The biology and chemistry of the zoanthamine alkaloids

Marine natural products have long played an important role in natural products chemistry and drug discovery. Mirroring the rich variety and complicated interactions of the marine environment, the substances isolated from sea creatures tend to be incredibly diverse in both molecular structure and biological activity. The natural products isolated from the polyps of marine zoanthids are no exception. The zoanthamine alkaloids, the first of which were isolated over 20 years ago, are of particular interest to the synthetic community because they feature a novel structural framework and exhibit a broad range of biological activities. In this Review, we summarize the major contributions to understanding the zoanthamine natural products with regard to their isolation and structure determination, as well as studies on their biological activity and total synthesis.     

The chemistry and biology of organic guanidine derivatives

Organic guanidine compounds are reviewed, with emphasis on natural products isolation, identification, synthesis and biological activities. The literature survey includes purely synthetic guanidine derivatives, guanidine alkaloids and non-ribosomal peptides from bacteria and cyanobacteria, as well as related compounds isolated from marine and terrestrial invertebrates and higher plants.     

海洋二聚吡咯-咪唑类生物碱

近20年来,大量二聚吡咯-咪唑类生物碱从海绵中分离得到,并表现出良好的生理活性。而这些分离上的进展,为确定该类化合物结构提供新的信息,更促进了生源合成的研究发展。这类化合物因其结构新颖性、多样性以及良好的生理活性而成为合成化学家们关注的焦点。由于该类天然产物分子结构的复杂性、分子中的高氮数(N/C ≈ 1 ∶2)以及不确定的绝对构型,使得这类分子的合成十分具有挑战性。本文主要综述了海洋二聚吡咯-咪唑类生物碱的分离和合成进展。     

Misenine,a Novel Macrocyclic Alkaloid with an Unusual Skeleton from the Mediterranean Sponge Reniera sp

PolycycJic marine alkaloids containing 3-alkylpyridine or partially reduced 3-alkylpyridine as basic building blocks represent an emerging and intriguing group of bioactive natural products from marine sponges. Since halitoxin,² the first example of this kind of alkaloid, was reported in 1978, many related alkaloids have been discovered from sponges of the order Haplosclerida. All of these alkaloids, in spite of formally exhibiting quite different frameworks, could biogeneticaliy derive from bis-3-alkylpyridine or reduced bis-3-alkylpyridine units. In the last decade, the knowledge of this fascinating group of compounds has increased remarkably. A recent review has exhaustively studied occurrence, distribution, plausible biogenetic origin and relatedness, as well as biological activities, of 3-alkylpyridine derived marine alkaloids.³     

虎皮楠生物碱研究进展

虎皮楠生物碱结构多变且具有复杂的多环骨架, 该类生物碱奇特的多环结构使其成为化学和生物合成研究的热点之一. 最近的关于虎皮楠生物碱的综述是由Kobayashi和Morita等于2003年报道的, 文章对1987到2002年间虎皮楠生物碱的研究进行了概括. 其后又有从11种虎皮楠植物中分离到的60多个新的虎皮楠生物碱报道, 其中三分之二是由中国学者从分布于中国的虎皮楠植物中分离得到. 这些新生物碱有的骨架类型已知, 有的骨架新颖. 故对这些新生物碱的结构分类、可能的生物合成途径和生物活性进行了综述. 对生物碱的分类基本按照以前提出的方法, 但增加了7种新的骨架类型. 对各种骨架的结构特点及在生物合成中的相互关系也进行了讨论.     

