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

• , a precooking treatment to manually deactivate 1 was desired. We hypothesized that the modification of the reactive enone functionality or the degradation of the cyclic structure may eliminate the bioactivity of 1, and envisioned that the treatment with an alkaline solution may serve this purpose. In

Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

• Patrick Rabe,
• Tim A. Klapschinski,
• Nelson L. Brock,
• Christian A. Citron,
• Paul D’Alvise,
• Lone Gram and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2014, 10, 1796–1801, doi:10.3762/bjoc.10.188

• several structural analogues of TDA and used them in bioactivity tests against Staphylococcus aureus and Vibrio anguillarum for a structure–activity relationship (SAR) study, revealing that the sulfur-free analogue of TDA, tropone-2-carboxylic acid, has an antibiotic activity that is even stronger than

• the bioactivity of the natural product. The synthesis of this compound and of several analogues is presented and the bioactivity of the synthetic compounds is discussed. Keywords: antibiotics; natural products; Roseobacter; SAR study; tropodithietic acid; tropone; Introduction Tropodithietic acid

• , suggesting that TDA may interact with several targets [13]. Here we report on the synthesis and bioactivity of several TDA analogues for investigating the structure–activity relationship (SAR) of this unique marine antibiotic. Results and Discussion Synthesis of analogues of tropodithietic acid For a

Chemistry of polyhalogenated nitrobutadienes, 14: Efficient synthesis of functionalized (Z)-2-allylidenethiazolidin-4-ones

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Mimoza Gjikaj and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2014, 10, 1638–1644, doi:10.3762/bjoc.10.170

• describe the formation of uniquely substituted thiazolidin-4-ones, a class of compounds which has proven to exhibit distinctive bioactivity, e.g., antifungal, antibacterial, antitubercular, and anticonvulsant properties [18][19][20][21][22][23][24][25][26][27][28]. Additionally, more recent studies often

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• receptors [5]. In particular, 3,3-disubstituted 3-amino-2-oxindoles are present in several drug candidates. They exhibit various types of bioactivity, such as the potent gastrin/CCK-B receptor antagonist I [6], the vasopressin VIb receptor antagonist II [7][8], the CRTH2 (DP2) receptor antagonist

Tailoring of organic dyes with oxidoreductive compounds to obtain photocyclic radical generator systems exhibiting photocatalytic behavior

• Christian Ley,
• Julien Christmann,
• Ahmad Ibrahim,
• Luciano H. Di Stefano and
• Xavier Allonas

Beilstein J. Org. Chem. 2014, 10, 936–947, doi:10.3762/bjoc.10.92

• of this research area, the development of photoradical generators (PRG) is still a lively topic that finds applications in triggering bioactivity [1], drug or fragrance release [2][3][4], microelectronics [5], water catalysis reduction [6][7][8], and laser imaging [9]. In organic chemistry, the

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

• microbes at 30 μg/disc, indicating that the existence of the carboxyl group (1-COOH) is essential for the bioactivity. Previously, Liu et al. [7] reported the synthesis of cuevaene A. However, the NMR spectroscopic data of cuevaene A failed to match the published data. In a later paper, Taylor et al. [6

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

• aqueous n-BuOH extract yielded the new compounds siphonodictyals E1–E4 (1–4) and cyclosiphonodictyol A (5). In this article, we describe the isolation, structural elucidation, and bioactivity of compounds 1–5 from the Aka growth form incrustans, as well as discuss the biosynthetic pathway of related

• ]. Moreover, the influence of the sulfate esters on the bioactivity has been proven by activity tests: the desulfated compounds tend to be more active [5]. Therefore, we propose that the sulfate esters act as hydroxy protecting groups. The sponges excrete the sesquiterpene hydroquinones primarily in the

• 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

• introduce a thiol linker by Huisgen-type cycloaddition which can principally be utilized to create tumor targeting conjugates. In bioactivity tests, only those new ansamitocin derivatives showed strong antiproliferative activity that bear an ester side chain at C-3. Keywords: ansamitocins; antibiotics

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

• Magnaporthe oryzae, one of the most devastating plant diseases on cultivated rice. Bioactivity-guided fractionation of organic extracts led to the isolation of a series of eight pure compounds, the structures of which were elucidated by 2D NMR spectroscopy as well as by mass spectrometry. Results and

• . The isolated compounds were tested for their bioactivity in a series of antimicrobial and antiproliferative assays. We found that apart from compounds 1 and 2, the other isolates (3–8) inhibited the conidial germination in Magnaporthe oryzae at concentrations of 50 µg/mL or less (Table 3) whereas the

• addition, tanzawaic acid A (7) showed weak activity in agar diffusion assays at 50 µg/filter dics against Bacillus brevis, Mucor miehei, and Paecilomyces variotii, as well as cytotoxic effects against HeLaS3 cells at a concentration of 50 µg/mL. However, none of the other compounds showed bioactivity in

