Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• and 1H NMR analysis). Members of this library were claimed to show promising biological activity, however details were not given. Muraymycins (MRYs) are a class of naturally occurring nucleoside-lipopeptide antibiotics with excellent antibacterial activity. Matsuda and coworkers envisaged that MRYs

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

• detection in cultivations of CMB-0423 and finally the evaluation of its antibacterial activity. We thus demonstrate that biosynthetic considerations and the joint effort of synthetic and natural product chemists can result in the identification of new members of a rare class of natural products. Keywords

• 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

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

• ., Bacillus subtilis strain ATCC 11060) and modest activity against fungi (e.g., Fusarium verticillioides strain S68 and Rhizoctonia solani strain GXE4). However, cuevaenes D (4) and E (5) showed no inhibitory activity against any of the tested microbes. Keywords: antibacterial activity; cuevaenes

• for 48 h for antifungal activity and at 37 °C for 24 h for antibacterial activity and examined for the presence of a zone of inhibition. Cuevaenes A–E (1–5) isolated from Streptomyces sp. LZ35. Selected NOESY correlations of compounds 1, 3 and 4, 5. 1H and 13C NMR spectroscopy data for compounds 3, 4

• ; geometrical isomer; natural products; Streptomyces sp. LZ35; Introduction Cuevaenes are polyketides containing 3-hydroxybenzoic acid (3-HBA). Only 4 naturally occurring cuevaenes are described. Cuevaenes A and B were isolated from Streptomyces sp. HKI 0180 fifteen years ago and display moderate antibacterial

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

• Suresh Babu Meruva,
• Akula Raghunadh,
• Raghavendra Rao Kamaraju,
• U. K. Syam Kumar and
• P. K. Dubey

Beilstein J. Org. Chem. 2014, 10, 471–480, doi:10.3762/bjoc.10.45

• antibacterial activity. Eudistomin Y6 (6f) exhibits moderate antibacterial activity against the Gram-positive bacteria Staphylococcus epidermis and Bacillus subtilis. Results and Discussion There are several approaches known in literature for the synthesis of β-carbolines. Most of the syntheses of eudistomin T

Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• semisynthetic urethane derivatives of monensin A show maintained or even improved antibacterial activity [37][38][39]. The recently-determined crystal structure of the C-26-O-phenylurethane of monensin A sodium salt shows that although one of the carboxylate oxygen atoms coordinates the cation, this atom is

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• , antimalarial and antibacterial activity, which are a strong motivation for total synthesis [26][27]. In addition, several ambiguities in the structural assignment of some of these natural products still exist, and chemical synthesis has been proven to be a powerful and reliable tool for completing the

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

• rapid construction, and the evaluation of their antibacterial activity is reported. Keywords: acylation; antibacterial; drug discovery; natural products; tetramate; Introduction The discovery of new antibiotic families with novel modes of action is a promising way to overcome resistant or virulent

• inhibitory activity) [7] and unnatural systems, such as 3-carboxamide tetramic acid 1c and 3-carboxamide piperidine-2,4-dione 1d (undecaprenyl pyrophosphate synthase (UPPS) inhibitory activity) [8] exhibit high levels of antibacterial activity (Figure 1). All these systems share a β-dicarbonyl core. A drug

• . The substituents of system 3 were chosen in order to probe the effect of a C(3) substituent containing a sulfur heteroatom, which we had earlier seen results in enhanced antibacterial activity compared with the oxygen counterpart [10], for two types of amide substituent and a range of C(3

Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions

• Trevor A. Hamlin and
• Nicholas E. Leadbeater

Beilstein J. Org. Chem. 2013, 9, 1843–1852, doi:10.3762/bjoc.9.215

• -ketoesters and aromatic aldehydes to yield dihydropyrimidines has received significant attention, these products having pharmacological activity including calcium channel modulation, mitotic kinesin Eg5 inhibition, and antiviral and antibacterial activity [49][50]. The Biginelli reaction has been performed

Lanostane- and cycloartane-type triterpenoids from Abies balsamea oleoresin

• Serge Lavoie,
• Charles Gauthier,
• Jean Legault,
• Sylvain Mercier,
• Vakhtang Mshvildadze and
• André Pichette

