Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

• Jessica Matthias,
• Thines Kanagasundaram,
• Klaus Kopka and
• Carsten S. Kramer

Beilstein J. Org. Chem. 2019, 15, 2333–2343, doi:10.3762/bjoc.15.226

• microscopy [2][3][4][5][6][7][8][9], as direct probes for various biomolecules [10][11][12][13] or as sensors for metal ions [14][15][16][17][18], pH [16], voltage [19] or metabolites [20][21][22][23]. Several attempts were made, partially supported by DFT calculations, to correlate the dyes’ structural

Isolation and biosynthesis of an unsaturated fatty acid with unusual methylation pattern from a coral-associated bacterium Microbulbifer sp.

• Amit Raj Sharma,
• Enjuro Harunari,
• Tao Zhou,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2327–2332, doi:10.3762/bjoc.15.225

• secondary metabolites have received lesser attention [3]. To date, a couple of new compounds were discovered from soft coral-associated bacteria such as pseudoalteromones from Pseudoalteromonas isolated from the cultured octocoral Lobophytum crassum [4][5] and macrolactin V from Bacillus amyloliquefaciens

• of metabolites in a marine-derived Microbulbifer sp. led to the discovery of a unique unsaturated fatty acid, (2Z,4E)-3-methyl-2,4-decadienoic acid (1) in which the carbon originated from the carbonyl carbon of an acetate unit is methylated, providing a quite rare case of C-methylation pattern in

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• relationship with their plant hosts [1], which is mediated by secondary metabolites [2]. In 2005, Torta and co-workers reported the isolation of six meroterpenoid natural products, acremines A–F from A20, a strain of Acreonium byssoides, isolated from grapevine leaves that were artificially inoculated with

Isolation of fungi using the diffusion chamber device FIND technology

• Benjamin Libor,
• Henrik Harms,
• Stefan Kehraus,
• Ekaterina Egereva,
• Max Crüsemann and
• Gabriele M. König

Beilstein J. Org. Chem. 2019, 15, 2191–2203, doi:10.3762/bjoc.15.216

• Benjamin Libor Henrik Harms Stefan Kehraus Ekaterina Egereva Max Crusemann Gabriele M. Konig Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany 10.3762/bjoc.15.216 Abstract Fungi are an important source of bioactive metabolites. The Fungal one-step

• of them being the marine-adapted fungal strain Heydenia cf. alpina. The latter produced two new terpenoids, which are the first secondary metabolites from this genus. Keywords: FIND; fungal one-step isolation device; Heydenia cf. alpina; natural products; terpenes; Introduction Natural products

• antibiotics (e.g., cephalosporins), immunosuppressants (e.g., mycophenolic acid) and immunomodulators (e.g., fingolimod), as well as cholesterol lowering agents (statins). Generally, fungal metabolites were shown to have antiviral, cytotoxic, antineoplastic, cardiovascular, anti-inflammatory, immune

Genome mining in Trichoderma viride J1-030: discovery and identification of novel sesquiterpene synthase and its products

• Xiang Sun,
• You-Sheng Cai,
• Yujie Yuan,
• Guangkai Bian,
• Ziling Ye,
• Zixin Deng and
• Tiangang Liu

Beilstein J. Org. Chem. 2019, 15, 2052–2058, doi:10.3762/bjoc.15.202

• that has received considerable attention as an effective biocontrol agent against two fungal pathogens, Fusarium oxysporum f. sp. adzuki and Pythium arrhenomanes, infecting soybean. This fungus is a competent mycoparasite and strong producer of secondary metabolites [22][23]. However, T. viride

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• array of secondary metabolites, including sesquiterpenes [1][2][3][4][5][6][7], sesquiterpene-xanthones [8], diterpenes [9], sesterterpenes [10], cochlioquinones and peptides [11]. Moreover, several of these secondary metabolites are known to play important roles in mediating the virulence of these

• horizontal gene transfer [14]. To date, only three studies have explored phytotoxins from B. sorokiniana [2][7][10]. Therefore, in the framework of furthering our understanding of the roles of B. sorokiniana secondary metabolites in crop disease, we investigated the compounds produced by the ToxA-containing

• Cochliobolus sp.) [1][26], were reported in B. sorokiniana for the first time, while, known metabolites 6 and 7 [20], 9 [34], 11 [2], and 12 [16] were previously reported from B. sorokiniana (syn. C. sativus and H. sativum). The terpene synthase responsible for the biosynthesis of the sativene/longifolene

Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L.

