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

• activity. For example, what has now become the benchmark pantothenamide, N-pentylpantothenamide (1, Figure 1), is active against Escherichia coli [6] and Staphylococcus aureus [13], at minimum inhibitory concentrations (MICs) in the low micromolar range. Pantothenamides are however rapidly degraded by

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

• methicillin-resistant Staphylococcus aureus (MRSA) [18][19] and vancomycin-resistant Enterococcus (VRE) [20]. This development raises the demand for antibiotics exploiting yet unused modes of action. Potential targets within bacteria include peptidoglycan biosynthesis, protein biosynthesis, DNA and RNA

• efficacy was demonstrated for muraymycin A1 with an ED50 of 1.1 mg/kg in Staphylococcus aureus-infected mice. Five of the 19 naturally occurring compounds (i.e., muraymycins A1, A5, B6, C2 and C3) were capable of inhibiting both MraY and peptidoglycan synthesis at the lowest concentration tested (IC50

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

• being efficient inhibitors of the multidrug resistance (MDR) efflux pump (e.g., of Staphylococcus aureus): this activity had been serendipiously employed in traditional medicine (without knowledge of the mechanism) in the treatment of leprosy with chaulmoogra oil. This oil, which is obtained from fruits

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

• assembly lines were recently shown to account for the diverging frameworks of the western chain [100][101][102]. Myxopyronins and corallopyronins turned out to be highly active against Gram-positive bacteria with MIC values between 0.1 and 1.0 µg/mL for Staphylococcus aureus, whereas their inhibitory

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

• aureus a MIC of 0.097 µg/mL and against Bacillus megaterium of 0.39 µg/mL was obtained [40]. Myxopyronin B (37), the most active derivative of the myxopyronins, showed comparable activities, e.g., MIC of 0.3 and 0.8 µg/mL against S. aureus and B. megaterium, respectively [43]. In addition corallopyronin

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

• portion displayed in blue [15]. While only the S-enantiomer seems to be potent, linezolid shows activity against a wide range of Gram-positive bacteria such as vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae

• potency both in vitro and in vivo antibacterial activities [46]. Candidate 7 represents the active form of the prodrug torezolid, the phosphate disodium salt, which was synthetized in order to improve the solubility of its parent drug. Highly active against MRSA, MSSA (methicillin-sensitive Staphylococcus

• aureus), VRE and Hi (Haemophilus influenzae) bacterial strains, it is currently undergoing clinical trials. An earlier docking study of 7 by Shaw et al. [47] postulated an increased potency mediated by additional interactions between the ribosomal active site and the pyridine and tetrazole rings from 7

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

• Pseudoalteromonas sp. SANK 73390 [54], which exhibits antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA) [55]. Particularly interesting results of feeding experiments with [1,2-13C2]-, [2-13C]- and [1-13C,18O2]acetate were the unexpectedly low incorporation into C-5’ to C-8’ of the

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• antimicrobial and cytotoxic lead structures. Cholesterol conjugate VI (Figure 1) arose from this consideration to be more active than ampicillin against the Gram-negative bacterial strain Escherichia coli (ATCC 11775) and the Gram-positive bacterial strain Staphylococcus aureus (ATTC 12600), while its

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

• tested compounds the most active was diosgenyl 2-deoxy-2-ethylamino-β-D-glucopyranoside (9) with MIC of 0.5, 1, 2, and 8 μg/mL against Staphylococcus epidermidis, Enterococcus faecalis, Staphylococcus aureus, and Rhodococcus equi, respectively. Also the N-propyl derivative 11 was found to be active

• against Enterococcus faecalis, Staphylococcus epidermidis, and Staphylococcus aureus with MIC of 1, 1, and 8 μg/mL, respectively. Importantly, both 9 and 11 exhibit a stronger inhibitory effectivity than diosgenyl 2-deoxy-2-amino-β-D-glucopyranoside hydrochloride (7·HCl), which was found to be very active

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• ) structures [101], the presence of a 1-phenyl or 12-phenyl substituent on 2,3,8,9-tetramethoxy-5-ethylbenzo[c]phenanthridinium chloride [102] significantly enhances the antibacterial (Staphylococcus aureus and Enterococcus faecalis) activity relative to sanguinarine. Another example, using the strategy of

Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

• Véronique Nardello-Rataj and
• Loïc Leclercq

Beilstein J. Org. Chem. 2014, 10, 2603–2622, doi:10.3762/bjoc.10.273

• -hydroxybenzoate, benzyl alcohol, 2-phenoxyethanol) [45]. The authors established a clear relationship between the binding constants and the antimicrobial activity of the preservatives on various strains: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and C. albicans. Indeed, highly water-soluble

A new approach for the synthesis of bisindoles through AgOTf as catalyst

• Jorge Beltrá,
• M. Concepción Gimeno and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2014, 10, 2206–2214, doi:10.3762/bjoc.10.228

• the synthesis of the interesting compound vibrindole A (Scheme 2), an isolated metabolite of the marine bacteria Vibrio parahaemolyticus, which is active against Bacillus subtilis, Staphylococcus aureus and Staphylococcus albus as has been previously demonstrated [43]. In order to prevent the loss of

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

• tricyclic intermediate 121. Cleavage of the TBS ethers and hydrogenolysis of the benzyl ester in presence of amidine 122 yielded trinem 23a as its amidinium salt 123. Trinem 123 exhibited antibacterial activity against a variety of strains, with MIC’s of 1.0 μg/mL against Staphylococcus aureus 853E and 0.1

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

• . Antimicrobial testing against four Gram-positive bacteria (Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, and Streptomyces lividans), one Gram-negative bacterium (Escherichia coli), two yeasts (Candida albicans and Saccharomyces cerevisiae), and two fungi (Aspergillus oryzae and Penicillum

• the growth of Gram-positive bacteria (Micrococcus luteus, Streptomyces lividans, Staphylococcus aureus, Bacillus subtilis), a yeast (Saccharomyces cerevisiae) and a fungus (Penicillium chrysogenum) (Table 2). Moreover, 1 was cytotoxic to 3Y1 rat fibroblasts (GI50 4.5 μM). Under microscopic observation

• strains were grown on agar media (Staphylococcus aureus FDA209P JC-1, Micrococcus luteus ATCC9341, Escherichia coli NIHJ JC-2, Saccharomyces cerevisiae S100, and Candida albicans A9540) or in Sabouraud broth (Penicillum chrysogenum NBRC4626, Streptomyces lividans TK23) overnight and then diluted with

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 Gram-positive Staphylococcus aureus 8325 and the Gram-negative Vibrio anguillarum 90-11-287 (Table 1). These organisms were selected for our bioactivity tests, because S. aureus is a clinically important human pathogen and strains with resistances against multiple antibiotic drugs cause severe

• . All synthetic compounds were used in bioactivity tests towards two bacterial strains, Staphylococcus aureus 8325 [22] and Vibrio anguillarum 90-11-287 [23] (Table 1). The two strains were grown as precultures overnight with agitation at 25 °C in 20 mL cation-adjusted Mueller Hinton II Broth (Cat. No

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

• near Heron Island, Queensland, Australia (Figure 1) [1]. As first in class examples of natural products featuring a 2-nitropyrrole, further elaborated by a farnesyl side chain, the heronapyrroles exhibited promising antibacterial activity against Staphylococcus aureus (ATCC 2593 and 9144) and Bacillus

• 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

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

• natural product and synthetic precursor of 193 shows strong antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA, MIC = 84 nM) and vancomycin-resistant Enterococcus (VRE, MIC = 178 nM) [148]. The structural similarity between pestalachloride A (193) and pestalone (192), which both

• : Lactonamycin (215) and lactonamycin Z (217) were isolated from Streptomyces rishiriensis and Streptomyces anglieri in 1996 and 2003 [157][158]. Both compounds are potent antibacterial agents against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant

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

• ). Antibacterial activity The antibiotic activities of tetramates 2a–h and 3a–f along with analogues 1c and 1d (reported by Novartis [8]) were determined against 4 species of Gram-positive bacteria, consisting of 4 strains of Staphylococcus aureus, including a methicillin-resistant strain (MRSA, S2), vancomycin

