Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• antagonists [8], cyclin-dependent kinases GSK-3β, CK1 [9] and nitric oxide synthase activity inhibitors [10][11], as well as antibacterial [2], antifungal [12], antihistamine [13] and antitumor activities [14]. Remarkable immunosuppressive properties are inherent to palau’amine (VI) [15]. Ceratamines XIII are

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• transformations [1]. The cyclopropane subunit is also present in many biologically important compounds such as pheromones, fatty acid metabolites, unusual amino acids and possess interesting herbicidal, insecticidal, antibiotic, antibacterial, antifungal, antiviral and antitumor activities [2]. For these reasons

• are also important precursors in the synthesis of various biologically active molecules and pharmaceuticals such as antidepressants, antiviral and antibacterial drugs [4]. Cyclopropanols and their derivatives are considered to be carbocyclic homologues of enols presenting similar chemical properties

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• benzyl improves the in vitro antistaphylococcal activity. In contrast, the incorporation of smaller heterocycles like pyridine and imidazole as well as isosteric benzimidazole instead of the indole moieties lead to a loss of antibacterial activity. Kennedy et al. could synthesize a 2-phenyl derivative

• that showed nanomolar activity against S. aureus [20]. To the detriment of this compound class, all derivatives lose their antibacterial activity in the presence of serum in vitro in serial broth and agar dilution method [16][20]. Even with the use of charged groups as modifiers, serum-protein binding

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• antibacterial and antiviral. The presence of a carboxamide unit connected to carbon C-3 of the 4-oxoquinoline core has been associated with various biological activities. Experimentally, the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide occurs at the nitrogen of the oxoquinoline

• ; regioselectivity; Introduction Since the discovery of the antibacterial agent nalidixic acid, as a byproduct from the synthesis of chloroquine, the medicinal interest in 4-oxoquinolines as bioactive substances has exponentially grown over the years. Nowadays, some of the most important antibiotics used in the

• treatment of bacterial infections are 4-oxoquinoline derivatives, namely, ciprofloxacin, levofloxacin, lomefloxacin and others [1][2]. Even though the antibacterial profile has been the most common bioactivity associated with this class of substances [1], other types of pharmacological activities have also

A novel and efficient synthesis of phenanthrene derivatives via palladium/norbornadiene-catalyzed domino one-pot reaction

• Yue Zhong,
• Wen-Yu Wu,
• Shao-Peng Yu,
• Tian-Yuan Fan,
• Hai-Tao Yu,
• Nian-Guang Li,
• Zhi-Hao Shi,
• Yu-Ping Tang and
• Jin-Ao Duan

Beilstein J. Org. Chem. 2019, 15, 291–298, doi:10.3762/bjoc.15.26

• ], antibacterial [6], anti-inflammatory [7] and so on. During the past decades, numerous methods for the preparation of phenanthrene derivatives have been developed. In 2003, Gabriel Tojo’s group reported a base-catalyzed photochemical synthesis of phenanthrene derivatives [8] through intramolecular aromatic

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• antibiotic-insensitive strains, the steady decline in the number of new antibacterial drugs and the insufficient investment in antimicrobial research and development (R&D) by the major pharmaceutical companies have led to a global health crisis in which the prospect of a future without a safe and effective

• anti-infective compound is a very real and alarming possibility [5][6]. Consequently, new antibacterial drugs and treatment strategies are urgently needed to tackle the increasing multidrug-resistance in bacteria [7]. To further accelerate antibiotics development numerous approaches have been put in

• pneumoniae, penicillin-non-susceptible Haemophilus influenzae, ampicillin-resistant Shigella spp., fluoroquinolone-resistant Given the prevalence of antibacterial drug-resistant pathogens, one viable and promising strategy to combat these multidrug-resistant bacteria is the development of antibiotic

Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• potent antibacterial activity against Helicobacter pylori and induce growth defects in Escherichia coli and Staphylococcus aureus. Taking inspiration from a methodology used in our total synthesis of natural products, we applied this methodology to access analogues possessing bulky N-substituents

• antibiotics, bacterial signalling and iron metabolism [1]. Structural optimisation of quinolones possessing intriguing properties can lead to the discovery of important drug classes, as demonstrated by the fluoroquinolone antibiotics, which were inspired by the observation of an antibacterial quinolone side

• , and were first isolated by Dekker et al. (1–8, Figure 1) [3]. The authors noted the potent antibacterial activity of these compounds against Helicobacter pylori, which is responsible for the generation of numerous digestive disorders [4]. Furthermore, with the presence of a lipophilic chain in the 2

The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• antibacterial agents. Keywords: NDH-2; phenothiazine; siderophore; siderophore–antibiotic; siderophore conjugate; Introduction One of the biggest challenges facing the modern society is antibiotic resistance and the prospect of current antibiotics becoming near redundant against previously treatable

