Superoxide chemistry revisited: synthesis of tetrachloro-substituted methylenenortricyclenes

• Basavaraj M. Budanur and
• Faiz Ahmed Khan

Beilstein J. Org. Chem. 2014, 10, 2531–2538, doi:10.3762/bjoc.10.264

• of the superoxide ion leading to the synthesis of tetrachloroaryl/vinyl-substituted nortricyclenes through its dual mode of action has been reported. KO2 was found to be superior and the only reagent to perform this kind of reaction over other conventional bases. Addition of the antioxidant BHT (2,6

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

• analysis of proteins is the activity-based protein profiling (ABPP) [11][12]. This proteomic strategy uses small probes designed to target active members of enzyme families [13]. These are often based on natural products to investigate their protein targets and eventually their mode of action [14][15

• terminus without loss of function [35]. Thus the alkyne modified α,β,γ,δ-unsaturated aldehyde 10 can serve as a tool for the elucidation of the mode of action of the compound class of polyunsaturated aldehydes. DDY (10) was initially transformed with L-lysine to form an imine before CuAAC was performed

Photo, thermal and chemical degradation of riboflavin

• Muhammad Ali Sheraz,
• Sadia Hafeez Kazi,
• Sofia Ahmed,
• Zubair Anwar and
• Iqbal Ahmad

Beilstein J. Org. Chem. 2014, 10, 1999–2012, doi:10.3762/bjoc.10.208

• and the existence of a greater amount of these anions (100%) than the phosphate anions (38%) at pH 7.0 in 1.0 M solutions [21][30]. Thus, phosphate and sulfate anions show some differences in their mode of action which was evident from the rate of formation of CDRF and LC in their presence. This was

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

• . inhibens or other TDA-producing bacteria from the Roseobacter clade as promising candidates to be used as probiotics in aquacultures [12]. The mode of action of TDA is unknown, but it is difficult to select resistant and tolerant strains from long-term exposures to sub inhibitory concentrations of TDA

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• derivatives and acrylate esters 44) in the presence of Pt((R,R)-Me-DuPhos) complexes (Scheme 14). However, the products 45 suffered from low enantioselectivities [121]. The mode of action is based on the activation of the P-nucleophile. The proposed mechanism includes the P–H oxidative addition to platinum

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• the photoreactive derivative proved to be less active by a factor of at least 200. COMPARE analysis indicated tubulin interaction as likely mode of action of malevamide D. Keywords: cytotoxicity; diazirines; dolastatin analogs; marine natural products; peptides; total synthesis; Introduction The

• subnanomolar range (IC50 values about 0.7 nM). Closely related to malevamide D (1) is isodolastatin H (2), which is also active in vivo, but slightly weaker than dolastatin 10 (3) [2]. Although there has been no study regarding the mode of action, it can be assumed that malevamide D (1) acts similarly to

• ), and PXF-1118 (pleuramesothelioma, IC70 > 100 nM, IC50 about 50 nM, each). Diazirinyl-substituted malevamide D 30 was about 200 times less cytotoxic than 1. To obtain clues on the likely mode of action of 1 and 30, the in vitro activity data were compared with those of 177 reference compounds by

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• ], antimalaria and anticancer [10][11][22][23][24][25] as well as diverse further bioactivities. Recently it was discovered that prieurianin (2) impairs the actin cytoskeleton by a mechanism that does not involve direct interaction with actin suggesting that its mode of action differs from previously known

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• . Gaich et al. [38][39] used the DVCPR in a biosynthetic investigation targeting the dimethylallyltryptophan synthase. In order to test the biosynthetic hypothesis of the mode of action of the 4-prenylation of indoles by Arigoni and Wenkert (starting from L-tryptophan and dimethylallyl pyrophosphate

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

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

• carcinoma cell line Colo 320. Due to the lack of a larger portfolio of survivin antagonists, SF002-96-1 may serve as lead structure for the development of novel cancer therapeutics. Further investigations on the cellular targets and the mode of action of the compound are now under way. Experimental General

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

• farming industry and also has potent killing activity against insects, nematodes and fungi. The mode of action of antimycins is to inhibit cytochrome c reductase in the electron transport chain and halt respiration. However, more recently, antimycin A has attracted attention as a potent and selective

• inhibitor of the mitochondrial anti-apoptotic proteins Bcl-2 and Bcl-xL. Remarkably, this inhibition is independent of the main mode of action of antimycins such that an artificial derivative named 2-methoxyantimycin A inhibits Bcl-xL but does not inhibit respiration. The Bcl-2/Bcl-xL family of proteins are

