传统中草药的主要活性成分,然而这类化合物的化学全合成却极具挑战性.山道年是一种廉价的可再生资源,且光促进的山道年重排反应是一种构建愈创木内酯骨架的高效方法,在萜类天然产物合成中得到广泛应用.就光促进的山道年重排在复杂萜类天然产物的合成工作进行简单的概述,主要包括倍半萜内酯及其寡聚物全合成以及个别二萜天然产物的骨架合成研究.     

基于天然产物骨架的有机凝胶

天然产物结构复杂,生理活性独特,常被用作先导化合物,经过结构修饰和改造,发展为具有重要药用价值的化合物,在保障人类健康方面发挥重要的作用.近年来,具有独特立体结构、多修饰位点、良好生物相容性和生物活性的天然产物作为构筑单元,已应用到基于分子自组装的有机功能材料研究领域中.介绍以天然甾体、三萜、肽、糖等为结构骨架,设计合成的功能分子在有机凝胶方面的研究现状及其潜在的应用.     

手性诱导构建磷手性中心不对称合成有机磷功能化合物研究进展

有机磷化学是有机化学和生命科学研究的重要分支,具有磷手性中心的有机磷化合物在医药、农药、材料和不对称合成等研究领域中具有广泛的应用.利用自然界广泛存在的天然手性化合物作为手性诱导试剂,通过相应的化学转化可以高效合成具有光学活性的磷手性有机磷功能化合物.综述了近年来利用薄荷醇、金雀花碱、麻黄碱和碳水化合物等天然产物作为手性诱导试剂,不对称合成磷手性有机磷功能化合物的研究进展.     

多样性导向的“类天然产物”化合物库合成

天然产物是药物发现中先导化合物的重要来源.高通量筛选技术的发展和近年来化学生物学研究的深入,对拓展天然产物与活性相关的＂化学空间＂提出了新要求.用多样性导向合成方法建立骨架多样、构造复杂、立体化学多样性的＂类天然产物＂化合物库进行生物学相关研究,并以此为基础发现药物先导化合物正在成为一种趋势.在此过程中,发展具有立体选择性和区域选择性,能够广泛应用于多种底物的有机化学反应起着关键作用.     

Dendralenes branch out: cross-conjugated oligoenes allow the rapid generation of molecular complexity

Twenty-seven years ago, H. Hopf published the only previous comprehensive review on branched oligoenes that had the title "Dendralenes: A Neglected Family of Hydrocarbons". The dendralenes are no longer neglected. Research into the synthesis, properties, and applications of dendralenes is rapidly gaining momentum and this Review summarizes important recent findings. From significant fundamental properties (the first demonstration of alternating behavior since the annulenes) through to unparalleled complexity-generating synthetic transformations, this fundamental oligoene family is coming of age. Effective synthetic approaches to cyclic and acyclic dendralene systems are analyzed and classified. The most powerful synthetic transformations of the dendralenes, diene-transmissive Diels-Alder reactions, are surveyed in detail.     

From propargylic biscarbonate to diaryl[n]dendralenes

An efficient cross-coupling reaction using a low cost carbon-supported palladium (Pd/C) catalyst for the synthesis of cross-conjugated compounds, diaryl[n]dendralenes, has been developed. The reaction of a propargylic biscarbonate with phenylboronic acid using Pd/C and phosphine ligand (S-Phos) gave 2,3-diphenyl[2]dendralene in high yield. We found that Pd/C was an effective catalyst for the synthesis of dialyl[n]dendralenes. The synthesis of various dendralenes was successfully achieved under the optimized conditions, giving dialyl [2] and [4] dendralenes in good yields.     

A Broad-Spectrum Synthesis of Tetravinylethylenes

The first general synthesis of compounds of the tetravinylethylene (TVE) family is reported. Ramirez-type dibromo-olefination of readily accessible penta-1,4-dien-3-ones generates 3,3-dibromo[3]dendralenes, which undergo twofold Negishi, Suzuki–Miyaura or Mizoroki–Heck reactions with a wide variety of olefinic coupling partners. This route delivers a broad range of unsymmetrically substituted tetravinylethylenes with up to three different alkenyl substituents attached to the central C=C bond. The extensive scope of the approach is demonstrated by the preparation of the first higher order oligo-alkenic through-conjugated/cross-conjugated hybrid compounds. An unsymmetrically substituted TVE is shown to undergo a domino electrocyclization–cycloaddition with high site-selectivity and diastereoselectivity, thereby demonstrating the substantial synthetic potential of substituted TVEs for controlled, rapid structural complexity generation.     