• other bacterial species [11]. NDH-2 is absent in mammalian cells and similar to PBPs is associated with the bacterial membrane [12]. Considering the significant antibacterial activity of phenothiazines, in particular the anti-TB activity of 1, and their membrane-associated NDH-2 target we hypothesised 1

• linker is attached to a position in 1 such that the antibacterial activity is not compromised. Based on previous structure–activity studies of 1 by Bate et al., whereby a methoxy group was positioned on the para-position of the phenyl ring of 1 without loss of activity, we hypothesised this may be a

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• modes of action that avoid cross-resistance to established drug-resistant strains, the development of antivirulence drugs will address a promising new paradigm in antibacterial therapy, leading to a second anti-infective pillar. It has to be emphasized that a concerted approach to new anti-infectives is

Design and synthesis of C₃-symmetric molecules bearing propellane moieties via cyclotrimerization and a ring-closing metathesis sequence

• Sambasivarao Kotha,
• Saidulu Todeti and
• Vikas R. Aswar

Beilstein J. Org. Chem. 2018, 14, 2537–2544, doi:10.3762/bjoc.14.230

• units in bioactive natural products and pharmaceuticals. Some of these propellanes exhibit intresting properties like antibiotic, antifungal, anticancer, platelet-activating factor antagonistic and antibacterial activities. The propellane skeleton is present in many alkaloids such as aknadinine (1

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

• the plant Juniperus excelsa [3][4]. Leopolic acid A is endowed with antibacterial activity against Staphylococcus aureus and Staphylococcus pseudintermedius with a MIC of 16 μg/mL, and against Escherichia coli with a MIC of 128 µg/mL [3][4]. In terms of structural features, this compound contains a 4

• antibacterial, antiviral, antifungal and anticancer activities [13]. More than one hundred of them have been isolated from a variety of natural sources and numerous analogues have been synthesized and studied for their multiple biological activities [13]. For this reason, we planned the synthesis of a leopolic

Stereoselective total synthesis and structural revision of the diacetylenic diol natural products strongylodiols H and I

• Pamarthi Gangadhar,
• Sayini Ramakrishna,
• Ponneri Venkateswarlu and
• Pabbaraja Srihari

Beilstein J. Org. Chem. 2018, 14, 2313–2320, doi:10.3762/bjoc.14.206

• continue to attract significant interest owing to their structural architectures and impressive biological properties that include antibacterial [3], anticancer [4][5][6], antiviral [7] and neuritogenic activities [8]. Watanabe et al. [9][10] have isolated strongylodiols A–J (1–10, Figure 1) [11] from the

Investigation of the electrophilic reactivity of the biologically active marine sesquiterpenoid onchidal and model compounds

• Melissa M. Cadelis and
• Brent R. Copp

Beilstein J. Org. Chem. 2018, 14, 2229–2235, doi:10.3762/bjoc.14.197

• binneyi) also exhibit biological properties including feeding deterrence, antibacterial and anticholinesterase activities. Chemical reactivity studies using polygodial (1), scalaradial (2) and caulerpenyne (3) have demonstrated evidence of pyrrole formation upon reaction with primary amines, with

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• lasso, a structural motif which was also recently found in nature for peptides with high antibacterial efficacy [71]. In 12, the TTF molecule is not implemented in the thread but in the wheel component. In the neutral state, strong hydrogen bonding between the crown ether wheel and the dialkylammonium

Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium derivatives by Palladium-mediated cross-coupling reactions

• Siva Sankar Murthy Bandaru,
• Darinka Dzubiel,
• Heiko Ihmels,
• Mohebodin Karbasiyoun,
• Mohamed M. A. Mahmoud and
• Carola Schulzke

Beilstein J. Org. Chem. 2018, 14, 1871–1884, doi:10.3762/bjoc.14.161

• ligand may interfere with DNA–enzyme recognition events, which are essential for DNA-based cellular processes, e.g., gene replication or transcription [1]. To this end, it was shown that DNA-binding ligands may operate as chemotherapeutic anticancer, antiviral or antibacterial drugs, for example as

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• starting from substrate 147. (±)-Aculeatin and its derivatives possessing spirocyclic skeleton are known for their antibacterial and antiprotozoal properties [135]. In this report, substrate 147 was cyclized to spiroketals, i.e., (−)-aculeatin (146a) and (+)-146b in 3:2 ratio. Herein, 1.0 equivalent of

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• that calixarenes themselves display antibacterial, antiviral, and anticancer properties [64]. Herein, we describe the synthesis of a multivalent phototherapeutic agent designed in order to specifically target membrane receptors involved in the angiogenesis process. The multivalent system is composed of

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

• inhibited the growth of the marine bacterium Tenacibaculum maritimum, an etiological agent of skin ulcers in marine fish, offering new opportunities to develop antibacterial drugs for fish farming. Keywords: antimicrobial; Burkholderia; quinolone; skin ulcer; Tenacibaculum maritimum; Findings Bacteria of

