Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• natural metabolites available from plants, phenolic compounds play a particularly important role in human health as they occur in significant amounts in many fruits, vegetables and medicinal plants. In this review natural phenolic compounds of plant origin with significant anti-angiogenic properties are

• options with antibodies and VEGF receptor inhibitors showed several clinical limitations, making the search for further clinically relevant targets and other drugs necessary to combat tumor-related angiogenesis. Secondary natural metabolites have also been identified as attractive candidates for the

• polyphenols was previously considered as unspecific, more recently, observations of a specific interference with biological mechanisms at the molecular level have significantly increased. Especially in the fields of anti-inflammatory activity, chemoprevention and cytoprotection, natural phenolic metabolites

Cathodic reductive coupling of methyl cinnamate on boron-doped diamond electrodes and synthesis of new neolignan-type products

• Taiki Kojima,
• Rika Obata,
• Tsuyoshi Saito,
• Yasuaki Einaga and
• Shigeru Nishiyama

Beilstein J. Org. Chem. 2015, 11, 200–203, doi:10.3762/bjoc.11.21

• -type products were synthesized from the hydrodimer. Keywords: boron-doped diamond (BDD) electrode; cathodic reduction; electrochemistry; electrosynthesis; neolignan; Introduction Numerous lignans and neolignans were found as secondary plant metabolites, and many of them are known to exhibit

A carbohydrate approach for the formal total synthesis of (−)-aspergillide C

• Pabbaraja Srihari,
• Namballa Hari Krishna,
• Ydhyam Sridhar and
• Ahmed Kamal

Beilstein J. Org. Chem. 2014, 10, 3122–3126, doi:10.3762/bjoc.10.329

• rings) are unexpected, novel, secondary metabolites, isolated from the marine-derived fungus Aspergillus ostianus strain 01F313 in bromine-modified 1/2PD culture medium [1][2][3][4]. Interestingly, these compounds show cytotoxicity against mouse lymphocytic leukemia cells (L1210) with LD50 values of 2.1

Trogopterins A–C: Three new neolignans from feces of Trogopterus xanthipes

• Soyoon Baek,
• Xuikui Xia,
• Byung Sun Min,
• Chanil Park and
• Sang Hee Shim

Beilstein J. Org. Chem. 2014, 10, 2955–2962, doi:10.3762/bjoc.10.313

• with IC50 values of 34.77–45.68 μM. Keywords: cytotoxic activity; neolignans; Trogopterus xanthipes; Introduction Chemical studies of natural products including ones derived from plants and microorganisms have led to the isolation of numerous novel metabolites with biological activities [1][2]. As a

Thermal and oxidative stability of the Ocimum basilicum L. essential oil/β-cyclodextrin supramolecular system

• Daniel I. Hădărugă,
• Nicoleta G. Hădărugă,
• Corina I. Costescu,
• Ioan David and
• Alexandra T. Gruia

Beilstein J. Org. Chem. 2014, 10, 2809–2820, doi:10.3762/bjoc.10.298

• to these aspects, such as diepoxidation of limonene to the carcinogenic diepoxylimonene or oxidation of other terpenes (e.g., pinene) to harmful oxidized derivatives [14][26][27], the degradation of safrole to carcinogenic metabolites [28], or the formation of oxygentated derivatives of limonene

Binding mode and free energy prediction of fisetin/β-cyclodextrin inclusion complexes

• Bodee Nutho,
• Wasinee Khuntawee,
• Chompoonut Rungnim,
• Piamsook Pongsawasdi,
• Peter Wolschann,
• Alfred Karpfen,
• Nawee Kungwan and
• Thanyada Rungrotmongkol

Beilstein J. Org. Chem. 2014, 10, 2789–2799, doi:10.3762/bjoc.10.296

• ; Introduction Flavonoids are polyphenolic compounds which are found in many plants as well as in several microorganisms [1][2]. They are herbal secondary metabolites with a wide range of biological and pharmacological activities and are used as therapeutic drugs having many benefits for protection and medical

Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3

• Zhi Kai Guo,
• Rong Wang,
• Wei Huang,
• Xiao Nian Li,
• Rong Jiang,
• Ren Xiang Tan and
• Hui Ming Ge