海鞘中抗肿瘤活性物质的研究概况

海鞘的生理活性物质是海洋天然产物化学中引人注目的研究领域之一。近年来，从海鞘中分离出许多结构新颖、生理活性显著的新化合物，引起了有机化学家和药物学家等的日益重视。本文按肽、稠环芳香族生物碱、脂肪族生物碱、多硫化物、大环内酯、萜类化合物等化学结构分类综述海鞘抗肿瘤成分的研究进展。     

Stereoselective synthesis of (Z)-axino- and (Z)-debromoaxinohydantoin

(Z)-Axinohydantoin and (Z)-debromoaxinohydantoin, two pyrrole-imidazole alkaloids isolated from different marine sponges, possess moderate activities in inhibiting the progress of the cell cycle at different phases. A stereoselective synthesis of both natural products was achieved. The key step in the synthetic pathway was the installation of the hydantoin northern ring by using 1-benzoyl-2-methylsulfanyl-1,5-dihydroimidazol-4-one.     

The pursuit of palau'amine

Since its discovery in 1993, the marine natural product palau'amine has intrigued natural product chemists. Its exotic molecular architecture and purported bioactivity made it an ideal target for synthesis. However, as the years went by and related marine alkaloids were isolated, a skeptical eye was cast on the structure of palau'amine; recently these suspicions were confirmed and the structure of palau'amine revised. This Minireview gives a careful overview of the structural revision and its ramifications to both its biogenesis and total synthesis.     

Synthesis of bioactive nitrogen heterocycles from marine organisms

Recently many bioactive indole alkaloids have been isolated from marine organisms. Many of them have novel ring systems which are not found in the indole alkaloids isolated from higher plants and molds on the land. We have chosen β-carboline alkaloids, eudistomins and manzamines, as targets for total synthesis.     

Concise synthesis of (+)-serinolamide A

Serinolamide A, isolated from a species of marine cyanobacteria, exhibits a moderate agonist effect and selectivity for the CB₁ cannabinoid receptor, which is unusual for marine natural products. Herein, we reported a highly efficient enantiospecific first total synthesis of (+)-serinolamide A from l-serine in nine steps with 30% overall yield. The synthesis method provides a facile, practicable, and economical approach for the preparation of other similar endocanabinoid lipids.     

Enantioselective total syntheses of (-)-palau'amine, (-)-axinellamines, and (-)-massadines

Dimeric pyrrole-imidazole alkaloids represent a rich and topologically unique class of marine natural products. This full account will follow the progression of efforts that culminated in the enantioselective total syntheses of the most structurally ornate members of this family: the axinellamines, the massadines, and palau'amine. A bio-inspired approach capitalizing on the pseudo-symmetry of the members of this class is recounted, delivering a deschloro derivative of the natural product core. Next, the enantioselective synthesis of the chlorocyclopentane core featuring a scalable, catalytic, enantioselective Diels-Alder reaction of a 1-siloxydiene is outlined in detail. Finally, the successful divergent conversion of this core to each of the aforementioned natural products, and the ensuing methodological developments, are described.     

新型海洋双吲哚类生物碱的研究进展

双吲哚类生物碱是近年来分离到的一类很重要的海洋天然产物。由于这类化合物具有新颖的化学结构和多种生理活性,因此它们引起了科学家极大的兴趣。本文综述了近年来新型海洋双吲哚类生物碱的研究进展。     

The Total Synthesis of Isodon Diterpenes

Families of structurally related molecules often provide stimulating targets for organic chemists that are engaged in the development of new methods and strategies for natural product synthesis. While typically focused on specific molecules, these synthetic investigations often lead to generalizable concepts and significant opportunities for learning in a greater sense. Historically well‐investigated families of natural products, such as the prostanoids, indole alkaloids, and macrolide antibiotics, provide ample evidence for the enduring value of these collective activities. In this Minireview, we turn our attention to the polycyclic family of diterpenes isolated from the Isodon genus of plants and provide an account of the recent methods and strategies utilized for their total synthesis.     

