Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• last century [2]. The compounds have demonstrated potent antifungal activity [3], and acted as α-adrenoceptor blockers, antagonists of the serotonergic receptor and/or actomyosin ATPase activators [23][24][25]. As shown in Figure 1 for the most prominent representatives, manzacidins A (1) and C (2

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

• strain Na a174, is supposed to be a result of degradation processes due to long-time cultivation. Additionally, the known compound 1,6-dihydroxyphenazin (19) and its arabinofuranoside 20 were obtained. To date, 14 has shown marginal antifungal activity towards Mucor hiemalis (DSM 2656, MIC: 33.3 μg/mL

• testing, revealed that the lactone moiety and the configuration of the methoxyacrylate partial structure are crucial for antifungal activity. The latter structural motif is well known from a range of antifungal compounds produced by fungi and myxobacteria, e.g., the strobilurins and the melithiazols [67

Biosynthesis of α-pyrones

• Till F. Schäberle

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

• (29) showed antifungal activity against Rhizoctonia cerealis, Gaeumannomyces graminis and Botrytis cinerea (Figure 6) [34]. The structural related trichopyrone (30) instead showed no antimicrobial activity [35]. For compound 29 it was further revealed that it represents the prominent headspace

• kill their prey [45][46]. Fusapyrone (32) and the derivative deoxyfusapyrone (33) had been isolated from Fusarium semitectum [39]. These compounds show considerable antifungal activity, e.g., a minimum inhibitory concentration against Botrytis cinerea, Aspergillus parasiticus, and Penicillium brevi

• been used against skin diseases due to its mutagenic effect [71]. Bacterial monobenzo-α-pyrones were isolated from the myxobacterium Stigmatella aurantiaca MYX-030. Myxocoumarins A (65) and B (66) were identified, and 65 was tested for antifungal activity [72]. It showed a promising activity against

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

• an additional chlorine and/or hydroxy substituent. In contrast to dentigerumycin, gerumycins do not exhibit significant antifungal activity in vitro against dentigerumycin-sensitive Escovopsis strains. A detailed biosynthetic analysis of gerumycins revealed that the biosynthetic gene clusters are

• microtermolides A (16) and B (17) (Figure 6), products by an unusual hybrid non-ribosomal–polyketide pathway [95]. In a follow-up study, a Streptomyces isolate with exceptional high antifungal activity was investigated, and an unusual geldanamycin-derived natalamycin A (18), 19-S-methylgeldanamycin (19), and a

• (e.g., bafilomycin A1 (21) and B1 (22), Figure 7), but also a novel polyunsaturated and polyoxygenated 26-membered macrolactam named sceliphrolactam (23) (Figure 7) [101]. Sceliphrolactam showed strong antifungal activity against amphotericin B-resistant Candida albicans, but its functional role in

2-Hetaryl-1,3-tropolones based on five-membered nitrogen heterocycles: synthesis, structure and properties

• Yury A. Sayapin,
• Inna O. Tupaeva,
• Alexandra A. Kolodina,
• Eugeny A. Gusakov,
• Vitaly N. Komissarov,
• Igor V. Dorogan,
• Nadezhda I. Makarova,
• Anatoly V. Metelitsa,
• Valery V. Tkachev,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2015, 11, 2179–2188, doi:10.3762/bjoc.11.236

• -1,2-tropolone) isolated from Chamacyparis taiwanensis possesses antimicrobial and antifungal activity [4][5][6], pronounced insecticidal properties [7][8], and the capability of inhibiting the growth of plants [9]. It also exerts a cytotoxic effect on tumor cells [10] and serves as a potent inhibitor

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

• that were as active as ampicillin. However, conjugate VI from the previous investigation was still more active than these conjugates [24]. The antifungal activity of selected newly synthesized chalcone conjugates was evaluated in vitro against A. flavus (Link) and Candida albicans (ATCC 7102) similarly

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

• alkaloids such as meridine (56) that are found to exert its antifungal activity via the inhibition of nucleic acid biosynthesis [87]. Petrosamine B (99), isolated from the sponge Oceanapia sp., inhibited the Helicobacter pylori enzyme aspartyl semialdehyde dehydrogenase explaining it as an antibacterial

Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3

• Zhi Kai Guo,
• Rong Wang,
• Wei Huang,
• Xiao Nian Li,
• Rong Jiang,
• Ren Xiang Tan and
• Hui Ming Ge

Beilstein J. Org. Chem. 2014, 10, 2677–2682, doi:10.3762/bjoc.10.282

• , Alternaria solani Jones et Grout, Sclerotinia sclerotiorum de Bary, Fusarium graminearum Schw., Fusarium coeruleum Sacc., and Botrytis cinerea Pers.) were tested. Aspergiloid I (1) showed no antibacterial or antifungal activity at a concentration of 20 μg/mL. It also had no antifungal activity against

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

• higher compared to the unmodified one (up to 8.2-fold). As expected, the antifungal activity against C. albicans was enhanced for the MCT-β-CD grafted textile impregnated with miconazole nitrate. The finished fabric retains its antibacterial property even after ten washes unlike the unmodified textile

• mechanism described in Scheme 6. In 2012, the same group reported on the antifungal activity of CD–didecyldimethylammonium chloride inclusion complexes against C. albicans [74]. In this work, the biocidal mechanism was confirmed in vitro by monitoring the mean colony count data, the uncomplexed

• absorption is significantly increased. In other words, the rate of absorption is accelerated because of bioavailability improvement. In 2002, Schirra et al. reported on the inclusion of 1-[2-(allyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole (named enilconazole, see Figure 2) in the β-CD and the antifungal

De novo macrolide–glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

• Richard T. Desmond,
• Anniefer N. Magpusao,
• Chris Lorenc,
• Jeremy B. Alverson,
• Nigel Priestley and
• Mark W. Peczuh

Beilstein J. Org. Chem. 2014, 10, 2215–2221, doi:10.3762/bjoc.10.229

• part of ester linkages; in 4 they are a carbamate and ether, respectively. Modest antifungal activity against C. neoformans and A. fumigatis were also noted for 4 [13]. Here we report on two new natural product-like 12-membered ring macrolides 5 and 6 (Scheme 1) where the pyranose is fused to the

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

• chrysogenum) revealed that all these layers varied in the extent of activity against certain test organism(s). Especially intriguing was the antifungal activity exhibited by the n-hexane-soluble fraction, which, in most cases, comprises lipids. To identify the responsible constituent, the fraction was

• fractionation scheme used at the initial antimicrobial screening. The aqueous 90% MeOH fraction of the raw sample exhibited significant antifungal activity (12 mm/6 mm Φ disk) against Penicillium chrysogenum at 200 μg/disk and an intense molecular ion of 1 at m/z 307 [M – H]− in negative mode LC–MS analysis

• fact, by boiling the alga in 3% aqueous NaHCO3 for 1 min prior to extraction, the antifungal activity and a peak for 1 in the LC–MS analysis completely disappeared (Figure 4). Although the exact degradation pathway of 1 was not identified during this treatment, a facile deactivation of 1 in the raw

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

• 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

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• described in this work. These compounds comprise an unusual structural framework and exhibit remarkable antifungal properties. Keywords: antifungal activity; myxobacteria; natural products; Stigmatella aurantiaca; structure elucidation; Introduction Despite declining interest of most big R&D-driven

• ) data. Taken together these results indicated the presence of the known antifungal myxobacterial compound myxothiazole A (5), as well as the aurachins A (6) and C in the extract. In addition to these metabolites, a series of non-polar compounds exhibiting strong antifungal activity was detected

• Magnaporthe grisea and Phaeosphaeria nodorum at 67 mg/L. Partial effects were found against Blumeria graminis (67 mg/L). The compound was, however, inactive against Drechslera teres and Phytophthora infestans. These findings indicate a broad range antifungal activity of 7, comparable to commercial standard

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• bioactivity of 5-fluoroantimycins and reported they retained potent antifungal activity against Candida albicans, but were significantly reduced in cytotoxity in a leukemia P388 mouse cell line compared to the parent compounds [25]. Sandy et al. recently showed AntB can accept both acyl-CoAs and acyl-SNACs to

