活性天然产物和结构多样性类天然产物的合成

天然产物骨架的复杂性和丰富的官能团化赋予了天然产物类化合物独有的生物学活性,因此天然产物作为药物研究的先导化合物有其无法替代的独特性质,比如紫杉醇、红霉素和利福霉素帮助科学家们理解重要的生物过程。以往化学家对天然产物独有情钟,但仅仅以合成天然产物本身为最终目的。今天,化学家们开始利用传统的合成方法来制备结构多样性的类天然产物化合物。这种利用合成手段制备的小分子化合物在生物学的基础研究和药物研究中将起到关键的作用。     

石松生物碱集成合成的研究进展

鉴于同一家族天然产物在化学结构和生物合成途径上的相关性,2011年Mac Millan等提出利用相同或相似的关键中间体快速高效合成天然产物家族化合物的集成合成策略,近年来该策略被应用于多个家族天然产物的合成中.石松生物碱是一类结构奇特且复杂多样的生物碱,部分成员化合物表现出良好的生物活性.综述了国内外有机合成化学家对石松生物碱家族化合物的集成合成研究进展.     

自由基串联反应策略构筑吲哚并[1,2-a]喹啉

<正>含氮杂环化合物广泛存在于天然产物、合成药物、功能材料等多个领域.鉴于其独特的生理活性和功能,开发新型高效的合成策略高效构建结构多样性的含氮杂环一直是合成化学家追求的目标~([1]).近年来,自由基串联环化反应作为一种可靠、方便的构环策略,越来越受到人们的关注.虽然在过去十几年里合成化学家利用"自由基串联环化策略"合成了各种含氮杂环骨架,但是     

螺二萘类天然产物化学研究的新进展

螺二萘是一类由两个萘环通过螺缩酮或联二萘醚形式连在一起并高度氧化的天然产物,它们结构新颖复杂、手性中心多,又具有广泛的生物活性,成为近年来合成化学家研究的热门课题.结合本课题组近年来在该领域的研究工作,系统综述了自2010年以来螺二萘类天然产物化学研究取得的新进展,包括新发现的62个天然产物结构、螺二萘类化合物的合成、生物合成途径、生物活性以及结构-活性关系等,旨在进一步推进我国天然产物化学及先导结构优化等在新医药、新农药创制方面的研究工作.     

巴西木素类天然产物的合成研究进展

巴西木素类型天然产物是从中药苏木(Caesalpinia sappan)中分离得到的一类化合物,因其独特的结构和良好的生物活性而成为合成化学家关注的焦点.目前,已有许多关于这类天然产物合成的报道.我们主要对巴西木素类型天然产物的合成研究进展进行了综述.     

三氯化铟催化构建多环吲哚啉结构的[2+2+2]串联环化反应

正Angew.Chem.Int.Ed.2016,55,9224~9228吲哚类生物碱是一类重要的天然产物,由于其数目众多,结构较复杂,同时往往具有显著的生理活性,因此一直备受合成化学家以及药物化学家的青睐.最近,人们发现以malagashanine和11-demethoxy-myrtoidine为代表的一     

海洋天然产物Indoxamycins A和B的全合成

<正>Angew. Chem. Int. Ed. 2019, 58, 6659～6662结构新颖、生物活性多样化的海洋天然产物,已成为新药研发的重要来源. 2009年, Sato等从海洋放线菌中分离得到一类新型聚酮类天然产物indoxamycins A～F.由于其独特的结构特点以及潜在的生物活性,该类天然产物吸引了各国合成化学家的关注.南开大学元素有机化学国家重点实验室梁广鑫课题组以廉价易得的R-香芹酮为原料,利     

海洋天然产物化学的进展

海洋天然产物化学是化学和生物学的边缘学科,是天然有机化学的一个重要领域。自从1964年河豚毒素(tetrodotoxin)的结构被阐明后,化学家们对这个学科产生了极大的兴趣,并且积极地开展了研究工作,对更多的海洋生物进行了新化合物的探讨。七十年代以来,由于有了分离复杂混合物的研究工具和对很少量物质的结构进行快速测定的现代化仪器,海洋天然产物化学才得到迅速的发展。海洋天然产物化学主要是研究海洋天然产物的二级代谢物,碳水化合物、氨基酸及其聚合物被认为是有生命物质的成分,即一级代谢物,则是生物化学研究的领域。     