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

• (Candida albicans) nor on molds (Mucor hiemalis, Fusarium oxysporum, Alternaria alternata). The natural compound 4 was one of the most active compounds, but also shorter chain analogues 9 and 10 inhibited, for instance, the growth of Staphylococcus aureus at concentrations in the low µg/mL range, whereas

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• ribonucleic acid polymerase. These compounds inhibit chain initiation of RNA synthesis in Staphylococcus aureus, a particularly infectious bacterial strain with reported drug resistance to the antibiotics vancomycin and methicillin [3]. Ripostatin A exists as an equilibrium mixture of ketone and hemiketal

Multivalent display of the antimicrobial peptides BP100 and BP143

• Imma Güell,
• Rafael Ferre,
• Kasper K. Sørensen,
• Esther Badosa,
• Iteng Ng-Choi,
• Emilio Montesinos,
• Eduard Bardají,
• Lidia Feliu,
• Knud J. Jensen and
• Marta Planas

Beilstein J. Org. Chem. 2012, 8, 2106–2117, doi:10.3762/bjoc.8.237

• phytopathogenic bacteria Erwinia amylovora, Xanthomonas axonopodis pv. vesicatoria, and Pseudomonas syringae pv. syringae, and of human pathogenic bacteria Escherichia coli, Staphylococcus aureus, Lysteria monocytogenes, and Salmonella enterica at 0.6, 1.2, 2.5, 5, 7.5, 10 and 20 μM (Table 1). The antibacterial

• , Staphylococcus aureus subsp. aureus ATCC 9144 and Salmonella enterica subsp. enterica LT2 ATCC 15277. All bacteria were stored in Luria Bertani (LB) broth except for L. monocytogenes, which was stored in Brain Heart Infusion (BHI) broth (Oxoid, Hampshire, United Kingdom) supplemented with glycerol (20%) and

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

• running dry [1]. For example, the number of methicillin-resistant Staphylococcus aureus (MRSA) infections in hospitals are still very high and new infectious agents like Acinetobacter baumannii are on the rise, both leading to increased numbers of mortality. In view of this, the discovery of host-defense

• in Table 2) The minimal inhibitory concentrations (MIC) were tested against Escherichia coli DSM 30083, Acinetobacter baumannii DSM 30007, Pseudomonas aeruginosa DSM 50071, Bacillus subtilis DSM 402, Staphylococcus aureus DSM 20231 (type strain), and Staphylococcus aureus ATCC 43300 (MRSA) in a

A macrolactonization approach to the total synthesis of the antimicrobial cyclic depsipeptide LI-F04a and diastereoisomeric analogues

• James R. Cochrane,
• Dong Hee Yoon,
• Christopher S. P. McErlean and
• Katrina A. Jolliffe

Beilstein J. Org. Chem. 2012, 8, 1344–1351, doi:10.3762/bjoc.8.154

• strains of Bacillus (Paenebacillus) and exhibit antifungal and antibacterial activity against a range of clinically relevant species, including Candida albicans, Cryptococcus neoformans, Staphylococcus aureus and Micrococcus luteus [1][2][3][4][5][6][7]. These compounds have a cyclic hexadepsipeptide core

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

• -terminal amino acid component, is described. Moderate to good activity was seen against Gram-positive bacteria in vitro. One cyclohexyl-substituted compound 2c was tested more widely and showed good potency (MIC values ranging from 2–4 μg/mL) against antibiotic-resistant strains of Staphylococcus aureus

• salts 2a–g were tested against the Gram-positive bacteria Staphylococcus aureus (ATCC 6538) and four clinical isolates of vancomycin-resistant (and sensitive) enterococci (VRE; Enterococcus faecium), and the results are shown in Table 1; some compounds were also tested against Staphylococcus epidermidis

• % pure. Determination of minimum inhibitory concentration (MIC) MIC studies (Table 1) were performed on Staphylococcus aureus wild type (ATCC 6538P), and Staphylococcus epidermidis (ATCC 12228) in Mueller–Hinton broth (Oxoid Ltd, England) supplemented with 50 mg/L CaCl2. As in [6], MIC determinations for