A semisynthesis of 3'-O-ethyl-5,6-dihydrospinosyn J based on the spinosyn A aglycone

• Kai Zhang,
• Shenglan Liu,
• Anjun Liu,
• Hongxin Chai,
• Jiarong Li and
• Lamusi A

Beilstein J. Org. Chem. 2017, 13, 2603–2609, doi:10.3762/bjoc.13.257

• opportunities to synthesize spinosyn analogues and rhamnose derivatives. Keywords: 3-O-ethyl-2,4-di-O-methylrhamnose; protecting groups; semisynthesis; spinetoram; spinosyn A; Introduction Spinosyns, a large family of secondary metabolites produced by aerobic fermentation of Saccharopolyspora spinosa, are a

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• ]. More recently, BcGT1 from Bacillus subtilis was shown to efficiently catalyse the glucosylation of thiol-containing acceptors [32]. C-Glycosyltransferases For more than 50 years, C-glycosides have been identified in plants [33][34] as secondary metabolites. At least 5 families of aromatic aglycones

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• cytotoxicity against the HL-60 tumor cell line. Keywords: directed ortho/remote metalation; Eaton’s reagent; isoquinolines; Suzuki cross-coupling; Introduction Benzylisoquinoline alkaloids represent a very large group of plant secondary metabolites, which includes about 2,500 known structures. Besides simple

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• Liang-Liang Wang Andreas Kirschning Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz University Hannover, Schneiderberg 1b, 30167 Hannover, Germany 10.3762/bjoc.13.124 Abstract The elansolids A1–A3, B1, and B2 are secondary metabolites formed by the gliding

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• Isoprenoid natural products are one of the most structurally diverse groups of primary and secondary metabolites in all kinds of organisms. Moreover, they represent an invaluable source of bioactive natural products. Prominent representatives of these compounds are taxol [1] (paclitaxel, anticancer drug

• identify new isoprenoids of industrial relevance essential oil extracts are screened for bioactive properties that may furnish future drugs [7][8]. Harnessing isoprenoid compounds for large-scale industrial purposes can be hampered due to low natural occurrence. Being mostly secondary metabolites

• for Class III cyclases. Class III-type terpene synthases appear to be exclusively responsible for angiosperm secondary metabolites of mono-, sesqui- and diterpene structure and contain a highly conserved RR(x)8W-motif [47][49]. The terpene formation performed by Class I-type enzymes occurs via

Lipids: fatty acids and derivatives, polyketides and isoprenoids

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2017, 13, 793–794, doi:10.3762/bjoc.13.78

• African reed frog that are likely amphibian signaling compounds [1]. Sensu lato, and this is the definition relevant to this Thematic Series: lipids include all kinds of apolar (or less polar) primary and secondary metabolites, including molecules that are formed via fatty acid biosynthesis, the

Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium longicirrum, (Gastropoda, Heterobranchia, Nudibranchia)

• Alexander Bogdanov,
• Cora Hertzer,
• Stefan Kehraus,
• Samuel Nietzer,
• Sven Rohde,
• Peter J. Schupp,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2017, 13, 502–519, doi:10.3762/bjoc.13.50

• chemistry. Herein we report the isolation of a total of 19 secondary metabolites from a single specimen of this species, i.e., steroids 1–4, cembranoid diterpenes 5–13, complex biscembranoids 14 and 15, and the chatancin-type diterpenes 16–19. These compounds resemble those from soft corals of the genus

• octocorallian food also offers a wide spectrum of terpenoid chemistry, which is incorporated and stored by Phyllodesmium. Only few chemical investigations were undertaken on Phyllodesmium species [10][11][12][13][14][15], describing mostly terpenoid secondary metabolites. Indirect evidence suggests that these

• yielding 11 fractions. 1H NMR analysis of these indicated the presence of chemically diverse secondary metabolites in the major fractions 3–8, whereas the hydrophilic fractions 1 and 2 merely contained sugars and the lipophilic ones, i.e., 9–11 simple lipids. Detailed UPLC–HRMS investigation was thus

Biosynthetic origin of butyrolactol A, an antifungal polyketide produced by a marine-derived Streptomyces

• Enjuro Harunari,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2017, 13, 441–450, doi:10.3762/bjoc.13.47

• diverse secondary metabolites with pharmaceutically useful bioactivities. Importantly, members of the genus Streptomyces have been the main source of drug discovery programs due to their high capacity in secondary metabolism including polyketides, peptides, terpenoids, alkaloids, and amino acid

• /carbohydrate/nucleic acid derivatives [1][2]. One of the largest groups of bacterial secondary metabolites is polyketide from which a range of clinically used drugs have been developed. Polyketides still remain in the focus of drug development because of their structural complexity that can provide attractive