Beilstein J. Org. Chem. 2013, 9, 1333–1339, doi:10.3762/bjoc.9.150

• against human cell lines (A549, DLD-1, WS1) and their antibacterial activity against E. coli and S. aureus. Abiesonic acid (6) exhibited weak cytotoxic activity against A549 (IC50 = 22 µM) while compounds 1 and 4 were weakly active against S. aureus (MIC = 25 µM). Keywords: Abies balsamea; cycloartane

• (WS1) using the resazurin reduction test [25]. Etoposide was used as a positive control (IC50 ≤ 1.0 µM). None of the compounds were found to be active (IC50 > 25 µM) with the exception of abiesonic acid (6), which showed a weak cytotoxic activity against A549 (IC50 = 22 µM). The antibacterial activity

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

• compounds exhibited biological activity that was significantly dependent on the alkyl chain length, with considerably high toxicity of the substituents with 10–16 carbon atoms. The imidazolium salts revealed stronger antibacterial activity than their triazolium analogues. Model for the configurational

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

• -melittin antimicrobial undecapeptide hybrids on a carbohydrate template could provide carbopeptides with improved biological properties. In particular, KKLFKKILKYL-NH2 (BP100) and KKLfKKILKYL-NH2 (BP143) were selected based on their high antibacterial activity against the plant pathogenic bacteria Erwinia

• (BP100) and KKLfKKILKYL-NH2 (BP143), which have been shown to display high antibacterial activity [28][29]. Templates cDTE and Galp functionalized with aminooxyacetic acid were prepared as before [23][30]. Peptide aldehydes KKLFKKILKYLG-H (4) and KKLfKKILKYLG-H (5), derived from BP100 and BP143

• . monocytogenes was scrapped from BHI agar after growing for 24 h at 37 °C. The cell material was suspended in sterile water to obtain a suspension of 108 CFU mL−1. Antibacterial activity As described in [28], lyophilized compounds were solubilized in sterile Milli-Q water to a final concentration of 1000 μM 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

• of small synthetic arginine and tryptophan containing peptides was prepared and analyzed for their antibacterial activity. The effect of N-terminal substitution with metallocenoyl groups such as ferrocene (FcCO) and ruthenocene (RcCO) was investigated. Antibacterial activity in different media

• [14], trivalent lipidated short peptides with antifungal activity [15], peptoids [16], peptides containing D-amino acids [17], and foldamers based on β-amino acid residues with antibacterial activity [18] have been described. Whereas nature has to stick to products compatible with biosynthetic

• derivatives of platensimycin [23][24][25][26][27][28]. Among the synAMPs known to date, those based on arginine (Arg or R) and tryptophan (Trp or W) residues are amongst the smallest peptides that still possess significant antibacterial activity. For example, Strøm et al. [29] described short RW-based synAMPs

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

• assessing the effect of variation in the spatial disposition of the cycloalkyl or oxacycloalkyl ring on antibacterial activity. The conformationally less restricted gem diethyl-substituted compound 2g was also targeted in order to make antibacterial activity comparisons with the five-membered ring analogue

• chain, either on the carboxylic ester side (2e) or the amino side (2f), had no or little effect on antibacterial activity, regardless of whether a ring oxygen atom was present or not. It appeared that moving the hydrophobic ring substituent position by a small amount in the terminal amino acid unit

• 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

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

• , helical structure and phospholipid bilayer interactions [22]. The results obtained with the gp41w-derived peptides reveal a complex relationship between the structural factors that contribute to the antibacterial activity and the features that determine the hemolytic activity. A large proportion of AMPs

Partial thioamide scan on the lipopeptaibiotic trichogin GA IV. Effects on folding and bioactivity

• Marta De Zotti,
• Barbara Biondi,
• Cristina Peggion,
• Matteo De Poli,
• Haleh Fathi,
• Simona Oancea,
• Claudio Toniolo and
• Fernando Formaggio

