A new and efficient procedure for the synthesis of hexahydropyrimidine-fused 1,4-naphthoquinones

• Marcelo Isidoro P. Reis,
• Vinícius R. Campos,
• Jackson A. L. C. Resende,
• Fernando C. Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2015, 11, 1235–1240, doi:10.3762/bjoc.11.137

• ]quinazoline; microwave; naphthoquinone; 1,3-quinazoline; 1,3,5-triazinane; Introduction Quinones represent a diverse family of naturally occurring secondary metabolites [1][2][3]. Interest in these substances has intensified in recent years due to their pharmacological importance [4]. Heterocycle-fused

Synthesis of the furo[2,3-b]chromene ring system of hyperaspindols A and B

• Danielle L. Paterson and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 265–270, doi:10.3762/bjoc.11.29

• hepatitis and depression, and as topical antimicrobials for wounds and snake bites [2][3][4][5]. There is great interest in secondary metabolites produced by plants from the Hypericum genus due to the bioactivity of many compounds that have been isolated from this source. A wide variety of compounds have

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

• cells (HMEC-1) have been given special attention. In contrast, compounds showing in vitro anti-angiogenic activity but also signs of strong unspecific cytotoxic effects in vitro have been excluded. The secondary metabolites discussed include six flavonoids from different subclasses: quercetin, fisetin

• acts to suppress the signaling pathways mediated by VEGFR2, inducing apoptosis in endothelial cells. Quinoline-substituted phenols To date, quinolone-substituted phenols (Qsps) have not been reported as natural secondary metabolites, although quinolone and alkylated phenols are common structural

• basic condition. 4-Amino-2-sulfanylphenol derivatives The class of 4-amino-2-sulfanylphenols is obviously an outlier among the reviewed compounds, as the 2-sulfanylphenol substructure is not a structural element in natural products. The vast majority of thiol groups in secondary metabolites derive from

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

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

• 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

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

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

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

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

• 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

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

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

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

The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via three-component reactions of acrylamides and aroylacrylic acids with isatins and α-amino acids

• Tatyana L. Pavlovskaya,
• Fedor G. Yaremenko,
• Victoria V. Lipson,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Vladimir I. Musatov and
• Alexander S. Karpenko

Beilstein J. Org. Chem. 2014, 10, 117–126, doi:10.3762/bjoc.10.8

• commutatа [4], mitraphylline from Uncaria tomentosa [5] and spirotryprostatines A and B from the secondary metabolites of Aspergillus fumigatus [6][7][8]. In particular, oxindole derivatives are well known as powerful anti-tumor agents due to their kinase inhibitory properties, especially as tyrosine kinase

Plakilactones G and H from a marine sponge. Stereochemical determination of highly flexible systems by quantitative NMR-derived interproton distances combined with quantum mechanical calculations of ¹³C chemical shifts

• Simone Di Micco,
• Angela Zampella,
• Maria Valeria D’Auria,
• Carmen Festa,
• Simona De Marino,
• Raffaele Riccio,
• Craig P. Butts and
• Giuseppe Bifulco

Beilstein J. Org. Chem. 2013, 9, 2940–2949, doi:10.3762/bjoc.9.331

• to the huge chemical variety of secondary metabolites from natural sources, the identification of the configuration of highly flexible compounds is still a great challenge. We recently demonstrated that an integrated approach combining quantitative NOE-based protocol in parallel with the quantum

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• secondary metabolites and the characterization of their influence on survivin expression, we employed a human survivin-promoter dependent transcriptional reporter in the transiently transfected human colorectal carcinoma cell line Colo 320. Due to the overexpression of survivin in many human cancers

[²H₂₆]-1-epi-Cubenol, a completely deuterated natural product from Streptomyces griseus

• Christian A. Citron and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 2841–2845, doi:10.3762/bjoc.9.319

• the homomonoterpene 1 proceeds by S-adenosylmethionine-dependent methylation of GPP followed by a cyclisation reaction [3][4][5]. For biosynthetic studies on secondary metabolites isotopically labelled precursors are frequently used. Historically, the usage of radiolabelled compounds was most

Halogenated volatiles from the fungus Geniculosporium and the actinomycete Streptomyces chartreusis

• Tao Wang,
• Patrick Rabe,
• Christian A. Citron and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 2767–2777, doi:10.3762/bjoc.9.311