Charge-transfer interaction mediated organogels from 18β-glycyrrhetinic acid appended pyrene

• Jun Hu,
• Jindan Wu,
• Qian Wang and
• Yong Ju

Beilstein J. Org. Chem. 2013, 9, 2877–2885, doi:10.3762/bjoc.9.324

• the form of free acids or aglycones, has been noted by its low toxicity, biocompatibility and bioactivity [31][32]. A wide array of papers has been published to report its anti-inflammatory, antiviral, and antitumor effects [33][34]. In recent years, it has been found that triterpenoids can serve as

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

• the culture fluid in the survivin promoter dependent reporter gene assay as described below. The compounds were isolated from the culture fluid by bioactivity-guided fractionation using the survivin transcriptional reporter assay in Colo 320 cells. The fermentation was stopped after 18 days, when the

• (60:40) as eluent to yield 28 mg of SF002-96-1 (tR: 13 min). During bioactivity-guided fractionation and isolation of compound SF002-96-1, no other compounds have been detected inhibiting survivin promoter activity. The purity of the isolated compound was analyzed with a Hewlett-Packard Series 1100LC

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

• utilise acyl-SNACs provides the possibility to employ feeding studies to introduce new chemistry at C-8. AntO is a lipase homologue and is predicted to install the N-formyl group resulting in the 3-formamidosalicylate moiety. AntO is required for bioactivity against the human pathogenic fungus, Candida

• bioactivity of 5-fluoroantimycins and reported they retained potent antifungal activity against Candida albicans, but were significantly reduced in cytotoxity in a leukemia P388 mouse cell line compared to the parent compounds [25]. Sandy et al. recently showed AntB can accept both acyl-CoAs and acyl-SNACs to

Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

• Johann Moschner,
• Anna Chentsova,
• Nicole Eilert,
• Irene Rovardi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2013, 9, 2328–2335, doi:10.3762/bjoc.9.267

• cells. An extension of this study to F-ring-modified structures shows the necessity of a rigidly positioned nitrogen atom for bioactivity as well as the presence of the C21 methyl group for acid stability and bioactivity. Keywords: cyclopamine; hedgehog signaling pathway; natural products; steroidal

• and 9 it becomes evident that the F-ring is necessary for bioactivity. The piperidine moiety provides a rather rigidly placed nitrogen atom. Nevertheless, a pyrrolidine as in compound 23 still provides the correct orientation of the nitrogen atom. Despite compounds 8 and 9 being inactive in the assay

• , both derivatives induced cytotoxicity in the concentration range tested. Very subtle changes of the conformation of the piperidine ring significantly change bioactivity: While 25-epi-exo-cyclopamine 5 shows reduced activity in comparison to exo-cyclopamine 2, bis-exo-cyclopamine 6 is the most active

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• -cleavable complex they prevent the replication of DNA and act as efficient antitumor compounds [21]. The extraordinary bioactivity of indolocarbazoles has drawn a lot of attention from chemists and biologists. The biosynthesis of staurosporine (26) and rebeccamycin (28), both being the most prominent

Synthesis and antibacterial activity of monocyclic 3-carboxamide tetramic acids

• Yong-Chul Jeong and
• Mark G. Moloney

Beilstein J. Org. Chem. 2013, 9, 1899–1906, doi:10.3762/bjoc.9.224

• found that 3-alkoxycarbonyl and 3-carboxamide tetramic acids prefer tautomer A, while the preference of 3-acyltetramic acids depends on the N(1)-functionality. Of particular interest is that 3-carboxamide analogues, especially 2b, have shown bioactivity against various Gram-positive bacteria including

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

• aliphatic amino acids; ii) the abundance of N-methylated residues and iii) the presence of a macrocycle made up by more than ten amino acids. Only a few theonellapeptolides have been tested for immunosuppressive activity and they revealed a moderate potency [25]. In general, the potential bioactivity of

ML212: A small-molecule probe for investigating fluconazole resistance mechanisms in Candida albicans

• Willmen Youngsaye,
• Cathy L. Hartland,
• Barbara J. Morgan,
• Amal Ting,
• Partha P. Nag,
• Benjamin Vincent,
• Carrie A. Mosher,
• Joshua A. Bittker,
• Sivaraman Dandapani,
• Michelle Palmer,
• Luke Whitesell,
• Susan Lindquist,
• Stuart L. Schreiber and
• Benito Munoz

Beilstein J. Org. Chem. 2013, 9, 1501–1507, doi:10.3762/bjoc.9.171

• fungal cells. A substituted indazole possessing the desired bioactivity profile was selected for further development, and initial investigation of structure–activity relationships led to the discovery of ML212. Keywords: antifungal; Candida albicans; chemosensitizer; fluconazole; Molecular Libraries