Beilstein J. Org. Chem. 2014, 10, 2677–2682, doi:10.3762/bjoc.10.282

• to be a rich source of bioactive natural compounds [1][2]. Recently, a wide variety of biologically active and structurally unique metabolites were isolated from these types of microorganisms [3][4][5][6], demonstrating their promise as a source of novel and/or bioactive natural products. Our

• previous chemical investigation of the bioactive secondary metabolites produced by the endophytic Aspergillus sp. YXf3 associated with Ginkgo biloba led to the isolation of new p-terphenyls and novel types of diterpenoids including pimarane-type diterpenoids (sphaeropsidins A and B, aspergiloids D and E

• investigation of Aspergillus sp. YXf3 revealed it is a pluripotent fungus which can produce different types of novel interesting metabolites, including p-terphenyls, pimarane, cleistanthane, norcleistanthane-type diterpenoids [7], and the “aspergilane”-type norditerpenoid 1. It is possible to propose that 1 is

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• bioactive metabolites and selective labeling of proteins and other biomacromolecules. A common structural motif for such probes consists of a reporter that can be attached by copper(I)-catalyzed 1,2,3-triazole formation between terminal alkynes and azides to a reactive headgroup. Here we introduce the

• enables identification of tagged analytes even in complex samples. Introduction of bromine substituents does not only affect the isotopic pattern of analytes but also increases ionization and the detection limit of small metabolites [36] and peptides [37]. In addition, introduction of Br or Cl by labeling

Effect of cyclodextrin complexation on phenylpropanoids’ solubility and antioxidant activity

• Miriana Kfoury,
• David Landy,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2014, 10, 2322–2331, doi:10.3762/bjoc.10.241

• , cinnamon, etc). PPs play a vital role in plants integrity and defense against biotic or abiotic stresses and are considered as “secondary metabolites” [1]. They are divided in several major classes such as coumarins, flavonoids, phenylpropenes and hydroxycinnamic acids [2]. PPs have an important

Photochemical approach to functionalized benzobicyclo[3.2.1]octene structures via fused oxazoline derivatives from 4- and 5-(o-vinylstyryl)oxazoles

• Ivana Šagud,
• Simona Božić,
• Željko Marinić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2014, 10, 2222–2229, doi:10.3762/bjoc.10.230

• framework of numerous important biologically active natural compounds or their metabolites [1]. Properly functionalized bicyclo[3.2.1]octanes have proved as useful reactive intermediates in stereoselective transformations making these derivatives powerful building blocks in organic synthetic strategies [2

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• substituted 2,5-dioxabicyclo[2.2.1]heptane and 2,6-dioxabicyclo[3.2.1]octane rings. Such substituted bicyclic rings are of further interest as they are the core substructures in a number of marine derived metabolites, including ocellenynes and sorangicin A. Results and Discussion Synthesis of starting

Sacrolide A, a new antimicrobial and cytotoxic oxylipin macrolide from the edible cyanobacterium Aphanothece sacrum

• Naoya Oku,
• Miyako Matsumoto,
• Kohsuke Yonejima,
• Keijiroh Tansei and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2014, 10, 1808–1816, doi:10.3762/bjoc.10.190

• restaurants or for personal consumption. Keywords: Aphanothece sacrum; cyanobacterium; food intoxication; natural products; sacrolide A; suizenji-nori; Introduction Cyanobacteria continue to be core sources for bioactive secondary metabolites [1][2], and their significance in drug discovery has increased

• metabolites were found from corn [17][18]. However, they comprise a pair of enantiomers and thus should be generated non-enzymatically from α-linoleic acid-derived allene oxide. In contrast, 1 is optically active and is more likely to be produced by a sequence of enzymatic reactions. Sacrolide A (1) inhibited

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• . Keywords: headspace analysis; natural products; polyketide biosynthesis; pyridine derivatives; streptazolin; volatile compounds; Introduction Actinomycetes are excellent producers of diverse and bioactive secondary metabolites. These metabolites belong to many different structural classes including

• the production of other, usually less volatile secondary metabolites and whether different compounds can be detected by headspace analysis [7] compared to commonly used solvent extraction or adsorption/extraction procedures. Strain FORM5 has been reported to produce the tetrahydrocyclopenta[b]pyridine

• structure verification. Agar plate cultures and liquid cultures were investigated and the liquid phase analyzed for the presence of secondary metabolites. The results showed that by headspace analysis new secondary metabolites can be found that eluded earlier analysis. The separate analysis of headspace and