• Annika Stein,
• Dave Compera,
• Bianka Karge,
• Mark Brönstrup and
• Jakob Franke

Beilstein J. Org. Chem. 2019, 15, 2003–2012, doi:10.3762/bjoc.15.196

• analysis revealed 4β-hydroxywithanolide E (1) as the major compound (50 mg) as well as the known metabolites withanolide E (4), withanolide F (5) and perulactone H (6) by comparison to literature data (Figure 1) [9][20]. Two additional compounds attracted our attention based on their unusual 1H NMR spectra

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• Sciences of the Czech Republic, Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i., 14220 Prague 4, Czech Republic 10.3762/bjoc.15.189 Abstract Sesquiterpene lactones are secondary plant metabolites with sundry

• anti-inflammatory activity of compound 1 using rat macrophages. Results and Discussion L. archangelica metabolite isolation and identification For isolation of the major metabolites of L. archangelica, we used 100 g of fine ground seeds (Supporting Information File 1, Figure S2) and the method of

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• from the involvement of sphingolipid metabolites in an array of important cell processes. ᴅ-threo-PDMP (1R,2R)-81 is a ceramide analogue identified as an inhibitor of glucosylceramide synthase (GCS) at micromolar concentrations [66][67]. It was efficiently synthesized [68][69] employing the alcohol (2R

Fluorine-containing substituents: metabolism of the α,α-difluoroethyl thioether motif

• Andrea Rodil,
• Alexandra M. Z. Slawin,
• Nawaf Al-Maharik,
• Ren Tomita and
• David O’Hagan

Beilstein J. Org. Chem. 2019, 15, 1441–1447, doi:10.3762/bjoc.15.144

• compounds that are of commercial significance [8][9][10]. Metabolism studies in both of these cases show that the major metabolites are their corresponding sulfoxides (Ar–S(O)CF3) and sulfones (Ar–S(O)2CF3) [8][9]. Indeed, in the case of the insecticide fipronil it is actually the sulfoxide (Ar–S(O)CF3

• , as they are less volatile, to avoid evaporation losses during extended incubations and work-up. Cultures of C. elegans were grown in Saboraud dextrose medium and incubated on an orbital shaker at 28 °C for 72 hours. New metabolites could be conveniently observed by extracting aliquots of the media

• into diethyl ether and dichloromethane (DCM) and then carrying out HPLC analyses. Incubation of thioether 4 with C. elegans led to the identification of three metabolites 6–8 as illustrated in Scheme 1. These were isolated by semi-preparative HPLC. Two of these (6 and 7) displayed an AB system in the

Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• the chemistry of the genus Massilia, in general. Because natural product-competent microorganisms typically synthesize multiple compounds [7], strain NR 4-1 appeared as a promising candidate to find further secondary metabolites. Further incentive for the chemical analysis of this bacterium came from

Phylogenomic analyses and distribution of terpene synthases among Streptomyces

• Lara Martín-Sánchez,
• Kumar Saurabh Singh,
• Mariana Avalos,
• Gilles P. van Wezel,
• Jeroen S. Dickschat and
• Paolina Garbeva

Beilstein J. Org. Chem. 2019, 15, 1181–1193, doi:10.3762/bjoc.15.115

• remarkable genetic potential to produce a large variety of secondary metabolites with different functions including antibiotics, antifungals, pigments or immunosuppressants [1][2][3]. These are compounds of diverse chemical nature such as polyketides, peptides, aminoglycosides or terpenoids [4][5

• ]. Terpenoids are the largest and the most diverse class of natural compounds known to date and include the initial products of terpene synthases and all derivatives made from them in tailoring steps. This very diverse class of organic compounds is best known as plant metabolites. However, recent studies

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• derivatives containing pyrrole and 2-aminoimidazole fragments in their structure were found among the metabolites of these marine organisms [1]. This group of compounds is characterized by an exceptional molecular diversity. The main structural types of these substances are shown in Figure 1. The metabolites

• recently from an extract of Pseudoceratina Sp. [6]. The variety of types of pharmacological activity revealed in these marine sponges’ metabolites is not inferior to the chemodiversity of their structure. Many of them are reported to have properties such as α-adrenoreceptors [7] and leukotriene B4 receptor