• polyketide. Examples of similar but shorter polyol carbon chains are ossamycin [19], IB-96212 [20], and antifungalmycin [21], all of which are the secondary metabolites of actinomycetes (Figure 3). In our investigation on secondary metabolites of marine actinomycetes, butyrolactol A (1) was found to be

Versatile synthesis of the signaling peptide glorin

• Robert Barnett,
• Daniel Raszkowski,
• Thomas Winckler and
• Pierre Stallforth

Beilstein J. Org. Chem. 2017, 13, 247–250, doi:10.3762/bjoc.13.27

• form a multicellular organism. Eventually, they culminate in fruiting bodies to spread some of the population as dormant spores into the environment. Secondary metabolites often constitute the key signaling molecules in these developmental processes [3][4]. For instance, aggregation of the amoebae is

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• secondary metabolites contains two 2,5-trans-substituted THF ring systems (Scheme 7) [66][67]. Despite significant efforts from various research groups, it took more than two decades from its isolation and characterization to the publication of its first total synthesis by Carter and co-workers in 2012 [67

Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291

• Peng Zhang,
• Xiao-Ming Li,
• Xin-Xin Mao,
• Attila Mándi,
• Tibor Kurtán and
• Bin-Gui Wang

Beilstein J. Org. Chem. 2016, 12, 2012–2018, doi:10.3762/bjoc.12.188

• prolific source of bioactive secondary metabolites of diverse structures, including, for example, semiviriditoxin derivatives with antibacterial activity [3], cornexistin and hydroxycornexistin with herbicidal activity [4], and paecilocins with antibacterial activity [5]. During our ongoing effort to

• search for structurally unique and bioactive secondary metabolites from marine fungi, especially from marine alga-derived fungi [6][7][8], we discovered evident DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity and diverse antimicrobial activities in the EtOAc extract from Paecilomyces

• continues to be a prolific source of bioactive secondary metabolites with diverse structures. In this paper, two indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivatives, varioloids A (1) and B (2), were isolated from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291. The

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• to produce peptidic secondary metabolites, including non-ribosomal peptide synthetases [1][2] (NRPSs) and diketopiperazine-forming cyclases [3][4]. Alternatively, peptides synthesised by the ribosome can be post-translationally modified into secondary metabolites [5]. These are termed ribosomally

• to AMP and pyrophosphate [43]. The function of this highly conserved “non-TOMM” protein has yet to be identified, but it indicates that amide activation by ATP may not be confined to the biosynthesis of secondary metabolites or purines. Ec-YcaO also lacks a partner C-protein, which is also the case

Antibacterial structure–activity relationship studies of several tricyclic sulfur-containing flavonoids

• Lucian G. Bahrin,
• Henning Hopf,
• Peter G. Jones,
• Laura G. Sarbu,
• Cornelia Babii,
• Alina C. Mihai,
• Marius Stefan and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2016, 12, 1065–1071, doi:10.3762/bjoc.12.100

• [1][2]. Clearly, the development of new types of antibiotics is strongly needed [3]. Flavonoids are a diverse class of plant secondary metabolites that share the same C6–C3–C6 backbone. The great structural diversity of these compounds results in a wide range of biological activities. Flavonoids can

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• given elsewhere [18]. Secondary metabolites from myxobacteria Members of the order Myxococcales are famous for their ability to produce secondary metabolites of diverse chemical nature with the capability to exert different biological effects [19][20]. Detailed descriptions of myxobacteria-derived

• metastatic breast cancer treatment, demonstrating the therapeutic potential of myxobacterial secondary metabolites [29][30][31]. This drug has also been assessed as chemotherapeutic agent in pancreatic lymphoma showing promising results and tolerable toxicity [32]. Over time, different strategies have been

• designed to tackle the sometimes cumbersome task of finding bioactive secondary metabolites of bacterial origin, i.e., mainly bioactivity- or chemistry-guided methods. An additional approach, complementary to the latter, arose in the late 1990s, when the first microbial genomes were sequenced, allowing

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• biosynthesis. This review will focus on muraymycins as a subclass of nucleoside antibiotics, covering their mode of action, synthetic approaches as well as SAR studies on several derivatives. Furthermore, first insights into the biosynthesis of these Streptomyces-produced secondary metabolites will be

Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

• Guozheng Huang,
• Simon Schramm,
• Jörg Heilmann,
• David Biedermann,
• Vladimír Křen and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 662–669, doi:10.3762/bjoc.12.66

• combine the structural moieties of flavonoids and phenylpropanoids (lignans). Among the group of flavonolignans, the medicinally most important ones can be found in Silybum marianum (L.) Gaertn., the milk thistle. The phenolic secondary metabolites of this plant have been intensively studied due to their