Beilstein J. Org. Chem. 2012, 8, 1161–1171, doi:10.3762/bjoc.8.129

• vesicles in the absence of peptide, Ft = fluorescence intensity of vesicles at time t in the presence of peptide, and FT = total fluorescence intensity determined by disrupting the vesicles by the addition of 50 μL of a Triton X-100 solution. The experiments were stopped at 20 min. Antibacterial activity

• Peptide antibacterial activity was tested against Gram-positive and Gram-negative bacteria by the standardized disk diffusion Bauer–Kirby method [75] using the Müller–Hinton culture medium at pH 7.2–7.4 as recommended by the National Committee for Clinical Laboratory Standards [76]. The antibacterial

• activity assay was performed in a similar way to that described in reference [77]. The activity of peptides was tested against clinical isolates of bacteria and reference bacterial strains: Staphylococcus aureus American Type Culture Collection strains (ATCC) 25923, Streptococcus pyogenes ATCC 19615

Similarity analysis, synthesis, and bioassay of antibacterial cyclic peptidomimetics

• Workalemahu M. Berhanu,
• Mohamed A. Ibrahim,
• Girinath G. Pillai,
• Alexander A. Oliferenko,
• Levan Khelashvili,
• Farukh Jabeen,
• Bushra Mirza,
• Farzana Latif Ansari,
• Ihsan ul-Haq,
• Said A. El-Feky and
• Alan R. Katritzky

Beilstein J. Org. Chem. 2012, 8, 1146–1160, doi:10.3762/bjoc.8.128

• . Some of the synthesized compounds were tested against an array of microorganisms and showed antibacterial activity against Bordetella bronchistepica, Micrococcus luteus, and Salmonella typhimurium. Keywords: antibacterial; cluster analysis; N-acylbenzotriazoles; peptidomimetics; similarity

• activity, with compounds 24 and 27 being the most active. The side-chain substitution clearly controls the antibacterial activity, as the cyclic scaffold is identical. The 18-membered ring scaffold 37, accessible through the benzotriazole route, provides an excellent opportunity for introducing

• bis(S-acylcysteine) 36 forming the pyridine–cysteine-containing macrocycle 40 in 70% yield (Scheme 3, see Supporting Information File 1 for experimental details). Bioassay Screening for antibacterial activity was performed for two cyclic peptidomimetics belonging to scaffold 37, namely 37a and 37b

Asymmetric total synthesis of smyrindiol employing an organocatalytic aldol key step

• Dieter Enders,
• Jeanne Fronert,
• Tom Bisschops and
• Florian Boeck

Beilstein J. Org. Chem. 2012, 8, 1112–1117, doi:10.3762/bjoc.8.123

• used in the treatment of vitiligo, psoriasis and other skin diseases [3]. Some furocoumarins exhibit vasodilatory, antifungal and antibacterial activity [4][5]. Smyrindiol (1), also called (+)-(2’S,3’R)-3-hydroxymarmesin [7], is a linear dihydrofurocoumarin, which was isolated from the roots of

Chemistry of polyhalogenated nitrobutadienes, 10: Synthesis of highly functionalized heterocycles with a rigid 6-amino-3-azabicyclo[3.1.0]hexane moiety

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Armin de Meijere and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2012, 8, 621–628, doi:10.3762/bjoc.8.69

• (Scheme 5). These amides 20 and 21 are hot candidates for biological testing, as some known amides of 4-chloroisothiazol-3-carboxylic acid have been shown to exhibit high antibacterial activity [25][26][27]. The high number of heteroatoms in 20 and 21, accompanied by only a few hydrogen atoms, requires 1H

Phytoalexins of the Pyrinae: Biphenyls and dibenzofurans

• Cornelia Chizzali and
• Ludger Beerhues

Beilstein J. Org. Chem. 2012, 8, 613–620, doi:10.3762/bjoc.8.68

• dibenzofurans. The antibacterial activity of biphenyls and dibenzofurans is less well studied [24][25]. Recently, a number of the Pyrinae-specific phytoalexins were tested for in vitro antibacterial activity against E. amylovora, the fire-blight-causing agent [12]. 3,5-Dihydroxybiphenyl was the most active

