Consecutive hydrazino-Ugi-azide reactions: synthesis of acylhydrazines bearing 1,5-disubstituted tetrazoles

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2017, 13, 2596–2602, doi:10.3762/bjoc.13.256

• linatine [24] and the antibiotic negamycin, active against Gram-negative bacteria [25], among others [26]. Furthermore, trisubstituted acylhydrazines were found to serve as tertiary amide bioisosters [27]. Therefore, it is highly desirable to have a method that allows an easy incorporation of hydrazino

Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

• Xinli Pan,
• Nicole Domin,
• Sebastian Schieferdecker,
• Hirokazu Kage,
• Martin Roth and
• Markus Nett

Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242

• an agar diffusion assay against a standard selection of Gram-positive and Gram-negative bacteria as well as some fungi. However, the compound was inactive at all tested concentrations. A literature search revealed that 1 is the first microbial terpene possessing an octahydro-1H-indene backbone

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• be less active than nitroxoline (being the reference substance). The antimicrobial effect of the heterocycles studied is different depending on each bacterical strain; however, some rules can be seen. Only a few substances inhibited the growth of Gram-negative bacteria (strains of E. coli and P

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• isoprenyl side chain is an influential factor of the group- (or species-) specific pheromonal activity [25]. Intriguingly, the same applies for group- (or species-) specificity in Gram negative bacteria because the chemical structure and length of the acyl side chain in acylhomoserine lactones, which are

• quorum sensing pheromones secreted by Gram negative bacteria, have a great effect on the group specificity (Figure 3B) [33][34]. Modifications of the lipophilic side chain in quorum sensing pheromones are probably a common strategy to acquire group specificity in bacteria. ComQ Molecular genetic analyses

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• -positive bacteria, including resistant strains [2][9][20] and Mycobacterium species [21]. No activity was observed against Gram-negative bacteria (except for Neisseria gonorrhoeae), fungi or yeast [9]. The antibacterial activity arises through inhibition of cell wall synthesis [22] by prevention of

• revised from S to R, upon total synthesis [33]. The mannopeptimycins contain a unique sugar substituted hydroxyenduracididine residue (blue, Figure 5). The mannopeptimycins displayed moderate activity against Gram-positive bacteria, including MRSA, but only exhibited weak activity against Gram-negative

• bacteria [7] with the primary cellular target deduced to be bacterial cell wall synthesis [34]. Extensive derivatisation of both mannopeptimycin α (12) and β (13) was undertaken to improve the antibacterial activity of the parent natural products (highlighted in blue, Figure 6). An array of ether [35][36

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

• fluorine atom in their molecular structure. This suggests that the activity against Gram negative bacteria is less dependent on the nature of the introduced heavier halogen (Cl, Br or I). Compound 1 was found to be slightly more potent against S. aureus in terms of bacteriostatic properties than the other

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

• , Enterococcus MIC: 16–64 µg/mL) but also a few Gram-negative bacteria (E. coli MIC: down to 0.03 μg/mL). Since the activity against wild-type E. coli is clearly lower (MIC > 128 μg/mL) [22], it is assumed that this might be an effect resulting from low membrane permeability. There are other naturally occurring

• either methionine for mureidomycins, napsamycins and sansanmycins or alanine in case of pacidamycins. Remarkably, these natural products share a urea peptide motif with the muraymycins. They are mainly active against Gram-negative bacteria, which is a noteworthy difference to the muraymycins and other

• with MIC values of 2 to 16 μg/mL, Enterococci with 16 μg/mL and higher to some Gram-negative bacteria (8 μg/mL). Against an E. coli mutant with increased membrane permeability, an MIC value below 0.03 μg/mL was obtained, suggesting that inhibition is a matter of cellular uptake of the compound. In vivo

Elucidation of a masked repeating structure of the O-specific polysaccharide of the halotolerant soil bacteria Azospirillum halopraeferens Au4

• Elena N. Sigida,
• Yuliya P. Fedonenko,
• Alexander S. Shashkov,
• Nikolay P. Arbatsky,
• Evelina L. Zdorovenko,
• Svetlana A. Konnova,
• Vladimir V. Ignatov and
• Yuriy A. Knirel

Beilstein J. Org. Chem. 2016, 12, 636–642, doi:10.3762/bjoc.12.62

• , often non-stoichiometric, are not uncommon for Gram-negative bacteria. They occur independently of the polymerization mechanism [21][22] and often are associated with temperate bacteriophages that bear the corresponding transferases. Such alterations in certain O-antigen structures of emerging human