Multi-Step Continuous-Flow Organic Synthesis: Opportunities and Challenges

Continuous-flow multi-step synthesis takes the advantages of microchannel flow chemistry and may transform the conventional multi-step organic synthesis by using integrated synthetic systems. To realize the goal, however, innovative chemical methods and techniques are urgently required to meet the significant remaining challenges. In the past few years, by using green reactions, telescoped chemical design, and/or novel in-line separation techniques, major and rapid advancement has been made in this direction. This minireview summarizes the most recent reports (2017–2020) on continuous-flow synthesis of functional molecules. Notably, several complex active pharmaceutical ingredients (APIs) have been prepared by the continuous-flow approach. Key technologies to the successes and remaining challenges are discussed. These results exemplified the feasibility of using modern continuous-flow chemistry for complex synthetic targets, and bode well for the future development of integrated, automated artificial synthetic systems.     

Ruthenium‐Catalyzed Synthesis of 2,3‐Cyclo[3]dendralenes and Complex Polycycles from Propargyl Alcohols

Ruthenium‐catalyzed cascade transformations for the synthesis of 2,3‐cyclo[3]dendralenes and multicomponent processes based thereon to generate complex polycycles are presented. The combination of allylation–cyclization sequences with diene‐transmissive Diels–Alder reactions allows the rapid and selective construction of natural‐product‐like motifs from easily accessible starting materials in a one‐pot process and provides a new method to access potential drug candidates.     

Teaching target-oriented and diversity-oriented organic synthesis at Harvard University

Diversity-oriented synthesis presents many formidable challenges to the practitioners of synthetic organic chemistry. Those challenges include the effective teaching of this new and evolving discipline to ensure that students are well positioned to begin exploring its full potential. Fortunately, the teaching of synthetic organic chemistry has a rich history in the context of target-oriented synthesis, and this precedent can serve as a strong foundation for meeting the challenges of teaching diversity-oriented synthesis.     

Synthesis and Applications of Tricarbonyliron Complexes of Dendralenes

[3]Dendralene and [4]dendralene are converted smoothly into tricarbonyliron complexes. The structures of four complexes analyzed by DFT and single‐crystal X‐ray analysis show that, in contrast to free hydrocarbons, complexed dendralenes prefer a roughly in‐plane conformation. The complexes are stable towards Fe(CO)₃ group migration up to 150 °C. The synthetic value of Fe(CO)₃ complexation in the dendralene series is demonstrated through a variety of selective synthetic manipulations (Diels–Alder reaction, dipolar cycloaddition, Simmons–Smith cyclopropanation, dihydroxylation, olefin cross metathesis) that are not achievable by direct transformation of the free hydrocarbons. Application to the synthesis of a previously unreported, highly reactive linear/cross‐conjugated hydrocarbon is also described.     

Synthesis of classes of ternary metal oxide nanostructures

Nanoscale structures, such as nanoparticles, nanorods, nanowires, nanocubes, and nanotubes, have attracted extensive synthetic attention as a result of their novel size-dependent properties. Ideally, the net result of nanoscale synthesis is the production of structures that achieve monodispersity, stability, and crystallinity with a predictable morphology. Many of the synthetic methods used to attain these goals have been based on principles derived from semiconductor technology, solid state chemistry, and molecular inorganic cluster chemistry. We describe a number of advances that have been made in the reproducible synthesis of various ternary oxide nanomaterials, including alkaline earth metal titanates, alkali metal titanates, bismuth ferrites, ABO(4)-type oxides, as well as miscellaneous classes of ternary metal oxides.     

Ketenes in polymer-assisted synthesis

Since its inception, ketene chemistry has developed into a unique and well-established source of useful transformations for conventional synthetic organic chemistry. It is, therefore, not surprising that soon after their movement from the realm of peptide and peptoid libraries to that of small molecules, combinatorial chemists have sought the benefits of ketene chemistry to satisfy their own synthetic needs. The ability of these versatile molecules to undergo reactions with nucleophiles, and to participate in cycloadditions and cyclocondensations, has been utilized for the preparation of diverse heterocyclic compounds, and has added to the advantages of polymer-assisted synthesis for rapid purification. Different types of ketenes and different methods for their generation have been involved, which illustrates the potential diversity of the chemistry. There is now a better grasp of the effect of the fragility of these sometimes transient molecules on the reactions involving solid supports, and this augurs well for the application of some of the more recent developments in ketene chemistry to the generation of small-molecule libraries.     

有机化学进展(2011~2012)

本文综述了中国大陆地区有机化学研究人员2011至2012年两年内在合成方法学、有机合成化学、元素有机化学以及天然产物化学等领域获得的重要成果。文章中共引用参考文献355篇,其中110多篇手性金属配合物和有机小分子催化的不对称反应、金属催化的碳氢键活化等合成方法学论文和30余篇氟有机化学论文基本来源于德国《应用化学》(国际版)和《美国化学杂志》。本文汇集了中国有机化学家两年中合成的150多个具有生物活性和化学结构多样性的天然产物,其中不乏具有高度挑战性的复杂天然分子。在近两年中中国有机化学家从陆地和海洋的生物体内发现各种不同类型新天然产物90多个。