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

• Fabrizio Chiodo,
• Marco Marradi,
• Javier Calvo,
• Eloisa Yuste and
• Soledad Penadés

Beilstein J. Org. Chem. 2014, 10, 1339–1346, doi:10.3762/bjoc.10.136

• triphosphorylated to active metabolites that can compete with the natural substrate of RT avoiding the RNA retrotranscription, e.g., the viral replication. Abacavir and lamivudine (being NRTi) inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator in DNA synthesis. The lack of a 3

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• ; stereoselective amine synthesis; triol synthesis; Introduction 7-Deazapurine (pyrrolo[2,3-d]pyrimidine) nucleosides are commonly found in nature playing a variety of roles such as building blocks of nucleic acids and tRNA, metabolites or antimetabolites [1]. Deazapurine ribonucleosides also show interesting

Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery

• Jens Schmidt,
• Zeinab Khalil,
• Robert J. Capon and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2014, 10, 1228–1232, doi:10.3762/bjoc.10.121

• sesquiterpenyl subunit in heronapyrroles A–C provoked the hypothesis that there might exist other hitherto unidentified metabolites. On biosynthetic grounds a mono-tetrahydrofuran-diol named heronapyrrole D appeared a possible candidate. We here describe a short asymmetric synthesis of heronapyrrole D, its

4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions

• Michael J. Burns,
• Thomas O. Ronson,
• Richard J. K. Taylor and
• Ian J. S. Fairlamb

Beilstein J. Org. Chem. 2014, 10, 1159–1165, doi:10.3762/bjoc.10.116

• phacelocarpus 2-pyrones 1 and 2 (Figure 1). These compounds are secondary metabolites isolated from the Australian marine red alga Phacelocarpus labillardieri [5]; similar compounds from the same family have been shown to exhibit phospholipase A2 (PLA2) inhibitory activity [6]. Whilst the chemistry of 2-pyrones

Synthesis of zearalenone-16-β,D-glucoside and zearalenone-16-sulfate: A tale of protecting resorcylic acid lactones for regiocontrolled conjugation

• Hannes Mikula,
• Julia Weber,
• Dennis Svatunek,
• Philipp Skrinjar,
• Gerhard Adam,
• Rudolf Krska,
• Christian Hametner and
• Johannes Fröhlich

Beilstein J. Org. Chem. 2014, 10, 1129–1134, doi:10.3762/bjoc.10.112

• natural product conjugates. Keywords: glycosylation; masked mycotoxins; resorcylic acid esters; sulfation; zearalenone; Introduction Resorcylic acid lactones (RALs, Figure 1), a compound class of benzannulated macrolides, are pharmacologically active secondary metabolites produced by a variety of

• glycosylation has been reported by Grabley et al. [14]. ZEN-14-sulfate (6, Figure 2A) was first isolated from F. graminearum-inoculated rice [15] and both, the glucoside 5 and the sulfate 6, were identified as ZEN metabolites in Arabidopsis thaliana [16]. These conjugates are easily hydrolyzed back to the

• 8 in reasonable amounts for ongoing research and further investigations in the field of conjugated/masked mycotoxins. Structure of selected RAL type fungal secondary metabolites. Structures of zearalenone conjugates: (A) ZEN-14-β,D-glucoside (5) and ZEN-14-sulfate (6), (B) ZEN-16-β,D-glucoside (7

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• ., through molecular recognition of a preferred binding site [2][3][4][5], thereby ensuring the selectivity of a chemotherapeutic agent. Particularly common are side chains composed of deoxygenated sugars [6]. For example, the kigamicins are bacterial secondary metabolites isolated from Amicolatopsis sp. [7

Cuevaenes C–E: Three new triene carboxylic derivatives from Streptomyces sp. LZ35ΔgdmAI

• Jing-Jing Deng,
• Chun-Hua Lu,
• Yao-Yao Li,
• Shan-Ren Li and
• Yue-Mao Shen

Beilstein J. Org. Chem. 2014, 10, 858–862, doi:10.3762/bjoc.10.82

• A and B (1 and 2) from the metabolites of the strain LZ35ΔgdmAI (Figure 1). The antimicrobial activities of cuevaenes A–E (1–5) were evaluated. Results and Discussion The strain Streptomyces sp. LZ35ΔgdmAI was cultured on oatmeal medium for 11 days at 28 °C and extracted with EtOAc/MeOH/AcOH (80:15