• compound with a minimum inhibitory concentration (MIC) of 115 μg/mL. While this concentration was bactericidal, a concentration approximately ten times lower led to 50% growth inhibition (MIC50 = 17 μg/mL). Biphenyls exhibited somewhat stronger antibacterial activity than structurally related dibenzofurans

Mutational analysis of a phenazine biosynthetic gene cluster in Streptomyces anulatus 9663

• Orwah Saleh,
• Katrin Flinspach,
• Lucia Westrich,
• Andreas Kulik,
• Bertolt Gust,
• Hans-Peter Fiedler and
• Lutz Heide

Beilstein J. Org. Chem. 2012, 8, 501–513, doi:10.3762/bjoc.8.57

• as = +16.8 (c = 0.33, MeOH). Endophenazine E is a new natural product. The conjugation of a phenazine to N-acetylcysteine has been described previously [17]. In that case, conjugation occurred through the thiol group of cysteine and led to the loss of the antibacterial activity of the phenazine. A

Carbamate derivatives and sesquiterpenoids from the South China Sea gorgonian Melitodes squamata

• Li-Si Huang,
• Fei He,
• Hui Huang,
• Xiao-Yong Zhang and
• Shu-Hua Qi

Beilstein J. Org. Chem. 2012, 8, 170–176, doi:10.3762/bjoc.8.18

• rarely found in marine natural compounds, and 7 showed moderate antibacterial activity. The possible biosynthesis routes of 1–5 were conjectured. Keywords: carbamate; gorgonian; Melitodes squamata; sesquiterpenoid; Introduction Gorgonians are recognized to mainly produce acetogenins, sesquiterpenoids

• 1, 2, 6, and 7 have not been previously reported. The cytotoxicity of 1–9 against human malignant melanoma A735 and cervical carcinoma HeLa cell lines, and the antibacterial activity of 1–5 and 7 towards bacteria Escherichia coli, Bacillus subtilis and Micrococcus luteus were evaluated. The possible

• by MTT assay. The results show that 1–9 does not exhibit cytotoxicity against A735 and HeLa cell lines with IC50 > 200 μg/mL. Antibacterial activity of compounds 1–5 at a concentration of 25 μg/disc (diameter 6 mm) was measured against bacteria Escherichia coli, Bacillus subtilis, and Micrococcus

Synthesis and characterization of new diiodocoumarin derivatives with promising antimicrobial activities

• Hany M. Mohamed,
• Ashraf H. F. Abd EL-Wahab,
• Ahmed M. EL-Agrody,
• Ahmed H. Bedair,
• Fathy A. Eid,
• Mostafa M. Khafagy and
• Kamal A. Abd-EL-Rehem

Beilstein J. Org. Chem. 2011, 7, 1688–1696, doi:10.3762/bjoc.7.199

• ampicillin (30 µg mL−1) as the standard antibiotic reference for antibacterial activity, and calforan (30 µg mL−1) was used as a reference antifungal activity. The tested compounds were dissolved in N,N-dimethylformamide (DMF) to give a solution of 1 mg mL−1. The inhibition zones (diameter of the hole) were

• presence of diiodocoumarin-3-carboxamides decreased the antimicrobial activity. Graphical representation of the antibacterial activity of tested compounds compared to ampicillin. Graphical representation of antifungal activity of tested compounds, compared to calforan. Synthesis of 6,8-diiodocoumarin

• structures of all newly synthesized compounds were confirmed by IR, 1H NMR, 13C NMR and mass spectrometry. The inhibitory effects of the synthetic compounds against these organisms are given in Table 1, Figure 1 and Figure 2. Among the series tested, compounds 12–14a,b exhibited excellent antibacterial

Toward an integrated route to the vernonia allenes and related sesquiterpenoids

• Da Xu,
• Michael A. Drahl and
• Lawrence J. Williams

Beilstein J. Org. Chem. 2011, 7, 937–943, doi:10.3762/bjoc.7.104

• promyelocytic leukemia cell line in a dose-dependent manner [26], and ester derivatives of salonitenolide 12 show promising antibacterial activity [27]. We have initiated a study that aims to integrate the chemical syntheses of compounds in this structure space into a single, late-stage-divergent, route [28]. A