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

• trichlorocarbinol ester. A first biological evaluation showed that 204 displays antifungal activity. However, only 90 µg could be isolated and further biological screening was not possible [151]. Several sponge-derived macrolides have proven to be effective cytotoxic agents [152][153] and one could speculate that

ML212: A small-molecule probe for investigating fluconazole resistance mechanisms in Candida albicans

• Willmen Youngsaye,
• Cathy L. Hartland,
• Barbara J. Morgan,
• Amal Ting,
• Partha P. Nag,
• Benjamin Vincent,
• Carrie A. Mosher,
• Joshua A. Bittker,
• Sivaraman Dandapani,
• Michelle Palmer,
• Luke Whitesell,
• Susan Lindquist,
• Stuart L. Schreiber and
• Benito Munoz

Beilstein J. Org. Chem. 2013, 9, 1501–1507, doi:10.3762/bjoc.9.171

• -8 strain. Secondary assay 2 eliminated anything with inherently antifungal activity. These three assays cooperatively removed almost 80% of the original hits, leaving 350 candidates. A final assay (secondary assay 3) was incorporated to discard any compound displaying toxicity to mammalian

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

• bacteria and yeasts we used the agar diffusion test (Table 4) in order to select the most promising compounds for further determination of minimal inhibitory concentrations (MICs) by the broth dilution method (Table 5). In turn, the antifungal activity was tested by the agar dilution method. The results

• 5). Moreover, the chemical nature of the cationic head group influenced the overall toxicity of the CILs, which is in good agreement with several previous studies [60]. The imidazolium CILs exhibited visibly stronger antibacterial and antifungal activity than triazolium CILs (Tables 4–6). However

• , the filamentous fungi displayed high tolerance towards the tested CILs. Nevertheless, the relation between the alkyl chain substituent and the antifungal activity of the tested compounds could still be observed, with the strongest toxicity demonstrated by CILs with an alkyl chain substituent of 12

Theoretical study on β-cyclodextrin inclusion complexes with propiconazole and protonated propiconazole

• Adrian Fifere,
• Narcisa Marangoci,
• Stelian Maier,
• Adina Coroaba,
• Dan Maftei and
• Mariana Pinteala

Beilstein J. Org. Chem. 2012, 8, 2191–2201, doi:10.3762/bjoc.8.247

• fungicide and, lately, for its fungistatic action. Propiconazole nitrate was tested in order to reduce the toxicity of the unmodified PP, but little information is available on this topic. Recently synthesized positively charged protonated propiconazole (PPH+) showed an increased antifungal activity

• compared to unmodified PP. The inclusion compound based on β-cyclodextrin (β-CD) and PPH+ (further abbreviated as β-CD/PPH+) was preliminarily investigated in vitro, and its antifungal activity was reported [4]. Cyclodextrins (CDs) are macrocyclic oligosaccharides consisting of six to twelve glucopyranose

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

• [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

Reactions of nitroxides XIII: Synthesis of the Morita–Baylis–Hillman adducts bearing a nitroxyl moiety using 4-acryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl as a starting compound, and DABCO and quinuclidine as catalysts

• Jerzy Zakrzewski

Beilstein J. Org. Chem. 2012, 8, 1515–1522, doi:10.3762/bjoc.8.171

• consistent with the spectra of the typical series of the MBH adducts of common aldehydes and methyl acrylate, presented in [32]. Synthesized compounds 5a–o showed a weak antifungal activity. No insecticidal, acaricidal and herbicidal activity were shown. Conclusion In conclusion, it has been demonstrated

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

• naturally occurring cyclic peptide may be required for the antifungal activity of this natural product. Keywords: antifungal; cyclic depsipeptide; epimerization; lipopeptide; macrolactonization; peptides; Introduction The LI-F or fusaricidin class of cyclic depsipeptides are produced by a number of

• core through the nitrogen atom of the L-Thr residue. There has been recent interest in the synthesis of the LI-F family of cyclic depsipeptides due to their antifungal activity. Biosynthetic processes have been employed to this end, although these provide mixtures of depsipeptides, which makes it

