Selective bromochlorination of a homoallylic alcohol for the total synthesis of (−)-anverene

• Frederick J. Seidl and
• Noah Z. Burns

Beilstein J. Org. Chem. 2016, 12, 1361–1365, doi:10.3762/bjoc.12.129

• regio- and enantioselectivity. Disclosed herein, this discovery has enabled the first total synthesis of (−)-anverene (1) (Scheme 1, bottom), a secondary metabolite from the algae Plocamium cartilagineum with selective antibiotic activity against vancomycin-resistant Enterococcus faecium (VREF) [10

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• only been described bioinformatically [123]. Subtilosin is a Bacillus RiPP antibiotic that belongs to the sactipeptide family of natural products that are defined by the presence of one or more sulphur to α-carbon bonds [125]. Three thioethers in subtilosin are formed by a single SPASM protein, AlbA

• understood, such as enterocin AS-48 [137][138] (also known as bacteriocin 21 [139]). AS-48 is a 70-residue cyclic antibiotic produced by Enterococcus faecalis and was recently shown to enhance the ability of the strain to colonise the mammalian gastrointestinal tract by outcompeting bacteria that are

Antibacterial structure–activity relationship studies of several tricyclic sulfur-containing flavonoids

• Lucian G. Bahrin,
• Henning Hopf,
• Peter G. Jones,
• Laura G. Sarbu,
• Cornelia Babii,
• Alina C. Mihai,
• Marius Stefan and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2016, 12, 1065–1071, doi:10.3762/bjoc.12.100

• of one of the greatest problems faced by modern medicine: multidrug-resistant bacteria. Resistance may arise via various mechanisms including changes in cell-wall permeability, target site mutation, antibiotic inactivation and the development of efflux pumps that transport the drugs out of the cell

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• metabolites and for the biosynthesis of antimicrobials [59]. In these studies, PKS genes could be amplified, sequenced and compared with known sequences in the BLAST database. The potential of producing active molecules was established by using disc diffusion antibiotic activity testing of the bacterial

• cultivation in NaBr-containing medium was selected for antibiotic production. The diminished strength of salinity in the medium implies an optimal salt range concentration for growth of 0.5–1% (w/v), at pH 7.2 and a temperature of 27 °C. Fermentation and the production of antibiotic compounds were performed

A cross-metathesis approach to novel pantothenamide derivatives

• Jinming Guan,
• Matthew Hachey,
• Lekha Puri,
• Vanessa Howieson,
• Kevin J. Saliba and
• Karine Auclair

Beilstein J. Org. Chem. 2016, 12, 963–968, doi:10.3762/bjoc.12.95

• larger groups via cross-metathesis. The method was applied in the synthesis of a new pantothenamide with improved stability in human blood. Keywords: antibiotic; antiplasmodial; coenzyme A; metathesis; pantothenate; Introduction Bacteria, fungi, and parasites are all rapidly acquiring resistance to

• currently applied antimicrobials and as a result, our ability to treat infections effectively is diminishing. Efforts to control infections in this resistance era have taken a variety of paths from a renewed push for novel antimicrobial agents to a fresh understanding of antibiotic resistance mechanisms [1

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• which have a uridine-derived core structure in common. Their antibiotic potency is based on the inhibition of MraY, thereby blocking a membrane-associated intracellular step of bacterial cell-wall biosynthesis. The structure elucidation was carried out using one- and two-dimensional NMR experiments as

• group B. Capuramycin, a nucleoside antibiotic isolated in 1986 from Streptomyces griseus, shares the uracil-derived nucleoside moiety with the muraymycins [33][34]. The antibiotic FR-900493, which is structurally closely related to muraymycins, was isolated from Bacillus cereus and characterised in 1990

• activity against Gram-positive bacteria, Pseudomonas and M. tuberculosis [48]. The related liposidomycins display good activity against M. phlei, while they are not active against a range of other bacteria [45]. Mode of action To develop an effective antibiotic one needs to choose a target that is

