Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• class of antibacterial agents active also against resistant strains. Keywords: antimicrobial activity; multidrug-resistant bacteria; natural products; synthesis; tetramic acid; Introduction The treatment of bacterial infections by antibiotics is widely regarded as one of the major achievements of the

• synthetic strategy for obtaining new natural compound-derived scaffolds endowed with increased antimicrobial activity. Attention was focused on 2,4-pyrrolidinedione derivatives, so-called tetramic acids. As part of our search for new tetramic acid containing scaffolds, we have synthesized the 2,4

• expressing a multidrug-resistant phenotype (average MIC 32 µg/mL on 30 strains tested). The results confirm that the replacement of the 2,3-pyrrolidinedione core with the tetramic acid nucleus leads to an increase of antimicrobial activity even on MDR strains, thus suggesting that the new scaffold can be

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• [9][10]. The two Dec-NH2 analogs designed to fit a leucine zipper (LZ) template [25][26] presented the lowest hemolytic activity against red blood cells and maintained the antimicrobial activity of the parent template molecule vs Gram-positive bacteria, Gram-negative bacteria, and fungi. The authors

• [31]. Hydrophobicity was incorporated into the sequence via the substitution of residues from the wild-type sequence by Leu and Phe. Leu was chosen because a minimal amount of energy is required for it to adopt a helical structure [28], which favors antimicrobial activity, and it occurs at high

• moment, and net positive charge, characteristics that are known to be important for peptide–membrane interactions [10]. Some of these changes decreased the hemolytic activity against human red blood cells of Dec-NH2, reported by Konno et al. [24], and retained the antimicrobial activity described by

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

• Lucky S. Mulwa,
• Rolf Jansen,
• Dimas F. Praditya,
• Kathrin I. Mohr,
• Patrick W. Okanya,
• Joachim Wink,
• Eike Steinmann and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132

• in lanyamycin (1/2). Antimicrobial activity of lanyamycin (1/2). Cytotoxicity test results of lanyamycin (1/2). Supporting Information Supporting Information File 370: Tables of NMR data and figures of the 1H and 13C NMR including the HCV infectivity results showing viability. Funding Information E

• , nematodes, insects, immunosuppressant or with antitumor activities [12][13][14][15]. Therefore, lanyamycin (1/2) was tested in our screening panel against bacteria, fungi, mammalian cell cultures and for antiviral activity against HCV in human liver cells. Lanyamycin (1/2) was analyzed for antimicrobial

• activity against bacteria and fungi and showed moderate antifungal activity in addition to a good inhibition of Micrococcus luteus (Table 3). When lanyamycin (1/2) was evaluated for cytotoxicity against growing primary cell lines, mouse fibroblasts (L929), and human cancer cell lines, nasopharyngeal cells

Two new 2-alkylquinolones, inhibitory to the fish skin ulcer pathogen Tenacibaculum maritimum, produced by a rhizobacterium of the genus Burkholderia sp.

• Dandan Li,
• Naoya Oku,
• Atsumi Hasada,
• Masafumi Shimizu and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2018, 14, 1446–1451, doi:10.3762/bjoc.14.122

• (23,200); IR ν max (ATR) cm−1: 2923, 2853, 1730, 1635, 1593, 1554, 1500, 1471, 1443, 1354, 1320, 1247, 1137, 1028, 965, 836, 759, 672; HRESIMS–TOF (m/z): [M + H]+ calcd for C18H24NO, 270.18524; found, 270.1855. Evaluation of antimicrobial activity The antibacterial and antifungal activity of 1–8 was

• ) correlations for 3. Referential 13C chemical shifts of an allylic carbon in burkholone [14] and haplacutine F [15]. NMR data for (E)-2-(non-2-en-1-yl)quinolin-4(1H)-one (3) in CDCl3 (δ in ppm). Antimicrobial activity of 1–8 evaluated at 10 μg on Ø 6 mm-paper disc. Supporting Information Supporting Information

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• shown to bind A·T-rich regions preferentially. The compounds containing branched N-alkylpyrrole, hydrophobic N-terminal amide, and especially C-isopropylthiazole (thiazotropsin A as shown in the Figure 4) showed significant antimicrobial activity against MRSA and Candida albicans strains. Thiazotropsin

• group, was found to be extremely potent (MIC values in the range of 0.5–13 μg mL−1) against several strains of S. aureus, both methicillin-sensitive and resistant strains. High antimicrobial activity, shown by this drug, was due to the presence of a hydrophobic head group with a hydrogen-bonding

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

• Thanh-Tuân Bui,
• Fabrice Goubard,
• Malika Ibrahim-Ouali,
• Didier Gigmes and
• Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

• applications of phenoxathiin dioxide ranged from antimicrobial activity [67] to the use as inhibitor for Hepatitis C virus infection [68]. Here, in the context of OLEDs, Lee et al. reported two blue TADF emitters, P1 and P2 (see Figure 10), containing a phenoxaphosphine oxide or a phenoxathiin dioxide acceptor

