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。     

可见光促进的氧化还原催化反应在天然产物全合成中的应用

可见光促进的光氧化还原催化在近年来取得了重要进展, 许多可见光光氧化还原的反应被用于复杂分子的构建. 本文概述了这一领域的最新成果, 重点介绍该策略作为关键步骤在天然产物及类天然产物化合物的全合成中的应用.     

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.     

《天然有机化合物核磁共振碳谱集》(上、下册)

(ISBN 978-7-122-12695-5)本书是全面收集了生物碱类、萜类、皂、苷类、黄酮类、醌类、苯丙素类、甾体类、芳香族类、脂肪族类,木脂素、香豆素、氨基酸和糖类、海洋天然产物、抗生素等2万余种天然有机化合物的核磁共振碳谱数据,每一种化合物都给出了相应的名称、分子式、结构式、测试溶剂和碳的化学位移数据以及参考文献。书后还附有化合物中英文名称索引以及分子式     

天然产物Haouamine A的全合成研究进展

回顾了Haouamine类化合物分离提取和结构鉴定,指出HaouamineA和Haouamine B区别在于茚环中的芳香环的氧化程度.Haouamine类化合物具有良好的抗肿瘤生物活性.综述了2003年至今HaouamineA全合成进展,特别总结了HaouaminA化合物的基本骨架和不对称合成研究,指出构建茚并四氢吡啶环中的二芳基季碳手性中心和高度张力的对环芳烷11元大环是合成的亮点,也是合成Haouamines类生物碱过程中难点.     

《天然有机化合物核磁共振氢谱集》(上、下册)

(ISBN 978-7-122-12700-6)该书全面收集了生物碱类、皂苷类、黄酮类、醌类、单萜类、倍半萜类、二萜类、三萜类、其它萜类、苯丙素类、甾体类、二苯乙烯类、环庚三烯酚酮和脑苷脂类、海洋天然产物类、氨基酸和糖类共17大类1万余种天然有机化合物的氢核磁共振谱数据。每一种化合物都给出了名称、分子式、结构式、~1H的化学位移和偶合常数数据,以及相应的参考文献。书后     

大环二萜天然产物(±)-Mayol的全合成

西松烷型二萜类化合物是一大类广泛分布于松脂、烟草、陆地动物及海洋生物体中的具有十四元碳环骨架的化合物.其结构新颖复杂,且大多具有显著和广谱的生物活性.近几十年来,有关这类化合物的研究已引起了人们的极大兴趣.因此,开展这类天然产物及其类似物的全合成及构效关系的研究不仅具有重要的学术价值,而且具有潜在的应用前景.     

黄烷酮化合物的合成研究进展

黄烷酮化合物是自然界中广泛存在的一类具诸多生理活性的重要化合物，本文对近20年来黄烷酮化合物的合成研究进展进行了综述。     

有机锡化合物在天然产物合成中的应用

综述了有机锡化合物在不同对称合成天然产物中的应用。有机锡化合物应用于天然产物的不对称合成,反应条件温和、活性高,有很高的立体选择性和区域选择性,有广阔的应用前景。     

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。     

中国海洋天然产物合成研究新进展

海洋天然产物合成研究是海洋天然有机化学最活跃的研究领域之一。本文综述中国海洋天然产物合成研究的最新进展,包括海洋环肽、西松烷(烯)和西松烷型二萜内酯、喹啉酮衍生物和三丙酮胺以及柳珊瑚酸类似物等。     

Total Synthesis of Keramamides A and L from a Common Precursor by Late‐Stage Indole Synthesis and Configurational Revision

The marine natural products keramamide A and L, members of the class of anabaenopeptin‐type peptides, were synthesized for the first time by a convergent and flexible route. The installation of the substituted tryptophan moieties was accomplished at the very end of the synthesis on the cyclic peptides, and thus enabled the synthesis of both natural products from one common precursor. The preparation of several epimers clearly indicates that the originally proposed relative configurations of both Keramamides A and L were not correct.     

Total synthesis and determination of the absolute configuration of guadinomines B and C2

This article describes the determination of the absolute configurations of the guadinomines, which are novel cyclic guanidyl natural products that are inhibitors of the type III secretion system (TTSS) of bacteria. Any compound that interrupts the TTSS of bacteria is potentially an ideal anti-infectious drug. The reliable asymmetric synthesis of guadinomines has revealed their absolute configurations, which could not have been defined without this synthetic approach. Our report not only describes the asymmetric total synthesis of the title compounds, but also demonstrates the novel concise synthesis of tri-substituted piperazinone cores as optically pure forms. The novel feature of our method is an intramolecular S(N)2 cyclization that uses PPh(3) and I(2) to construct the unique 5-membered cyclic guanidine substructure.     