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• used to treat HIV/AIDS [5]. Gatifloxacin is an important fluoroquinolone antibiotic [6]. Despite the high frequency appearance of piperazines in small-molecule pharmaceuticals, over 80% only contain substituents at the two nitrogen atoms and a very small fraction of them have simple carbon

Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

• Guozheng Huang,
• Simon Schramm,
• Jörg Heilmann,
• David Biedermann,
• Vladimír Křen and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 662–669, doi:10.3762/bjoc.12.66

• (kernels) of H. wightiana, contains besides hydnocarpin mainly cyclopentenoic fatty acids [16], which show pronounced antibiotic activity and inhibit multiplication of mycobacteria [17]. Combination of these antibiotics together with hydnocarpin (MDR inhibitor) helped to treat such a persistent disease

• -methoxyhydnocarpin has been described to enhance the antimicrobial activity of berberine [19]. In the light of steadily growing antibiotic resistance any potent and nontoxic MDR inhibitor is of utmost importance. Hydnocarpin has also antineoplastic activity due to sensitizing multidrug-resistant cancer cell lines

Correction: Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 608–610, doi:10.3762/bjoc.12.59

• ; computational chemistry; drug design; molecular recognition; relaxed force constants; Our original publication contains an erratic number of predicted antibiotic structures in Scheme 2. With this Erratum we provide the corrected Scheme 2. Scheme 2 in the original article: Predicted new linezolid-like

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• further characterized by their large genome sizes and their striking potential for the production of structurally diverse natural products with antimicrobial activities [12][30][31][32][33][34][35]. For many years, it has been speculated whether antibiotic biosynthesis is functionally linked to the

• with a minimal inhibitory concentration (MIC) of 1 µg/mL [75]. Its mode of action was deduced after genetic characterization of myxovirescin-resistant E. coli mutants [81]. The antibiotic interferes with cell-wall biosynthesis by inhibiting a novel target, i.e., the type II signal peptidase LspA, which

• is involved in the maturation of lipoproteins required for murein biosynthesis [81]. Myxovirescin A1 (also known as antibiotic TA) and its derivatives seem to be of particular importance for the predatory lifestyle of M. xanthus DK1622. Gene deletion experiments demonstrated that a loss of

Studies on the synthesis of peptides containing dehydrovaline and dehydroisoleucine based on copper-mediated enamide formation

• Franziska Gille and
• Andreas Kirschning

Beilstein J. Org. Chem. 2016, 12, 564–570, doi:10.3762/bjoc.12.55

• moieties present in the antibiotic myxovalargin is reported. Peptide formation is based on a copper-mediated C–N cross-coupling protocol between an acyl amide and a peptidic vinyl iodide. The presence of a neighboring arginine in the vinyl iodide posed a challenge with respect to the choice of the

• the olefinic double bond (Scheme 6). We based the stereochemical assignment on NMR spectroscopy which included nOe experiments. Conclusion In conclusion, we report on the synthesis of dehydrovaline and dehydroisoleucine-containing oligopeptides as found in the peptide antibiotic myxovalargin using a C

Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• : compliance constants; computational chemistry; drug design; molecular recognition; relaxed force constants; Introduction Antibiotic resistance is one of the major health problems in modern societies, causing millions of deaths per year [1][2][3]. Although Alexander Fleming recognized the importance of the

• -resistant pneumococci, for example, led to the description of the situation today as an “Antibiotic Armageddon” [5]. In a recent WHO report it is concluded that “the problem is so serious that it threatens the achievements of modern medicine. A post-antibiotic era, in which common infections and minor

• therefore plays a central role for the understanding of the relevant recognition processes [8][9]. Examples of antibiotic drug classes that bind the ribosomal 50S subunit are chloramphenicol, puromycin, anisomycin, streptogramina A, and macrolides [10][11]. Those compounds interact with different sites