• -formamidosalicylic acid moiety and they comprise more than 40 known members (Figure 1) [15][16][17][18][19][20][21][22]. Antimycins can undergo base-catalysed decomposition resulting in the production of volatile blastmycinones and butenolides [23]. The main mode of action of antimycins is to inhibit cytochrome c

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• groove of double-stranded DNA [4][5]. While the mode of action of anthracyclines is still not fully understood, it is widely accepted that these chemotherapeutic agents form a ternary complex with double-stranded DNA and topoisomerase II thereby leading to DNA damage and cell death [6][7]. They are used

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

• of staurosporine (26), is currently in clinical trials for the treatment of acute myeloid leukemia [20]. Although rebeccamycin (28) and its congeners only differ in the lack of the second glycosidic linkage, a completely different mode of action is effective. By stabilizing the topoisomerase I DNA

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• mode of action of OC-23. The chiral thioureas OC-28 to OC-44 for the desymmetrization of meso-aziridines. The chiral guanidines (OC-45 to OC-48). The proposed activation mode of OC-46. The chiral 1,2,3-triazolium chlorides OC-49 to OC-55. Early organocatalysts for enantioselective desymmetrization of

Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes

• Tony Taldone,
• Anna Rodina,
• Erica M. DaGama Gomes,
• Matthew Riolo,
• Hardik J. Patel,
• Raul Alonso-Sabadell,
• Danuta Zatorska,
• Maulik R. Patel,
• Sarah Kishinevsky and
• Gabriela Chiosis

Beilstein J. Org. Chem. 2013, 9, 544–556, doi:10.3762/bjoc.9.60

• testament to this, there are numerous ongoing clinical trials evaluating Hsp90 inhibitors from a variety of chemotypes [4]. Although there are potentially numerous ways to block the activity of Hsp90, the most successful to date, as exemplified by its exclusivity in mode of action by those advanced to

Zanthoxoaporphines A–C: Three new larvicidal dibenzo[de,g]quinolin-7-one alkaloids from Zanthoxylum paracanthum (Rutaceae)

• Fidelis N. Samita,
• Louis P. Sandjo,
• Isaiah O. Ndiege,
• Ahmed Hassanali and
• Wilber Lwande

Beilstein J. Org. Chem. 2013, 9, 447–452, doi:10.3762/bjoc.9.47

• from the same family, and the mode of action of these alkaloids could be the same. Zanthoxoaporphine A (2) and liriodenine, which are oxoaporphines, are more active than dicentrine (aporphine). The isoquinoline moiety could be the pharmacophore of this class of compounds and the presence of a ketone at

Asymmetric Diels–Alder reaction with >C=P– functionality of the 2-phosphaindolizine-η¹-P-aluminium(O-menthoxy) dichloride complex: experimental and theoretical results

• Rajendra K. Jangid,
• Nidhi Sogani,
• Neelima Gupta,
• Raj K. Bansal,
• Moritz von Hopffgarten and
• Gernot Frenking

Beilstein J. Org. Chem. 2013, 9, 392–400, doi:10.3762/bjoc.9.40

• , namely C1 (δ = 132.7 ppm, 1JPC = 36.0 Hz), C3 (δ = 54.5 ppm, 1JPC = 31.7 Hz) and C9 (δ = 33.6 ppm, 1JPC = 44.5 Hz) are identified readily by large values of 1JPC [33][34]. The 13C NMR signals due to the O-menthoxy moiety were assigned on the basis of the reported results [35]. Mode of action of the

• theoretically the mode of action of the chiral auxiliary in directing the complete diastereoselectivity of the DA reactions. The following model DA reactions (Scheme 5) were calculated at the DFT (B3LYP/6-31+G*) level. Computational calculations It has been reported that for determining activation free energies

Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups

• H. Bauke Albada,
• Alina-Iulia Chiriac,
• Michaela Wenzel,
• Maya Penkova,
• Julia E. Bandow,
• Hans-Georg Sahl and
• Nils Metzler-Nolte

Beilstein J. Org. Chem. 2012, 8, 1753–1764, doi:10.3762/bjoc.8.200

• of ~90 µM, indicating a potentially interesting therapeutic window. Both the killing kinetics and growth inhibition studies presented in this work point to a membrane-based mode of action for these two peptides, each having different kinetic parameters. Keywords: antimicrobial peptides; arginine

• details on the mode of action. Specifically, proteomic analysis of the changes in the bacterial proteome as result of exposure to these synAMPs, and prokaryotic and eukaryotic membrane model systems will be used to precisely determine if it is simply a membrane-based mechanism or if there are more factors

• . While we attempt to elucidate the mode of action of these synAMPs, we are also interested in a detailed understanding of the effects of the organometallic fragment on the activity – for example by determining the contributions of hydrogen-bond forming processes in membrane environments – and the effect