瑞香烷型二萜天然产物的合成进展

瑞香烷型二萜类天然产物拥有5/7/6三环骨架的复杂分子结构, 含有多个手性中心, 通常在C3、C4、C5、C9、C13、C14、C20等位置含有手性羟基; 其中, 诸多化合物在C9、C13、C14位置的手性羟基之间形成特定的原酸酯结构. 该类天然产物在抗HIV、抗癌、抗白血病、亲神经性、杀虫、细胞毒性等方面显示显著的生物活性. 瑞香烷型的密集的高氧化数的多环骨架和其引人注目的生物活性吸引了众多研究者的合成兴趣, 尽管迄今为止成功的全合成报道依然鲜见, 但合成化学家对其多环骨架的构建已发展了大量有益的策略和方法, 在此对相关合成工作进行归纳综述.     

吲唑酮化合物合成研究进展

吲唑酮作为氮杂环分子当中的重要一员,其分子骨架不仅是有机合成当中的重要中间体,还是许多天然产物和药物分子的核心结构。因此,该类化合物的高效合成一直是合成化学家们的研究热点。本文综述了近二十年来利用过渡金属、高价碘、酸、碱、光、过氧化物以及付-克环化等方法合成吲唑酮骨架的研究进展并展望了吲唑酮化合物合成的研究方向和应用前景     

Enzymatic functionalization of carbon-hydrogen bonds

The development of new catalytic methods to functionalize carbon-hydrogen (C-H) bonds continues to progress at a rapid pace due to the significant economic and environmental benefits of these transformations over traditional synthetic methods. In nature, enzymes catalyze regio- and stereoselective C-H bond functionalization using transformations ranging from hydroxylation to hydroalkylation under ambient reaction conditions. The efficiency of these enzymes relative to analogous chemical processes has led to their increased use as biocatalysts in preparative and industrial applications. Furthermore, unlike small molecule catalysts, enzymes can be systematically optimized via directed evolution for a particular application and can be expressed in vivo to augment the biosynthetic capability of living organisms. While a variety of technical challenges must still be overcome for practical application of many enzymes for C-H bond functionalization, continued research on natural enzymes and on novel artificial metalloenzymes will lead to improved synthetic processes for efficient synthesis of complex molecules. In this critical review, we discuss the most prevalent mechanistic strategies used by enzymes to functionalize non-acidic C-H bonds, the application and evolution of these enzymes for chemical synthesis, and a number of potential biosynthetic capabilities uniquely enabled by these powerful catalysts (110 references).     

Natural Product Synthesis at the Interface of Chemistry and Biology

Nature has evolved to produce unique and diverse natural products that possess high target affinity and specificity. Natural products have been the richest sources for novel modulators of biomolecular function. Since the chemical synthesis of urea by Wöhler, organic chemists have been intrigued by natural products, leading to the evolution of the field of natural product synthesis over the past two centuries. Natural product synthesis has enabled natural products to play an essential role in drug discovery and chemical biology. With the introduction of novel, innovative concepts and strategies for synthetic efficiency, natural product synthesis in the 21st century is well poised to address the challenges and complexities faced by natural product chemistry and will remain essential to progress in biomedical sciences.     

Endeavors to Access Molecular Complexity: Strategic Use of Free Radicals in Natural Product Synthesis

Free radicals, which in the past were considered unruly chemical species, have become manageable and indispensable for synthetic organic chemistry. The unique nature of free radicals has allowed practitioners in organic synthesis to design flexible approaches to produce various materials ranging from small molecules to polymers. The present Personal Account describes the author's endeavors to create molecular complexity by the strategic use of free radicals, with an emphasis on the synthesis of bioactive natural products.     