• metabolites of marine sponges with interesting biological properties has received considerable attention from both chemists and pharmacologists. In the middle of 2000s, the authors of the studies [17][18][19] proposed a facile one-pot two-step procedure for the synthesis of diversely substituted 2

New terpenoids from the fermentation broth of the edible mushroom Cyclocybe aegerita

• Frank Surup,
• Florian Hennicke,
• Nadine Sella,
• Maria Stroot,
• Steffen Bernecker,
• Sebastian Pfütze,
• Marc Stadler and
• Martin Rühl

Beilstein J. Org. Chem. 2019, 15, 1000–1007, doi:10.3762/bjoc.15.98

• ) is one of the most praised cultivated edible mushrooms and is being cultivated at large scale for food production. Furthermore, the fungus serves as a model organism to study fruiting body formation and the production of secondary metabolites during the life cycle of Basidiomycota. By studying the

• clusters. Keywords: bioinformatics; gene cluster analysis; natural products; secondary metabolites; structure elucidation; terpenes; Introduction The basidiomycete Agrocybe aegerita (synonym: A. cylindracea) was traditionally accommodated in the genus Agrocybe (family Bolbitiaceae) until a recent

• liquid culture and could eventually serve as hosts for heterologous production of secondary metabolites derived from other Basidiomycota that are more difficult or even impossible to culture. With these goals in mind, we have initiated extensive studies of the secondary metabolism of the aforementioned

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• transformations [1]. The cyclopropane subunit is also present in many biologically important compounds such as pheromones, fatty acid metabolites, unusual amino acids and possess interesting herbicidal, insecticidal, antibiotic, antibacterial, antifungal, antiviral and antitumor activities [2]. For these reasons

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• sesquiterpenoids and diterpenoids with various intriguing carbon skeletons, such as nardosinanes, neolemnanes, and ylanganes [10]. Many of these secondary metabolites have attracted a lot of attention for further synthetic and pharmacological studies due to their potent bioactivities ranging from neuroprotective

• , cytotoxic, to anti-inflammatory properties [10]. In the framework of our ongoing research for the bioactive metabolites from South China Sea soft corals [11][12], we made the collection of the title samples Clavularia viridis and Lemnalia flava off the Xisha Islands, Hainan Province, China. The chemical

• , eight sesquiterpenoids (1–8), belonging to four different structural types, were isolated from two South China Sea soft corals (C. viridis and L. flava) for the first time. The discovery of these metabolites extended the structural diversity and complexity of sesquiterpenoids derived from soft corals C

Synthesis of the aglycon of scorzodihydrostilbenes B and D

• Katja Weimann and
• Manfred Braun

Beilstein J. Org. Chem. 2019, 15, 610–616, doi:10.3762/bjoc.15.56

• multiple phenolic functionality. These natural products that form as secondary metabolites on a branch of flavonoid biosynthesis found wide interest for their various biological effects like anti-oxidative and biofouling-preventing activity [1]. From crude extracts of the Mongolian medicinal plant

Back to the future: Why we need enzymology to build a synthetic metabolism of the future

• Tobias J. Erb

Beilstein J. Org. Chem. 2019, 15, 551–557, doi:10.3762/bjoc.15.49

• avoided some problems upfront [58]. Yet, it needs to be mentioned that even if complex synthetic metabolic networks can be realized in vitro, this does not mean that these metabolic networks can be easily transplanted into living cells. The introduction of new reactions and metabolites into a host cell is

• expected to create interactions with the native metabolic and regulatory network of the host. Again, promiscuity poses a major challenge. Even though the metabolites and reactions might be completely non-native to the cell, these intermediates might be still drained due to unwanted side reactions or create

• there are likely to be hundreds if not thousands of unknown reactions and metabolites, often described as catalytic or metabolic “dark matter” [53][60]. Thus, a more detailed understanding of the promiscuity of native enzymes and the interaction of small molecules with the native regulatory network of

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• metabolites [16]. For example, Mycobacterium abscessus, which like P. aeruginosa and S. aureus can occur in the lung of cystic fibrosis patients [17][18][19], is able to methylate HQNO to give 2-heptyl-1-methoxy-4(1H)-quinolone (HMOQ). HMOQ is a significantly less efficient inhibitor of the respiratory chain

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• to antineurodegenerative activities [2][3]. The majority of natural coumarins are secondary metabolites isolated from plants [5][6][7]. A commonly used taxonomy for these natural products (which has been extended to the non-natural analogues) is based on the coumarin structure (Figure 1) [4][8]. It