Total Synthesis of Suberitines A–D Featuring Tunable Biomimetic Late-Stage Oxidative Dearomatization and Acetalization

Aaptaminoids are a unique family of marine alkaloids bearing a benzo[de][1,6]-naphthyridine core. This work describes the first total synthesis of suberitines A–D ( 1 – 4 ), four typical dimeric natural aaptaminoids, employing a step-saving bidirectional strategy. Key methods applied in the total synthesis include a cationic cascade to construct the bis-isoquinoline(s) with Hendrickson reagent-mediated Friedel-Crafts-type cyclization and eliminative aromatization, and a Bronsted acid-promoted Vilsmeier cyclization to generate the naphthyridine(s). The conditionally tunable PIDA-mediated oxidative dearomatization and subsequent methanolysis or hydrolysis successfully served as a powerful biomimetic tool to elaborate the essential oxygenated functionalities of suberitines A–D ( 1 – 4 ) in proper solvent-combinations at the final stage of total synthesis. The biomimetic proposal employed in the late-stage redox interchanges of related natural products was eventually supported by the isolation of synthetic intermediate 23 a as a natural product from the same natural source. Biological screening revealed that five of the synthetic samples including two natural suberitines and three full-skeleton natural product-like intermediates exhibited low micromolar inhibitory activities against the growth of cancer cell line K562.     

Current Perspectives on Pyrroloiminoquinones: Distribution,Biosynthesis and Drug Discovery Potential

Pyrroloiminoquinones are a group of cytotoxic alkaloids most commonly isolated from marine sponges. Structurally, they are based on a tricyclic pyrrolo[4,3,2-de]quinoline core and encompass marine natural products such as makaluvamines, tsitsikammamines and discorhabdins. These diverse compounds are known to exhibit a broad spectrum of biological activities including anticancer, antiplasmodial, antimicrobial, antifungal and antiviral activities as well as the inhibition of several key cellular enzymes. The resurgence of interest in pyrroloiminoquinones and the convoluted understanding regarding their biological activities have prompted this review. Herein, we provided a concise summary of key findings and recent developments pertaining to their structural diversity, distribution, biogenesis, and their potential as chemical probes for drug development, including a discussion of promising synthetic analogs.     

Formal total synthesis of (±)-cortistatin A

A second-generation synthesis of the pentacyclic core of the cortistatins, a family of rearranged steroidal alkaloids that have recently attracted much attention, is reported. The improved sequence provides access to significant quantities of this key compound, which enabled a formal total synthesis of (±)-cortistatin A by conversion to the key Nicolaou/Hirama dienone. It is anticipated that this new, robust route to the pentacyclic core will facilitate the total synthesis of a range of natural products in the cortistatin family, as well as the construction of key structural analogs to probe the promising biological activity of these important compounds.     

The first syntheses of 3-bromofascaplysin, 10-bromofascaplysin and 3,10-dibromofascaplysin—marine alkaloids from Fascaplysinopsis reticulata and Didemnum sp. by application of a simple and effective approach to the pyrido[1,2-a:3,4-b′]diindole system

A simple and practical approach for the synthesis of the marine sponge pigment fascaplysin was used for the total syntheses of its natural derivatives, the marine alkaloids 3-bromofascaplysin, 10-bromofascaplysin, and 3,10-dibromofascaplysin. The conditions of each step were revised, and as a result these compounds were produced by identical procedures with total yields of 40-43%.     

Progress on the total synthesis of natural products in China: From 2006 to 2010

This paper summarizes the progress on the total syntheses of natural products accomplished in mainland China during the period from 2006 to 2010.The overview focuses on the first total synthesis of natural products of contemporary interest including alkaloids,cyclopeptides and cyclic depsipeptides,macrolides,terpenoids and steroids,saponins and glycosides.The development of novel synthetic strategies and methodologies,and application of new selective synthetic methods in the total syntheses of natural products are included as well.     

Hyrtioseragamines A and B, new alkaloids from the sponge Hyrtios species

Two novel alkaloids with a furo[2,3-b]pyrazin-2(1H)-one moiety and a guanidino group, hyrtioseragamines A (1) and B (2), have been isolated from an Okinawan marine sponge Hyrtios species. The structures of 1 and 2 were elucidated on the basis of spectroscopic data and chemical conversions. Compounds 1 and 2 are the first natural products possessing a furo[2,3-b]pyrazine-related moiety.