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

• through specialized structures [23]. Other predatory bacteria are known to directly penetrate the prey cell in a process called diacytosis [24][25] or to selectively invade the periplasm of Gram-negative bacteria [26]. The corresponding behaviors are referred to as endobiotic and periplasmic predation

• effects on Gram-negative strains are in general much weaker. Gram-negative bacteria of the genus Wolbachia, which have emerged as a new target for filariasis control, constitute a significant exception [103]. Already in the 1980s, incorporation studies with labeled precursors revealed the inhibition of

• Cystobacter fuscus [108]. The pentapeptide is broadly active against Gram-positive as well as Gram-negative bacteria and was shown to selectively inhibit bacterial protein synthesis. Its specific site of inhibition is the 50S subunit of the ribosome, where althiomycin interferes with the peptidyl transferase

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• leukemia MH-60 cells [42]. Testing the inhibitory effect of corallopyronin A (34) against various microorganisms revealed promising activity against Gram-positive bacteria, but no relevant effect on Gram-negative bacteria (only at concentrations >100 µg/mL activity was observed). Against Staphylococcus

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

• analyses and computational calculations [11][12]. Recently, N-acyl variants of MSH homologs, such as formyl, propanoyl, and succinoyl, have been reported [13][14][15]. Gram-negative bacteria and most Eukaryotes utilize glutathione as a low-molecular-weight thiol for maintaining a reducing environment in

• Gram-negative bacteria. MSH undergoes metal-catalyzed autoxidation more rapidly than glutathione [16]. The biosynthetic pathway of MSH has been well investigated; MSH is synthesized from 1-inositol phosphate and uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) in five steps [15]. It is used by

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

• comparison with 21, compound 3 showed one extra aliphatic carbon and was named aplysinin B. The new compounds 14-debromo-11-deoxyfistularin-3 (1) and aplysinin A (2) were tested for their antimicrobial activity against different Gram-positive and Gram-negative bacteria, fungi, and for their antiproliferative

SmI₂-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen B

• Nils Marsch,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2015, 11, 1700–1706, doi:10.3762/bjoc.11.184

• natural product via X-ray analysis. Indiacen B (2) was tested against the Gram-positive bacteria Nocardioides simplex (1.7 µg/mL), Mycobacterium diernhoferi (no inhibition), and Mycobacterium sp. (8.3 µg/mL), and against the Gram-negative bacteria Escherichia coli TOL C (8.3 µg/mL), Chromobacterium

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• of Trichophyton mentagrophytes (MIC 6.2 µg/mL) and Epidermophyton floccosum (MIC 1.6 µg/mL) [87]. Though no activity was observed against the gram negative bacteria Escherichia coli and Pseudomonas aeruginosa, meridine (56) significantly inhibited the growth of the gram positive bacteria Bacillus

N-Alkyl derivatives of diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside; synthesis and antimicrobial activity

• Agata Walczewska,
• Daria Grzywacz,
• Dorota Bednarczyk,
• Małgorzata Dawgul,
• Andrzej Nowacki,
• Wojciech Kamysz,
• Beata Liberek and
• Henryk Myszka

Beilstein J. Org. Chem. 2015, 11, 869–874, doi:10.3762/bjoc.11.97

• glucopyranoside is presented. Evaluation of antibacterial and antifungal activities of these derivatives indicates that they have no inhibitory activity against Gram-negative bacteria, whereas many of the tested N-alkyl saponins were found to inhibit the growth of Gram-positive bacteria and human pathogenic fungi

• vitro activity against 5 strains of Gram-negative bacteria, 5 strains of Gram-positive bacteria, and 3 strains of human pathogenic fungi. Respective minimum inhibitory concentration (MIC) values determined by a serial dilution microplate method according to the guidelines of the Clinical and Laboratory

• inhibitory activity against the Gram-negative bacteria, such as Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris and Pseudomonas aeruginosa. In contrast, almost all the tested N-alkyl saponins were found to inhibit the growth of the Gram-positive bacteria (Table 2). Among the

Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators

• Michail Syrpas,
• Ewout Ruysbergh,
• Christian V. Stevens,
• Norbert De Kimpe and
• Sven Mangelinckx