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• -4-chromanone (12) and 5-hydroxy-2-methyl-4-chromanone (13) were tentatively identified from their mass spectra. Compound 13, which exhibits antimicrobial activity, was previously isolated from various species of Daldinia [16][19][20][21][22] and several endophytic fungi, the latter of which have

• -pyrone 17 exhibited a moderate antifungal and weak antibacterial effect, while the lactone 9 was moderately cytotoxic, but devoid of significant antimicrobial activity. The chlorinated aromatic compound 14 only weakly inhibited the sensitive test organisms Chromobacterium violaceum and Mucor hiemalis

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• in E-configuration. The obtained compounds, particularly the derivative containing a carboxylic group in ortho position of the aromatic ring, exhibited antimicrobial activity [37]. 2. Vinylphosphonium salts in organic synthesis 2.1. Vinylphosphonium salts in the intermolecular Wittig reaction

Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines

• Elisandra Scapin,
• Paulo R. S. Salbego,
• Caroline R. Bender,
• Alexandre R. Meyer,
• Anderson B. Pagliari,
• Tainára Orlando,
• Geórgia C. Zimmer,
• Clarissa P. Frizzo,
• Helio G. Bonacorso,
• Nilo Zanatta and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 2396–2407, doi:10.3762/bjoc.13.237

• , our research group demonstrated a highly regioselective synthesis of a series of trifluoromethylated tetrazolo[1,5-a]pyrimidines with potent antimicrobial activity [37]. The reaction between several β-alkoxyvinyl trifluoromethyl ketones [CF3C(O)CH=C(R)OCH3] (in which R = Ph, 4-F–C6H4, 4-Cl–C6H4, 4-Br

Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity

• Henryk Myszka,
• Patrycja Sokołowska,
• Agnieszka Cieślińska,
• Andrzej Nowacki,
• Maciej Jaśkiewicz,
• Wojciech Kamysz and
• Beata Liberek

Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227

• antimicrobial activity the N-acyl (6, 7), 2-ureido (8–10), N-monoalkyl (11) and N,N-dialkyl (12, 13) derivatives of diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside were also synthesized (Figure 1). The N-acetyl derivative 6 was obtained by the treatment of 4 with acetic anhydride in methanol with Et3N whereas N

• as well as the HRMS spectrometry confirmed the structures of 11–13 (see Supporting Information File 1 for experimental and NMR data). Evaluation of antimicrobial activity The antimicrobial in vitro activities of 5–13 were tested against two fungal strains: Candida albicans and Candida tropicalis, and

• -deoxy-β-D-galactopyranoside (9) exhibits a good activity against all the tested pathogens with MICs of 8–64 µg/mL, whereas 8 was effective against C. tropicalis and E. faecium only and compound 10 does not exhibit any antimicrobial activity. Among the presented saponins, N-ethyl derivative 11 exhibits

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• endothelial cells [86], while T cells [87][88] and macrophages [80][89] are less sensitive. Strikingly, no toxic potential was observed against human hepatoma HuH7 or human embryonic kidney HEK293 T cells [85]. Intriguingly, mycolactone A/B lacks antimicrobial activity [90], which suggests that the defense

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• family which were isolated from several strains of Paenibacillus polymyxa [3][4]. Fusaricidins exhibit antimicrobial activity against Gram-positive bacteria and a wide range of fungi including Leptosphaeria maculans, a plant pathogenic fungus responsible for the blackleg disease on Brassica crops [5][6

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

• Juraj Dobiaš,
• Marek Ondruš,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2017, 13, 1350–1360, doi:10.3762/bjoc.13.132

• have described similar biological activities to the parent quinoxalin-2(1H)-ones 1. Mashevskaya et al. reported about an antimicrobial activity for compound 6 at 1 mg/mL for S. aureus P-209 and E. coli M17 strains [11]. Several recent studies have identified 3,4-dihydroquinoxalin-2(1H)-ones 7–10 as

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• stereoselective synthesis of (1R,3E,7E,11S,12S)-3,7,18-dolabellatriene, a bicyclic diterpene (Scheme 2). Dollabellanes derive mostly from marine organisms and display bioactivities such as antiviral and cytotoxic effects [59]. Dolabellatriene from a reprogrammed CotB2 contribute with antimicrobial activity

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• moieties may increase or decrease the biological activity. A series of isoxazole fused 1-indanones 64 with increased anti-inflammatory and antimicrobial activity has been synthesized by Giles et al. [46]. In this synthesis, diethyl phthalate (61) was reacted with ethyl acetate to obtain indane-1,3-dione

Biosynthetic origin of butyrolactol A, an antifungal polyketide produced by a marine-derived Streptomyces

• Enjuro Harunari,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2017, 13, 441–450, doi:10.3762/bjoc.13.47

• recently, isolation of butyrolactols C and D was presented but the details are not available in public domains [10]. 1 has a broad antimicrobial activity against fungi ranging from Candida albicans to Trichophyton mentagrophytes with comparative activity to nystatin [9]. Despite the uniqueness of the

Synthesis of acylhydrazino-peptomers, a new class of peptidomimetics, by consecutive Ugi and hydrazino-Ugi reactions