• . While bioactivity is still observed with these substances, they all appear to be only weakly active (IC50 = 2–8 μM). Conversely, the meta-substituted systems 35–38 prove to be the most conducive to potency. The methyl ether 36 is potent against CaCi-2 (IC50 = 0.7 μM) as is the N,N-dimethylamine variant

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

• Brad M. Loertscher,
• Yu Zhang and
• Steven L. Castle

Beilstein J. Org. Chem. 2013, 9, 1179–1184, doi:10.3762/bjoc.9.132

• addition to its interesting bioactivity, lyconadin A presents a significant synthetic challenge by virtue of its unique pentacyclic skeleton, which contains six stereocenters and a pyridone ring. It is therefore not surprising that 1 has attracted the attention of the organic synthesis community. The first

Facile synthesis of functionalized spiro[indoline-3,2'-oxiran]-2-ones by Darzens reaction

• Qin Fu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 918–924, doi:10.3762/bjoc.9.105

• ; oxindole; oxirane; spiro-epoxyoxindole; spirooxindole; Introduction The spirooxindole unit is a privileged heterocyclic motif that forms the core structure of a large family of natural alkaloids and many pharmacological agents with important bioactivity and interesting structural properties [1][2][3][4][5

Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis

• Stephan Klopries,
• Uschi Sundermann and
• Frank Schulz

Beilstein J. Org. Chem. 2013, 9, 664–674, doi:10.3762/bjoc.9.75

• A-thioesters prior to their enzyme-catalyzed transfer onto the polyketide synthase. Control over the selection of malonic acid building blocks promises great potential for the experimental alteration of polyketide structure and bioactivity. One requirement for this endeavor is the supplementation of

Efficient synthesis of phenylene-ethynylene rods and their use as rigid spacers in divalent inhibitors

• Francesca Pertici,
• Norbert Varga,
• Arnoud van Duijn,
• Matias Rey-Carrizo,
• Anna Bernardi and
• Roland J. Pieters

Beilstein J. Org. Chem. 2013, 9, 215–222, doi:10.3762/bjoc.9.25

• 24 is a mimic for DC-SIGN inhibition and its bioactivity will be tested elsewhere. Inhibition studies The inhibitory potency of 22 for LecA was studied in an ELISA type assay by using a glycochip as the solid phase [10]. In this assay an IC50 value of 0.9 μM was determined (Table 1). This compared

Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

• Matthias G. J. Baud,
• Thomas Leiser,
• Vanessa Petrucci,
• Mekala Gunaratnam,
• Stephen Neidle,
• Franz-Josef Meyer-Almes and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2013, 9, 81–88, doi:10.3762/bjoc.9.11

• , Schnittspahnstraβe 12, 64287 Darmstadt, Germany Cancer Research UK Biomolecular Structure Group, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom 10.3762/bjoc.9.11 Abstract There has been significant interest in the bioactivity of the natural product psammaplin A, most recently as a

The multicomponent approach to N-methyl peptides: total synthesis of antibacterial (–)-viridic acid and analogues

• Ricardo A. W. Neves Filho,
• Sebastian Stark,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2012, 8, 2085–2090, doi:10.3762/bjoc.8.234

• cytotoxicity in a MTT assay on an undisclosed cell line [7]. Albeit that these two reports on the toxicity of extracts containing constituent 1 were very intriguing, no further biological screening of the pure substance has been performed to date. The connection between compound 1 and the bioactivity of the

• and N-methylated amino groups demanded harsher than usual conditions, upon which the desired viridic acid (1) was obtained in just 5% overall yield. The lack of sufficient amounts of isolated materials from natural sources did not allow for reliable bioactivity tests, and the demand for higher

Total synthesis and biological evaluation of fluorinated cryptophycins

• Christine Weiß,
• Tobias Bogner,
• Benedikt Sammet and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 2060–2066, doi:10.3762/bjoc.8.231

• are usually good substrates for the P-glycoprotein efflux pump resulting in a decreased bioactivity. Structures of cryptophycin-1 (1) and -52 (2). Fluorinated derivatives of cryptophycin-1 and -52 [20][21][22]. Access to the trifluoromethyl substituted unit A-building block 16. Reagents and conditions

An efficient access to the synthesis of novel 12-phenylbenzo[6,7]oxepino[3,4-b]quinolin-13(6H)-one derivatives

• Wentao Gao,
• Guihai Lin,
• Yang Li,
• Xiyue Tao,
• Rui Liu and
• Lianjie Sun

Beilstein J. Org. Chem. 2012, 8, 1849–1857, doi:10.3762/bjoc.8.213

• block for the synthesis of manifold biologically and pharmaceutically important compounds [25][26]. As a consequence, the remarkable bioactivity surrounding the benzoxepine moiety has elicited a significant amount of interest as demonstrated by synthetic work already published [27][28][29][30]. In light