New sesquiterpene hydroquinones from the Caribbean sponge Aka coralliphagum

• Qun Göthel and
• Matthias Köck

Beilstein J. Org. Chem. 2014, 10, 613–621, doi:10.3762/bjoc.10.52

• viscous mucus containing the toxic secondary metabolites which are produced by the sponge tissue [3]. This ecological observation inspired the chemical investigation of this sponge by different research groups. Thus many secondary metabolites have been reported, such as the sesquiterpene phenolic

• halenaquinol sulfate from the marine sponge Xestospongia sapra [14]. In the course of our investigation on the sponge Aka coralliphagum, we isolated a number of compounds containing sulfated phenols. These sulfated metabolites are labile [5], and easily loose the sulfate ester groups by hydrolysis in water [15

• sulfated form and their activities get increased by hydrolysis of these labile groups. This would lead to a prolonged bioactivity of these metabolites and therefore to a more efficient defense against predators or pathogens. Experimental 1H and 13C NMR spectra were recorded on a Bruker Avance 600 MHz NMR

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• the cellular uptake of modified biosynthetic intermediates. Processing of these intermediates, sometimes called mutasynthons, can provide complex secondary metabolites specifically modified as planned by choice of the synthetic modification incorporated into the mutasynthon [5][6][7]. In earlier work

• , we demonstrated that the ansamitocins (maytansinoids) 3–5 are an ideal showcase for creating small libraries by mutasynthesis [8][9][10]. These secondary metabolites exert strong antiproliferative activity towards different leukemia cell lines as well as human solid tumors. Inhibitory concentrations

• ). From here a set of tailoring enzymes transform proansamitocin into the bioactive final metabolites 3–5 following a predetermined logic that is only flexible in part (Scheme 1). We extended these studies by combining mutasynthesis and semisynthesis and thus accessed four new tumor specific folic acid

An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

• Suresh Babu Meruva,
• Akula Raghunadh,
• Raghavendra Rao Kamaraju,
• U. K. Syam Kumar and
• P. K. Dubey

Beilstein J. Org. Chem. 2014, 10, 471–480, doi:10.3762/bjoc.10.45

• Heonjoong et al. isolated new β-carboline-based metabolites, designated as eudistomins Y1−Y7 (6a–g) [12][13][14] (Figure 1), from the tunicate of the genus Eudistoma and posses a benzoyl group at the C-1 position of the β-carboline structural framework. Eudistomins Y1−Y7 (6a–6g) were evaluated for their

Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• extract to remove the large excess of oil before HPLC purification. Analysis by LC–MS revealed that the predicted monensin-related metabolites were indeed produced at elevated levels (see typical results in Figure 1 and Table 1) compared to monensin production in the wild type strain, on either SM-16 or

• action. It remains to be established whether the sodium cation is recruited into the ACP-bound polyether even before monensin is released. Meanwhile, the convenient production of large amounts of advanced monensin-related metabolites by an engineered industrial strain now opens the way to the synthesis

• conditions: Monensin (1) and the related metabolites 3, 4 and 5 were produced as follows: 25 mL germination medium (soya flour (15.0 g L−1), dry yeast (1.5 g L−1), glucose (5 g L−1), dextrin (20 g L−1), CaCO3 (1 g L−1), pH 6.4) were inoculated with either S. cinnamonensis overproducer strain A519 or a mutant

Tanzawaic acids I–L: Four new polyketides from Penicillium sp. IBWF104-06

• Louis P. Sandjo,
• Eckhard Thines,
• Till Opatz and
• Anja Schüffler

Beilstein J. Org. Chem. 2014, 10, 251–258, doi:10.3762/bjoc.10.20

• Hz)/δC 144.8. Moreover, these spectra showed signals of three CH3 groups, two CH2 groups, six CH groups, and two quaternary carbons (Table 1 and Table 2). These data suggested a structural similarity of 1 to the tanzawaic acids, secondary metabolites from Penicillium citrinum [1]. COSY and HMBC

• secondary metabolites to the aforementioned strains which do belong to the Penicillium section Citrina [6]. Tanzawaic acid E differs from tanzawaic acid L by two more hydrogen atoms at C-6 and C-15 and has the same elemental composition as tanzawaic acid K, the structural difference being the position of