Binaphthyl-anchored antibacterial tripeptide derivatives with hydrophobic C-terminal amino acid variations

• John B. Bremner,
• Paul A. Keller,
• Stephen G. Pyne,
• Mark J. Robertson,
• K. Sakthivel,
• Kittiya Somphol,
• Dean Baylis,
• Jonathan A. Coates,
• John Deadman,
• Dharshini Jeevarajah and
• David I. Rhodes

Beilstein J. Org. Chem. 2012, 8, 1265–1270, doi:10.3762/bjoc.8.142

• included in Table 2. This tripeptide derivative 9 showed similar, if slightly weaker, antibacterial activity against these strains, apart from VSE, against which it was significantly less potent than 2c. Although the mode of action of the tripeptide derivatives has not been established, our earlier results

• on compounds of type 1 (Figure 1) and related cyclic systems implicated the possibility of more than one mode of action [8]. As noted for other cationic peptide derivatives [9][10][11][12], cell membrane damage could well be one of these actions, together with some more specific interactions. Dual

Design of a novel tryptophan-rich membrane-active antimicrobial peptide from the membrane-proximal region of the HIV glycoprotein, gp41

• Evan F. Haney,
• Leonard T. Nguyen,
• David J. Schibli and
• Hans J. Vogel

Beilstein J. Org. Chem. 2012, 8, 1172–1184, doi:10.3762/bjoc.8.130

• are unstructured in solution, and they adopt amphipathic α-helices when bound to a phospholipid bilayer [3][23]. This binding to the bacterial membrane is often related to a membrane-destabilizing mode of action, which ultimately leads to bacterial cell death [24]. However, recent evidence suggests

• that membrane binding may be a part of a more complex mode of action involving multiple targets of inhibition [21][25]. In addition to their membrane-binding properties, many AMPs are typified by a high proportion of Trp and cationic amino acids [5][6]. The Trp residues are unique because of their

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• ) structures of naturally occurring alkaloids bearing aminoacetal moieties and a proposed mode of action of quinocarcin. Four-step synthesis of hexacyclic skeleton 25. Four-step synthesis of hexacyclic skeleton 30. Parallel and four-step synthesis of tetracyclic skeletons 39–42 and 47–48. Synthesis of branched

Synthesis of szentiamide, a depsipeptide from entomopathogenic Xenorhabdus szentirmaii with activity against Plasmodium falciparum

• Friederike I. Nollmann,
• Andrea Dowling,
• Marcel Kaiser,
• Klaus Deckmann,
• Sabine Grösch,
• Richard ffrench-Constant and
• Helge B. Bode

Beilstein J. Org. Chem. 2012, 8, 528–533, doi:10.3762/bjoc.8.60

• bioactive natural products and the importance of a broad bioactivity testing of isolated compounds in order to find a biological activity and thus a biological function of such natural products. Work in the Bode lab currently concentrates on the identification of the mode of action of 1 in insects and

Planar-bilayer activities of linear oligoester bolaamphiphiles

• Jonathan K. W. Chui,
• Thomas M. Fyles and
• Horace Luong

Beilstein J. Org. Chem. 2011, 7, 1562–1569, doi:10.3762/bjoc.7.184

• underlying mechanism? One line of possibilities relates to the underlying “system property” mentioned earlier. It is known that pure lipids near their phase transitions can show single-channel conductance activities; while the specific mode of action depends on the identity of the lipid, discrete conductance

Highly efficient cyclosarin degradation mediated by a β-cyclodextrin derivative containing an oxime-derived substituent

• Michael Zengerle,
• Florian Brandhuber,
• Christian Schneider,
• Franz Worek,
• Georg Reiter and
• Stefan Kubik

Beilstein J. Org. Chem. 2011, 7, 1543–1554, doi:10.3762/bjoc.7.182

• degradation and, in particular, the observed enantioselectivity are good indications that noncovalent interactions between the cyclodextrin ring and the substrate, presumably involving the inclusion of the cyclohexyl moiety of cyclosarin into the cyclodextrin cavity, contribute to the mode of action. Among

• , acetylcholinesterase (AChE). Moreover, the results indicate that the mode of action of these cyclodextrin derivatives involves the formation of an inclusion complex with the OP. The question thus arises as to whether suitable cyclodextrin derivatives could also be used in vivo as antidotes against OP poisonings. Such

• treatment of OP poisonings. Their mode of action involves reactivation of the OP-inhibited acetylcholinesterase [29], yet previous work has also indicated that certain oximes are able to cleave OPs directly [30]. We show that some of our cyclodextrin derivatives efficiently reduce GF concentrations in