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• known secondary metabolites of M. xanthus DK1622 show a wide range of biological activities and can hence be expected to fulfill different ecological functions. The yellow DKxanthenes, for instance, play a crucial role in spore maturation during fruiting body formation [63]. They were also shown to

• completely ignored in the field. It is therefore no surprise that to date only three classes of secondary metabolites have been reported from this genus (Figure 6). Siphonazole and its O-methyl derivative were the first natural products to be isolated from a Herpetosiphon strain [125]. The two compounds

• exceed the most closely related non-predatory species, as shown for the myxobacteria, a distinctive feature between predatory and non-predatory strains is the density of biosynthetic loci. In other words, families of genes encoding the production of secondary metabolites were consistently found to be

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• , production by a fungus and modification of the metabolites by plant enzymes is also possible. Further α-pyrone plant secondary metabolites are ellagitannins and ellagic acid (22) [27] (Figure 4). These metabolites are important constituents of different foods, e.g., berries, nuts, medicinal plants and

Natural products from microbes associated with insects

• Christine Beemelmanns,
• Huijuan Guo,
• Maja Rischer and
• Michael Poulsen

Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34

• , Universitetsparken 15, Building 3, 1st floor, 2100 Copenhagen East, Denmark 10.3762/bjoc.12.34 Abstract Here we review discoveries of secondary metabolites from microbes associated with insects. We mainly focus on natural products, where the ecological role has been at least partially elucidated, and/or the

• species [12][13][14][15][16][17]. As a response to these threats, many insects have evolved defensive strategies, including mechanical and behavioral defense, complex immune systems, and the use of bioactive secondary metabolites produced by residing mutualists [12][13][14][15][16][17][24][25][26]. The

• the brood cell with the protective symbiont, beewolf females ensure that the larvae take up the symbionts from the surrounding soil while spinning the cocoon. Using high resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) spectroscopy, the protective secondary metabolites were

Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin

• Waratchada Sangpheak,
• Jintawee Kicuntod,
• Roswitha Schuster,
• Thanyada Rungrotmongkol,
• Peter Wolschann,
• Nawee Kungwan,
• Helmut Viernstein,
• Monika Mueller and
• Piamsook Pongsawasdi

Beilstein J. Org. Chem. 2015, 11, 2763–2773, doi:10.3762/bjoc.11.297

• three different cancer cell lines. The overall results suggested that solubilities and bioactivities of both flavanones were increased by complexation with methylated β-CDs. Keywords: binding energy; bioactivity; cyclodextrins; hesperetin; naringenin; Introduction Flavonoids are secondary metabolites

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• a large group of structurally diverse secondary metabolites. Among these natural products, Xenia diterpenoids or xenicanes represent a unique family with intriguing structural features and diverse biological activities. Many xenicanes display significant cytotoxic and antibacterial activity and are

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• understanding of biosynthesis. As demonstrated in this article, the usage of isotopes is not at all old-fashioned, but continues to give important insights into biosynthetic pathways of secondary metabolites. This review with 85 cited references is structured by separate discussions of compounds from different

• reductase [16], aflatoxin B1 (2) [17] and the potent antifungal agent amphotericin B (3) [18], which affects membrane integrity. The products of polyketide synthases (PKS) belong to the first secondary metabolites that were investigated using isotopically labeled compounds [19]. Feeding experiments using

The marine sponge Agelas citrina as a source of the new pyrrole–imidazole alkaloids citrinamines A–D and N-methylagelongine

• Christine Cychon,
• Ellen Lichte and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2029–2037, doi:10.3762/bjoc.11.220

• fascinating example of a large variety of secondary metabolites produced exclusively by marine sponges. To date, more than 150 PIAs have been isolated mainly from various species of the families Agelasidae, Axinellidae, Dyctionellidae, and Hymeniacidonidae and some of them show promising biological activities

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• order to improve food production, healthcare and their living space, humans have developed and improved techniques to study and understand the environment. One of such interests is the chemical investigation of marine organisms, which can provide many compounds belonging to a large class of secondary

• metabolites. It is well known that these chemicals play specific roles for their host with respect to communication [1], sexual attraction [2] and defense [3]. Marine biodiversity has provided around three thousand new chemicals, the most predominant of which are associated with polyketides, peptides

Synthesis and spectroscopic properties of β-triazoloporphyrin–xanthone dyads

• Dileep Kumar Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2015, 11, 1434–1440, doi:10.3762/bjoc.11.155

• diporphyrin analogues [20][28][29][30]. Xanthene-9H-ones are an important class of oxygen-containing heterocycles and are mainly found as secondary metabolites in higher plants and microorganisms. The naturally occurring and synthetic xanthones possess diverse pharmacological activities [31][32][33][34