• precursors. We report here our optimization of these macrolactonization conditions, together with the synthesis of several analogues of LI-F04a using this approach, and an investigation of the antifungal activity of these synthetic lipodepsipeptides. Results and Discussion The required linear precursor for

Triterpenoid saponins from the roots of Acanthophyllum gypsophiloides Regel

• Elena A. Khatuntseva,
• Vladimir M. Men’shov,
• Alexander S. Shashkov,
• Yury E. Tsvetkov,
• Rodion N. Stepanenko,
• Raymonda Ya. Vlasenko,
• Elvira E. Shults,
• Genrikh A. Tolstikov,
• Tatjana G. Tolstikova,
• Dimitri S. Baev,
• Vasiliy A. Kaledin,
• Nelli A. Popova,
• Valeriy P. Nikolin,
• Pavel P. Laktionov,
• Anna V. Cherepanova,
• Tatiana V. Kulakovskaya,
• Ekaterina V. Kulakovskaya and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2012, 8, 763–775, doi:10.3762/bjoc.8.87

• obtained saponins were elucidated by a combination of mass spectrometry and 2D NMR spectroscopy. A study of acute toxicity, hemolytic, anti-inflammatory, immunoadjuvant and antifungal activity was carried out. Both saponins 1 and 2 were shown to exhibit immunoadjuvant properties within the vaccine

• : Basidiomycetous yeasts Cryptococcus terreus, Filobasidiella neoformans, and ascomycetous yeasts Saccharomyces cerevisiae and Саndida albicans. The data in Table 7 demonstrate that compounds 1 and 2 exhibit antifungal activity against both ascomycetous and basidiomycetous yeasts, including the medically important

• C. albicans and F. neoformans. Saponins are known to be more effective against basidiomycetous yeast and at acidic pH act similarly to natural detergents, such as cellobiose lipids [27]. Growth inhibition experiments showed (Figure 6, Table 7), that the lower pH 4.0 favored antifungal activity of

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

• by microorganisms or herbivores and provide a constitutive barrier. Antimicrobial properties Antifungal activity of biphenyls and dibenzofurans was demonstrated in a number of studies [4][7][8][9][10][12][13][14][15][18][19][21]. Spore germination, germ-tube development, and mycelial growth were

• ) were tested for their inhibitory effect on the scab-causing fungus, Venturia inaequalis, the aglycone exhibited significantly stronger antifungal activity than the glucoside [10]. This finding agrees with the observation that the accumulated phytoalexins are commonly aglycones of biphenyls and

• did [12], whereas the opposite tendency was observed for antifungal activity [26]. However, more biphenyls and dibenzofurans need to be tested for their antibacterial and antifungal potentials in order to allow for reliable conclusions concerning structure–activity relationships. The array of

Synthesis of szentiamide, a depsipeptide from entomopathogenic Xenorhabdus szentirmaii with activity against Plasmodium falciparum

• Friederike I. Nollmann,
• Andrea Dowling,
• Marcel Kaiser,
• Klaus Deckmann,
• Sabine Grösch,
• Richard ffrench-Constant and
• Helge B. Bode

Beilstein J. Org. Chem. 2012, 8, 528–533, doi:10.3762/bjoc.8.60

• different Gram-positive (Micrococcus luteus, Bacillus subtilis, Staphylococcus aureus) and Gram-negative (Escherichia coli, Pseudomonas aeroginosa) bacteria, as well as yeast (Candida albicans, Saccharomyces cerivisiae). However, consistent with the published data [12], no antibacterial or antifungal

• activity was detected. Additionally, the peptide 1 was tested against several parasites (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, Plasmodium falciparum) being the causative agents of the neglected tropical diseases [18] sleeping sickness, leishmaniasis and malaria

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

• activity against the tested organisms. Compounds 9–11 exhibited comparable activity to ampicillin against the tested bacteria and moderate to weak antifungal activity against the tested organisms. Furthermore, compounds 1–8 showed moderate to weak activities against all the tested bacteria and fungi

• 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