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• mycotoxins [2], a class of highly bioactive secondary metabolites that belong to the strongest known inhibitors of protein biosynthesis in eukaryotes [3]. Similarly, the sesquiterpene aristolochene (2) is the parent hydrocarbon of PR toxin [4][5] and has been used as a marker to differentiate between toxin

• in secondary metabolites [20], but not much is known about volatiles from these fungi [21]. In continuation of this work, here we present the volatiles emitted by Hypoxylon griseobrunneum MUCL 53754 and Hypoxylon macrocarpum STMA 130423. These strains were selected, because both species released a

• ). Small amounts of matsutake alcohol (3) were also found. This volatile is frequently accompanied by other C8 metabolites [1], which is reflected for H. griseobrunneum by the detection of octan-3-one (8). Trace amounts of a series of alkylated pyrazines including methylpyrazine (9), 2,5-dimethylpyrazine

N-Acylated amino acid methyl esters from marine Roseobacter group bacteria

• Hilke Bruns,
• Lisa Ziesche,
• Nargis Khakin Taniwal,
• Laura Wolter,
• Thorsten Brinkhoff,
• Jennifer Herrmann,
• Rolf Müller and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 2964–2973, doi:10.3762/bjoc.14.276

• habitats with a broad metabolic potential [4][5][6][7]. Especially attached-living roseobacters produce diverse secondary metabolites, e.g., N-acylhomoserine lactones (AHLs) that the bacteria use for communication by quorum sensing [8][9][10]. AHLs are extensively investigated because of the broad

• them have been characterized so far [14][15][16][17][18]. Such signalling compounds as well as many other unknown metabolites often occur in small amounts, which renders trace detecting methods like GC/MS a suitable approach for their detection and structure elucidation, provided their polarity falls

• , interpretation of mass spectra, and verification by synthesis. Results and Discussion The secondary metabolites released by liquid cultures of various roseobacters were collected by extraction via Amberlite XAD-16 resin and analysed by GC/MS. Four of these strains, Roseovarius sp. D12_1.68 and Loktanella sp. F13

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• , PQS is produced through hydroxylation of position 3 by the NADH-dependent flavin mono-oxygenase PqsH [32]. This biosynthetic cascade is also responsible for the generation of the pqs-related metabolites DHQ, 2-AA, and HQNO as well as other AQs having different lengths of the alkyl chain [29][30

• (HIF-1) signaling pathways and, thus, down-regulate host innate immune systems [36][37]. Other PQS-related metabolites have been shown to have additional effects. HQNO, for example, induces autolysis and release of extracellular DNA thereby promoting biofilm formation and increasing meropenem tolerance

• in combination with sub-therapeutic doses of ciprofloxacin. In an analytics-driven study by Allegretta et al., the compound was further profiled regarding suppression of the PQS-related metabolites DHQ, 2-AA, HHQ, PQS and HQNO. In brief, this study demonstrated that PqsR is an excellent target for

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• h) with lysosomal homogenate, leading to the formation of various peptide fragments and Dau-containing metabolites such as H-Lys(Dau=Aoa)-OH [17][19][35]. LC–MS spectra recorded during the lysosomal degradation studies could also indicate the cleavage of an amide bond between the side chain of 4Lys

• and the fatty acids [19]. This result suggests that besides the Dau-metabolites the fatty acids could also be released and – as second drugs – could contribute to the tumor growth inhibitory action of conjugates. It is assumed that the higher short-term cytotoxic activity of [4Lys(Bu)]-GnRH-III(Dau

• caspase-3 [39]. It is possible that the Dau-metabolites formed inside the cells need longer time to exert their more prominent antitumor effect, which could explain why the long-term cytotoxic effect was almost the same for the two acylated conjugates. It has been reported that doxorubicin (an analog of

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• of spinosyns via chemical modification [18]. Bioactivities of many microbial secondary metabolites are highly dependent on their sugar constituents which are transferred as nucleotide-activated sugars to an aglycon by glycosyltransferases [19]. Therefore, bioactivities of these metabolites could

• . Particularly, the compound 8b was approximately as active as spinosad. Carbohydrate substituents are considered to be related closely to many secondary metabolites [19], hence, C17–O glycosyl analogues are regarded as efficient insecticides that are likely to rival present insecticides. However, as noted in