• , 1 yeast, and 4 fungi. The result of this screening prompted the detailed chemical study of a strain coded as MBAF1239, which resulted in the isolation of eight antibacterial metabolites, including the two new 2-alkylquinolones 1 and 3 (Figure 1). Strain MBAF1239 was seed-cultured in V22 medium and

• Pseudomonas aeruginosa. A series of chemoecological studies of P. aeruginosa has uncovered multifunctional roles of this quinolone class as antibacterial, antifungal, iron-chelating, and autoinducer agents to assist the survival of the producing organisms [32]. Additionally, drug discovery attempts have

A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols

• Anna Czarnecka,
• Emilia Kowalska,
• Agnieszka Bodzioch,
• Joanna Skalik,
• Marek Koprowski,
• Krzysztof Owsianik and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105

• cyclic compounds possessing a diarylmethyl motif, like podophyllotoxin (V) and lasofoxifene (VI), have been a subject of interest as bioactive molecules (Figure 1) [1]. The diarylmethane derivatives, isolated from natural sources, showed antibacterial [2], antiestrogenic and antitumorigenic (I) [3][4][5

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• and in a number of other natural compounds that have shown a highly diverse range of biological activity [1][2][3][4][5][6][7][8][9], like the inhibitory activity of inositol monophosphatase [10][11], antitumor [12], antibiotic [12][13], and antibacterial activity [14] and lipoxygenase inhibitor

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

• significant antibacterial activity against Gram-positive bacterial strains [50]. Several other distamycin analogs were synthesized by replacing one or more pyrrole rings with other heterocycles such as pyrazoles [51], benzofurans [52], thiazoles, thiophenes, imidazole and oxazoles [53] in order to establish a

• . Thus, the conjugate 11 was chosen for further development as an anti-lung cancer therapeutic. In the similar fashion, the same group investigated the correlation between DNA binding and antibacterial activity shown by these novel distamycin alkene-containing analogs (MGB-BP-3, 12 and 13, Figure 4

• , dihydrofuranocoumarins are another class of coumarins possessing anticancer activities. Recently, Ahmadi et al. identified several dihydrofuranocoumarins, especially grandivittin (GRA), from Ferulago macrocarpa (Fenzl) Boiss., and their mechanism of minor groove DNA binding and antibacterial, cytotoxic and antioxidant

An efficient and facile access to highly functionalized pyrrole derivatives

• Meng Gao,
• Wenting Zhao,
• Hongyi Zhao,
• Ziyun Lin,
• Dongfeng Zhang and
• Haihong Huang

Beilstein J. Org. Chem. 2018, 14, 884–890, doi:10.3762/bjoc.14.75

• considerable efforts have been expended to build stereogenic centers of pyrrolidine derivatives using chiral catalysts [7]. As our aim was to construct a small library of polysubstituted pyrroles for antibacterial screening, it prompted us to develop a concise and efficient synthesis of pyrrolo[3,4-c]pyrrole

• could meet our requirement to basically construct a small library of highly functionalized pyrrole derivatives for antibacterial screening or for further chemical manipulations to get more promising compounds. Conclusion In summary, we have developed an efficient, operationally simple protocol to afford

Synthesis of fluoro-functionalized diaryl-λ³-iodonium salts and their cytotoxicity against human lymphoma U937 cells

• Prajwalita Das,
• Etsuko Tokunaga,
• Hidehiko Akiyama,
• Hiroki Doi,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24

• ylides, and (diacyloxyiodo)arenes were also examined for their antibacterial activities against ice nucleation active Pseudomonas syringae, and aryliodonium salts, especially those with electron-withdrawing groups, exhibit higher antibacterial activities [49]. Despite the long history of diaryliodonium

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• pharmacological activities such as: anticancer [1][2], anti-inflammatory [3][4], antioxidant [5], antibacterial [6][7][8], analgesic [9], antiviral [10][11], antimicrobial [12][13], antifungal [6], antiglycemic [14], antiamoebic [15] and antidepressive [16][17]. Considering the immense biological properties

• 200 from the cyclocondensation of 5-amino-1-(2,4-dinitrophenyl)-1H-pyrazole-4-carboxamide (199) with aromatic aldehydes in the presence of iodine in acetonitrile (Scheme 55). The synthesized pyrazolo[3,4-d]pyrimidines were evaluated for antibacterial activities. Venkatesan et al. [132] also used 4

• Pyrazolo[3,4-b]pyrazines have received great attention because of their interesting biological activities such as inhibition of protein kinases [137], blood platelet aggregation [138], bone metabolism improvers [139] as well as antifungal [140], antibacterial [141], antiparasitic [142] and antiviral [143

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

• -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

• -5,6-dihydro-2H-pyran-2-one (9) and 6-nonyl-2H-pyran-2-one (17). Volatiles from Daldinia clavata MUCL 47436. 13C NMR data (chemical shifts in ppm) for 11a–d (125 MHz, C6D6). In vitro antibacterial, antifungal and cytotoxic activity of compounds 9, 14 and 17 in comparison with positive controls