• , but the overall trend is similar, and therefore chlorine and bromine are also the most widespread halogens in natural products from terrestrial organisms. Many biologically active halogenated secondary metabolites are known from actinomycetes including vancomycin [4], chloramphenicol [5], rebeccamycin

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• cosmic dissymmetry.“ [1] - Louis Pasteur These visionary words were written over 100 years ago by Louis Pasteur. Little did he know how great of a challenge underlies these words. Natural products, secondary metabolites produced by living organisms, have their own distinct structures. Some of them have

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• chemical companies in recent years, natural products continue to serve as one of the most important sources of new bioactive chemical entities, both in the pharmaceutical [1][2][3][4] as well as in the agrochemical industry [5][6][7][8]. A particularly rich source of intriguing secondary metabolites with

• . Comparison of UV and molecular mass data of these secondary metabolites with an in-house compound library resulted in no hits, thus prompting us to their isolation and structural elucidation. The UV spectrum of 7 revealed maxima at 218 and 286 nm, strongly suggesting the presence of an aromatic system within

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• biosynthetic pathway. Keywords: antimycins; gene regulation; genome mining; natural products; Streptomyces; Review It is estimated that around 60% of all known antibiotics are derived from secondary metabolites made by filamentous actinomycete bacteria, most notably Streptomyces species [1]. Streptomyces

• unigenomic spores [2]. Aerial hyphae production and sporulation is triggered by nutritional stress and is accompanied by the production of secondary metabolites. These specialised metabolites likely function both as chemical weapons against competing organisms in the soil and as signaling molecules to

• albicans (Seipke and Hutchings, unpublished results), but the exact time in which AntO installs the N-formyl group is unclear and requires investigation. Regulation of the ant gene cluster Antimycin biosynthesis is linked to development, as is the case for many Streptomyces secondary metabolites. However

Activation of cryptic metabolite production through gene disruption: Dimethyl furan-2,4-dicarboxylate produced by Streptomyces sahachiroi

• Dinesh Simkhada,
• Huitu Zhang,
• Shogo Mori,
• Howard Williams and
• Coran M. H. Watanabe

Beilstein J. Org. Chem. 2013, 9, 1768–1773, doi:10.3762/bjoc.9.205

• knockout may constitute a means to “activate” the production of novel secondary metabolites that would otherwise lay dormant within microbial genome sequences. Keywords: cryptic metabolite; dimethyl furan-2,4-dicarboxylate; genetic knockout; natural products; non-ribosomal peptide synthetase module

• ]. The gene encodes a NRPS (non-ribosomal peptide synthetase, an enzyme involved in the biosynthesis of various peptide containing secondary metabolites) module of unusual domain architecture consisting of condensation, peptidyl carrier protein, and condensation domains (C-PCP-C), respectively. Gene

• was carried out following standard procedures [21] with a radioactive 32P-ATP labeled probe. The probe was generated through PCR amplification using the aziA2 probe-F/aziA2 Probe R set of primers and following the same PCR condition as detailed above. Fermentation and analysis of secondary metabolites

New tridecapeptides of the theonellapeptolide family from the Indonesian sponge Theonella swinhoei

• Annamaria Sinisi,
• Barbara Calcinai,
• Carlo Cerrano,
• Henny A. Dien,
• Angela Zampella,
• Claudio D’Amore,
• Barbara Renga,
• Stefano Fiorucci and
• Orazio Taglialatela-Scafati

Beilstein J. Org. Chem. 2013, 9, 1643–1651, doi:10.3762/bjoc.9.188

• treasure troves of secondary metabolites. The chemical diversity of the isolated compounds ranges from unusual steroids (exemplified by the 4-methylene sterol theonellasterol [2][3] and truncated side-chain sulfated steroids [4]), to complex macrocyclic polyketides (as the well-known swinholide A, now a

• reference compound in the class of actin interacting cell growth inhibitors [5]), polyene derivatives (as aurantosides [6]), and polypeptides/depsipeptides. The biosynthesis of several secondary metabolites of Theonella has been ascribed to symbiotic microorganisms, as in the case of the polyketide onnamide

• [7] and the polypeptide polytheonamide [8]. It is, however, not unreasonable to presume that a symbiotic role in the production of secondary metabolites could be crucial in many other cases. Probably the most distinctive class of secondary metabolites of Theonella is given by complex polypeptides