Total Synthesis of (+/−)‐Frondosin B and (+/−)‐5‐epi‐Liphagal by Using a Concise (4+3) Cycloaddition Approach

A recently developed (4+3) cycloaddition between dienes and furfuryl alcohols, as precursors of oxyallyl‐type cations, has been used as a key step in the racemic syntheses of two natural products: frondosin B and liphagal. This work demonstrates the synthetic potential of this cycloaddition reaction, and offers a short synthetic route to an interesting family of natural products. A full account of these synthetic studies is presented, further illustrating the mechanism, scope, and limitations of this straightforward synthetic method for seven‐membered rings.     

Advances in the Total Synthesis of Xanthanolide‐Type Sesquiterpenoids

Xanthanolide‐type sesquiterpenoids are a diverse family of natural products isolated primarily from the genus Xanthium (Compositae). The intriguing molecular architectures and biological profiles of these natural products have rendered them attractive targets for total synthesis. This focus review aims to provide an up‐to‐date summary of progress in the chemical synthesis of xanthanolide‐type sesquiterpenoids. Different synthetic strategies to form 5/7‐cis‐ and 5/7‐trans‐bicyclic xanthanolides are presented in chronological order, with an emphasis on the key elements used to forge the characteristic 5/7‐bicyclic cores of the targets. Recent advances in the total syntheses of structurally more complicated polycyclic and dimeric xanthanolides are also discussed.     

Genome Mining of Oxidation Modules in trans‐Acyltransferase Polyketide Synthases Reveals a Culturable Source for Lobatamides

Bacterial trans‐acyltransferase polyketide synthases (trans‐AT PKSs) are multimodular megaenzymes that biosynthesize many bioactive natural products. They contain a remarkable range of domains and module types that introduce different substituents into growing polyketide chains. As one such modification, we recently reported Baeyer–Villiger‐type oxygen insertion into nascent polyketide backbones, thereby generating malonyl thioester intermediates. In this work, genome mining focusing on architecturally diverse oxidation modules in trans‐AT PKSs led us to the culturable plant symbiont Gynuella sunshinyii, which harbors two distinct modules in one orphan PKS. The PKS product was revealed to be lobatamide A, a potent cytotoxin previously only known from a marine tunicate. Biochemical studies show that one module generates glycolyl thioester intermediates, while the other is proposed to be involved in oxime formation. The data suggest varied roles of oxygenation modules in the biosynthesis of polyketide scaffolds and support the importance of trans‐AT PKSs in the specialized metabolism of symbiotic bacteria.     

Type S Non-Ribosomal Peptide Synthetases for the Rapid Generation of Tailormade Peptide Libraries**

Bacterial natural products in general, and non-ribosomally synthesized peptides in particular, are structurally diverse and provide us with a broad range of pharmaceutically relevant bioactivities. Yet, traditional natural product research suffers from rediscovering the same scaffolds and has been stigmatized as inefficient, time-, labour- and cost-intensive. Combinatorial chemistry, on the other hand, can produce new molecules in greater numbers, cheaper and in less time than traditional natural product discovery, but also fails to meet current medical needs due to the limited biologically relevant chemical space that can be addressed. Consequently, methods for the high throughput generation of new natural products would offer a new approach to identifying novel bioactive chemical entities for the hit to lead phase of drug discovery programs. As a follow-up to our previously published proof-of-principle study on generating bipartite type S non-ribosomal peptide synthetases (NRPSs), we now envisaged the de novo generation of non-ribosomal peptides (NRPs) on an unreached scale. Using synthetic zippers, we split NRPSs in up to three subunits and rapidly generated different bi- and tripartite NRPS libraries to produce 49 peptides, peptide derivatives, and de novo peptides at good titres up to 145 mg L⁻¹. A further advantage of type S NRPSs not only is the possibility to easily expand the created libraries by re-using previously created type S NRPS, but that functions of individual domains as well as domain-domain interactions can be studied and assigned rapidly.     

用组合化学建立天然产物类似物库

天然产物是药物先导化合物的重要来源.组合化学技术在天然产物的研究中起着越来越重要的作用.目前已构建并合成了许多以天然产物为模板的化合物库,为基于天然产物的药物研究开辟了广阔的空间.     

Antibacterial Natural Products in Medicinal Chemistry—Exodus or Revival?

To create a drug, nature's blueprints often have to be improved through semisynthesis or total synthesis (chemical postevolution). Selected contributions from industrial and academic groups highlight the arduous but rewarding path from natural products to drugs. Principle modification types for natural products are discussed herein, such as decoration, substitution, and degradation. The biological, chemical, and socioeconomic environments of antibacterial research are dealt with in context. Natural products, many from soil organisms, have provided the majority of lead structures for marketed anti-infectives. Surprisingly, numerous "old" classes of antibacterial natural products have never been intensively explored by medicinal chemists. Nevertheless, research on antibacterial natural products is flagging. Apparently, the "old fashioned" natural products no longer fit into modern drug discovery. The handling of natural products is cumbersome, requiring nonstandardized workflows and extended timelines. Revisiting natural products with modern chemistry and target-finding tools from biology (reversed genomics) is one option for their revival.