Beilstein J. Org. Chem. 2014, 10, 2539–2549, doi:10.3762/bjoc.10.265

• reports supporting this theory, it has to be noted that this view point has been challenged and is still under debate among scientists [6][7]. Most Gram-negative bacteria use N-acylated homoserine lactones (AHLs) as signal molecules [8]. The general structure of these compounds consist of a lactone ring

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• carbapenems, which are powerful antibiotics with a broad spectrum of activity against Gram-positive and Gram-negative bacteria and are often used as antibiotics for many hard-to-treat bacterial infections, such as Escherichia coli and Klebsiella pneumoniae [88][89]. Resistance of bacterial strains to

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

• activity against the Gram-positive bacteria Staphylococcus aureus ATCC 25923 (IC50 1.8 μM), Staphylococcus epidermidis ATCC 12228 (IC50 0.9 μM) and Bacillus subtilis ATCC 6633 (IC50 1.8 μM), but was inactive (IC50 > 30 μM) against the Gram-negative bacteria Pseudomonas aeruginosa ATCC 10145 and Escherichia

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

• -positive and Gram-negative bacteria, fungi, and for antiproliferative activity. The results given in Table 4 show that siphonodictyal E3 (3) and cyclosiphonodictyol A (5) exhibited mild activity against the Gram-positive bacteria Staphylococcus aureus and Micrococcus luteus, while siphonodictyal E4 (4

• ) show cytotoxic activity against the L929 mouse fibroblasts, KB-31 epidermoid carcinoma, and the breast cancer cell line MCF7, although none of them showed activity in the antimicrobial assays against Gram-negative bacteria and the fungus Candida albicans. Many of the isolated compounds from Aka

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

• ). Nalidixic acid is a prototype quinolone antibiotic that has been used extensively as an effective treatment against both gram positive and gram negative bacteria. In general, quinolone antibiotics act by interfering with the enzymes DNA-gyrase and/or topoisomerase of bacteria [55]. Moxifloxacin (1.102

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

• susceptible Enterococcus faecalis (VSE, E1), vancomycin resistant E. faecium (VanA VRE, E2)), and 2 strains of Streptococcus pneumoniae, including multi-drug resistant strain (MDRSP, P9), as well as 3 species of Gram-negative bacteria, consisting of Pseudomonas aeruginosa and 2 strains of Haemophilus

• Gram-negative bacteria, no activity against E. coli and P. aeruginosa was found (MIC > 64 µg/mL, data not shown), consistent with the inactivity of 3-acyl and 3-carboxamide tetramic acids against these strains seen earlier [7][8][10]. This result is most likely explained by their poor cell permeability

Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues

• Xu-Wen Li,
• Jennifer Herrmann,
• Yi Zang,
• Philippe Grellier,
• Soizic Prado,
• Rolf Müller and
• Bastien Nay

Beilstein J. Org. Chem. 2013, 9, 1551–1558, doi:10.3762/bjoc.9.176

• previous reports [1], antibacterial activities (Table 4) were mainly observed on Gram-positive bacteria while Gram-negative bacteria were not affected, except Escherichia coli TolC which is deficient in the corresponding multidrug efflux transporter. The tested compounds were neither active on yeast

Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• bacterial cell-wall components including lipopolysaccharides and/or peptidoglycan (NOD1 or 2) along with those of bacterial flagellin [22][23][24][25]. Importantly, the NOD1 protein primarily recognizes Gram-negative bacteria, in contrast to the more widely studied sensor NOD2, which participates in

Chemoenzymatic synthesis and biological evaluation of enantiomerically enriched 1-(β-hydroxypropyl)imidazolium- and triazolium-based ionic liquids

• Paweł Borowiecki,
• Małgorzata Milner-Krawczyk and
• Jan Plenkiewicz

Beilstein J. Org. Chem. 2013, 9, 516–525, doi:10.3762/bjoc.9.56

• liquids Antibacterial and antifungal activities of the synthesized racemic CILs were evaluated against a wide range of microorganisms. The studies were conducted on three strains of gram-negative bacteria, two strains of gram-positive bacteria, and eight strains of fungi. For the preliminary screening of

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

• readily available to provide first SAR insight. The biological activities of the natural product and its derivatives against the Gram-negative bacterium Aliivibrio fischeri were evaluated. Keywords: antibiotic; anticancer; Gram negative bacteria; natural product; peptide coupling; peptides; peptoid