Mycothiol synthesis by an anomerization reaction through endocyclic cleavage

• Shino Manabe and
• Yukishige Ito

Beilstein J. Org. Chem. 2016, 12, 328–333, doi:10.3762/bjoc.12.35

• -containing lincosamide antibiotic [19]. Due to the limited availability of MSH from M. smegmatis cell culture (<1.5 mg of MSH from 1 L culture) [20], the chemical synthesis of MSH is highly desired. Bewley et al. and Lee and Rosazza independently reported the synthesis of MSH and determined the absolute

Natural products from microbes associated with insects

• Christine Beemelmanns,
• Huijuan Guo,
• Maja Rischer and
• Michael Poulsen

Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34

• synthetic compound libraries to counteract a declining number of new antibiotic entities in the drug development pipeline has largely failed [3], and the current poor repertoire represents a ”ticking time bomb”. Societies face, as a consequence of the rapid globalization and intensive use of antibiotics, an

• increasing threat of multidrug-resistant pathogens, which are responsible for the growing numbers of lethal infections [4][5]. The urge to discover novel lead-like antibiotic compounds and to refill the industrial antibiotic pipeline to meet current and future societal challenges has never been greater [6

• find more or less useful bioactivities. More rational approaches are necessary to enhance the efficacy, efficiency, and speed of drug discovery in general and antibiotic discovery in particular. In recent years, the exploration of the chemical basis of specific and well-described bacteria–host or

A convergent, umpoled synthesis of 2-(1-amidoalkyl)pyridines

• Tarn C. Johnson and
• Stephen P. Marsden

Beilstein J. Org. Chem. 2016, 12, 1–4, doi:10.3762/bjoc.12.1

• as the antitumour antibiotic kedarcidin chromophore 1 [2] and the RNA polymerase inhibitor cyclothiazomycin B1 2 [3] (Figure 1). Additionally, the motif is commonly incorporated into synthetic pharmaceutical candidates, for example in the factor XIa inhibitor 3 [4], the orally-active renin inhibitor

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

• Hang Ren,
• Haoyun An,
• Paul J. Hatala,
• William C. Stevens Jr,
• Jingchao Tao and
• Baicheng He

Beilstein J. Org. Chem. 2015, 11, 2509–2520, doi:10.3762/bjoc.11.272

• -D-riboside (6-β-D-MPR) is an isolated antibiotic agent that possesses potent antifungal, antiviral, and antitumor activities [44]. In order to explore the effect of fluorine on the biological activity of this pharmacophore, we synthesized 6-methylpurine-3’-deoxy-3’-fluoro-β-D-riboside (4) (Scheme 2

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• deduced from these labeling experiments as (2’R) via comparison of the retention times of both compounds to naturally occurring 8 on a homochiral stationary LC phase. To investigate the proposed structure of 7, which likely exhibits the antibiotic properties connected to the bacterial strain as a highly

• function and subsequent ring closure would then lead to the proposed antibiotic 7. The other oxygen atom is lost during biosynthesis und is therefore undetectable. This example shows how well-designed labeling experiments can support biosynthetic investigations especially on highly derivatized and altered

• gutingimycin, a guanine-adduct of 9 [27]. However, very little was known about the biosynthetic assembly of the complex antibiotic. Feeding of [1-13C]-, [2-13C]- and [1,2-13C2]acetate to S. bottropensis and analysis of the produced 9 via 13C NMR yielded the carbon origins of the polyketide core. The regular

Bromotyrosine-derived alkaloids from the Caribbean sponge Aplysina lacunosa

• Qun Göthel,
• Thanchanok Sirirak and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2334–2342, doi:10.3762/bjoc.11.254

• activities, including antiviral [2], antibiotic [3][4][5], Na+/K+ ATPase inhibition [6][7][8], anti-HIV [9][10], antifungal [11], histidine-H3 antagonist [12], cytotoxic [13][14], and antimalarial activities [15][16][17]. During our investigation of the chemical constituents of Aplysina lacunosa (Aplysinidae