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

Beilstein J. Org. Chem. 2016, 12, 2865–2872, doi:10.3762/bjoc.12.285

• one of the CONH links is replaced by a hydrazido fragment CONHNH, Figure 1) represent another class of peptidomimetics with promising conformational and biological activities, such as protease inhibition [37] and antimicrobial activity [38]. There are some natural peptides that contain such an α

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

• B Enduracidin A (7) and B (8) were first isolated from Streptomyces fungicidicus B 5477 from a soil sample collected in Nishinomiya, Japan (Figure 2) [1]. Detailed reports of the isolation procedures, in vivo and in vitro antimicrobial activity, physical properties and structure elucidation have

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

• Atul A. Dhavan,
• Rahul D. Kaduskar,
• Loana Musso,
• Leonardo Scaglioni,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159

• 17 in 50% yield. Compounds 1 and 17 were subjected to a preliminary study of the antimicrobial activity against Staphylococcus and Escherichia coli (Staphylococcus pseudintermedius [25], 25 strains; Escherichia coli, 20 strains. QC: S. aureus ATCC 25923 and Escherichia coli ATCC 25922 were also used

• unusual 2,3-pyrrolidinedione system and developed a synthetic strategy towards new lead compounds with antimicrobial activity. Efforts to synthesize analogues to build a structure–activity relationship (SAR) profile and optimize the activity are underway. Structure of leopolic acid A. Synthesis of

• analytical data for the reported compounds; antimicrobial activity evaluation procedures. Supporting Information File 462: 1H and 13C NMR spectra of all the new compounds; 2D HMBC, HSQC spectra of compounds 1, and 17, COSY spectrum of compound 1, MIC of compounds 1 and 17 against Staphylococcus

Mutagenic activity of quaternary ammonium salt derivatives of carbohydrates

• Barbara Dmochowska,
• Karol Sikora,
• Anna Woziwodzka,
• Jacek Piosik and
• Beata Podgórska

Beilstein J. Org. Chem. 2016, 12, 1434–1439, doi:10.3762/bjoc.12.138

• and sugar moieties were described before [22][25][26]. It was shown that quaternization of chitosan increases its antimicrobial activity; such polymer is proposed to be used as a wound dressing after surgeries to eliminate infections and to improve the healing process [27][28][29]. Moreover, the

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

• formed by the head-to-tail cyclisation of two nonapeptides that are themselves derived from the C-terminal region of precursor peptides, and both heterodimers or homodimers can be formed in this process [84][144]. Along with their antimicrobial activity, these peptides can inhibit fusion of HIV-1 to host

• human-tissue cultures leads to the production of properly cyclised θ-defensins that possess antimicrobial activity [148], indicating that humans have retained the proteins required for processing and cyclisation. The identity of these genes in either humans or monkeys has not been found, although a

Synthesis, fluorescence properties and the promising cytotoxicity of pyrene–derived aminophosphonates

• Jarosław Lewkowski,
• Maria Rodriguez Moya,
• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Renata Kontek and
• Gabriela Gajek

Beilstein J. Org. Chem. 2016, 12, 1229–1235, doi:10.3762/bjoc.12.117

• properties. This expectation is supported by the biological activity of azomethine derivatives of pyrene-1-carboxaldehyde. They show antimicrobial action, e.g., 1-phenytoinylacetic acid hydrazone of pyrene-1-carboxaldehyde demonstrated a moderate antimicrobial activity towards Escherichia coli and

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

• molecules. Additionally, the siderophore nannochelin A (23) also from other myxobacteria was isolated [50]. All three compounds were tested against a broad range of microorganisms and mammalian cell lines. The most relevant antimicrobial activity was shown by 21 towards Mycobacterium diernhoferi (DSM 43542

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

• , Canberra, Australian Capital Territory, 2601, Australia Medical School, College of Medicine, Biology and Environment, The Australian National University, Canberra, Australian Capital Territory, 2601, Australia 10.3762/bjoc.12.95 Abstract Pantothenamides are known for their in vitro antimicrobial activity

• ]. One successful research direction has been to revisit “older” unexploited structural classes of antimicrobials [2][3][4][5]. As first demonstrated in the 1970s [6], many pantothenamides show antimicrobial activity [7][8][9][10][11][12], including antibacterial, antifungal and/or antiplasmodial

• enzymes, the pantetheinases, that normally hydrolyze pantetheine to pantothenate and cysteamine in human blood [10], which precludes their clinical application. The antimicrobial activity of pantothenamides is believed to arise from at least two mechanisms depending on the microbial strain. In E. coli

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 is also glycosylated in 5'-position with an aminoribose unit, and they contain a fatty acid moiety as well. Caprazamycins also display noteworthy antimicrobial activity against M. tuberculosis as well as most Gram-positive bacteria (Table 1) [46][48]. All aforementioned nucleoside antibiotics

• E. faecalis, but also against some Gram-negative E. coli strains [49]. Tunicamycin, capuramycin and FR-900493 only show antimicrobial activity against Gram-positive strains. For mureidomycin C (R5 = Gly, AA2 = AA5 = m-Tyr, AA4 = Met, B = uracil, see Figure 2) as a representative compound, no