Applications of total synthesis toward the discovery of clinically useful anticancer agents

This tutorial review provides a historical sampling of synthetic efforts undertaken in our laboratory, which have led to the total syntheses of a range of small molecule natural products of potential interest in oncology. It has become evident that natural products, and structures clearly derivable from natural products, have a remarkable record in the treatment of cancer at the clinical level. It is likely that, with the growing power of chemical synthesis, small molecule natural products will play a continuing role in providing lead anticancer compounds.     

核苷二磷酸糖的合成研究进展

核苷二磷酸糖在结构上是由1分子的糖或糖的衍生物和1分子的核苷二磷酸所组成,它是糖基转移酶的供体底物之一。糖基转移酶正被越来越多的应用于制备寡糖、糖缀合物和含糖基天然产物,因此研究核苷二磷酸糖的有效合成方法是很有必要的。本文总结了合成核苷二磷酸糖的各种化学法和酶法。     

Emerging Strategies for the Total Synthesis of Inorganic Nanostructures

New synthetic innovations are rapidly being developed to address the demand for complex, next‐generation nanomaterials with rigorously controlled architectures and interfaces. This Review highlights key strategies for the chemical transformation and stepwise synthesis of multicomponent inorganic nanostructures, with the existing nanoscale transformations categorized into classes of reactions that are related to those used in the synthesis of organic molecules. The application of concepts used in molecular synthesis—including site‐selectivity, regio‐ and chemoselectivity, orthogonal reactivity, coupling reactions, protection/deprotection strategies, and procedures for separation and purification—to nanoscale systems is emphasized. Collectively, the resulting synthetic concept represents an emerging model for the synthesis of complex inorganic nanostructures on the basis of the guiding principles that underpin the multistep total synthesis of complex organic molecules and natural products.     

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。     

Synthesis of Cytotoxic Palmerolides

The chemical synthesis of the palmerolides is the subject of this review. The palmerolides are a family of Antarctic marine natural products, many of which display potent and selective cytotoxicity against melanoma cells. The confluence of promising bioactivities, limited natural supplies, and complex structures makes the palmerolides exciting targets for chemical synthesis. To date, several approaches have been reported, and a consensus strategy based on convergent fragment assembly has emerged. Collective wisdom from myriad approaches reviewed here may enable hybrid strategies capable of delivering larger amounts of synthetic palmerolides to support continued biological studies. Considering the relative lack of options for melanoma chemotherapy and the intriguing activity profile of the palmerolides, efforts aimed at developing an efficient, gram‐scale synthesis of palmerolide A and congeneric structures should be given a high priority.     

Recent advances in the synthesis of new glycopeptide antibiotics

The vancomycin family of glycopeptide antibiotics has been inspiring research in the field of synthetic chemistry since the 1980s. Recent studies have moved away from the focus of total synthesis into new territory: the design and evaluation of novel compounds based on the natural products which exhibit improved antibacterial activity. Modern approaches to drug synthesis draw together investigations into the nature of the binding environment, and innovative synthetic methodologies which provide solutions to the challenging structural features and stereochemistry associated with this intriguing class of compounds. New analogues, derivatives and dimers of the natural products, as well as recent successes in the total synthesis of the complestatins are described in this tutorial review, covering literature from the last decade.     

Natural products synthesis: enabling tools to penetrate Nature's secrets of biogenesis and biomechanism

Selected examples from our laboratory of how synthetic technology platforms developed for the total synthesis of several disparate families of natural products was harnessed to penetrate biomechanistic and/or biosynthetic queries is discussed. Unexpected discoveries of biomechanistic reactivity and/or penetrating the biogenesis of naturally occurring substances were made possible through access to substances available only through chemical synthesis. Hypothesis-driven total synthesis programs are emerging as very useful conceptual templates for penetrating and exploiting the inherent reactivity of biologically active natural substances. In many instances, new enabling synthetic technologies were required to be developed. The examples demonstrate the often untapped richness of complex molecule synthesis to provide powerful tools to understand, manipulate and exploit Nature's vast and creative palette of secondary metabolites.