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

• Madhuri Vangala and
• Ganesh P. Shinde

Beilstein J. Org. Chem. 2015, 11, 2289–2296, doi:10.3762/bjoc.11.249

• compounds with a wide range of applications spanning different chemistry disciplines. 2-Oxazoline derivatives are extensively studied due to their presence in numerous bioactive natural products [1][2][3] and synthetic drugs with anticancer, antibiotic, antidiabetic, and antifungal properties (Figure 1, 1–4

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• example, in cases of calyculin and okadaic acid it has been proposed [18][19] that the spiroketal unit acts as a β-turn mimic. Naturally occurring spiroketals exhibit a wide spectrum of biological activity: anticancer [20][21][22], antibiotic [23][24], antifungal [25], anthelmintic [26] and anti-HIV [27

• antibiotic. This 14-membered macrolide contains a [4.4]spiroketal unit connecting 6-C–O–9-C–O–12-C. Stereochemistry at position 9-C of this spiroketal was determined by combination of NMR spectroscopy and molecular modelling [42]. The kinetics of its formation has also been extensively studied [43][44][45

• ][46]. Most recently, in the latest revision of the reaction pathway Hassanzadeh et al. showed that this macrolide spiroketal in acid media exists in equilibrium with the 9,12-hemiacetal of erythromycin A [47]. The closely related antibiotic clarithromycin (structurally related to our starting aglycon

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• hydroxamic acid (5, SAHA, Figure 1) [43]. Another early application of microreactor technology was reported in 2005 detailing the assembly and subsequent decoration of the fluoroquinolinone scaffold 6 resulting in the synthesis of a library of analogues including the well-known antibiotic ciprofloxacin (6

DBU-promoted carboxylative cyclization of o-hydroxy- and o-acetamidoacetophenone

• Wen-Zhen Zhang,
• Si Liu and
• Xiao-Bing Lu

Beilstein J. Org. Chem. 2015, 11, 906–912, doi:10.3762/bjoc.11.102

• pharmacologically potent compounds (Figure 1) [4][5]. Warfarin, for example, is an anticoagulant widely used to prevent thrombosis [2]; Novobiocin has long been established as an aminocoumarin antibiotic [3]. Recent studies revealed that the anticoagulant Dicumarol is able to inhibit the growth of pancreatic cancer

A simple and efficient method for the preparation of 5-hydroxy-3-acyltetramic acids

• Johanna Trenner and
• Evgeny V. Prusov

Beilstein J. Org. Chem. 2015, 11, 323–327, doi:10.3762/bjoc.11.37

• antibiotic properties, we were interested to investigate their activities in various assays but the literature survey showed that synthetic approaches to 5-hydroxylated 3-acyltetramic acids are essentially non-existent, although M. Coster reported the synthesis of 5-hydroxytetramic acid ethers by

Copper-catalyzed cascade reactions of α,β-unsaturated esters with keto esters

• Zhengning Li,
• Chongnian Wang and
• Zengchang Li

Beilstein J. Org. Chem. 2015, 11, 213–218, doi:10.3762/bjoc.11.23

• and its analogues, sharing the similar structure of a γ-lactone with an attached β-carboxylic acid, are widely found in natural products. Related syntheses have been actively explored due to the potential antitumor and antibiotic activities of these compounds [1][2][3][4]. The synthesis methods were

Synthesis of antibacterial 1,3-diyne-linked peptoids from an Ugi-4CR/Glaser coupling approach

• Martin C. N. Brauer,
• Ricardo A. W. Neves Filho,
• Bernhard Westermann,
• Ramona Heinke and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2015, 11, 25–30, doi:10.3762/bjoc.11.4

• orders of magnitude of concentration anyhow. Therefore no further attempt to optimize for an equal product distribution was deemed necessary. To gain insight into the antibiotic potential of the products, single compound dimers 8a–j were subjected to a preliminary evaluation against Bacillus subtilis