Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• wavenumber values for the lactone C=O stretch was also observed for bands assigned to the C=C bonds as consequence of their conjugation. Evaluation of the growth inhibition and hemolytic activity of S. aureus for the solonamide analogues Initially, the antibacterial activity of all analogues 9 was tested by

• range of 300–0.3 µM. None of the compounds presented antibacterial activity against S. aureus, since no MIC value could be obtained in the range of concentrations tested (MIC > 300 µM). Subsequently, a screening assay was carried out to evaluate the effect of these compounds on the hemolysis of

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• presence of acetic anhydride produced a crude acetamido ester (R)-132 which was transformed into the final N-benzyl amide (R)-130 with of 99.9% ee after crystallization. ʟ-(+)-Furanomycin (Scheme 35) is a natural nonproteinogenic amino acid which showed pronounced antibacterial activity. From several

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• ., anti-inflammatory, anticancer, antibacterial, anxioselective and antiprotozoal [3][4][5]. Furthermore, a number of drugs embracing the imidazopyridine (IP) skeleton have been commercially marketed with their trade names as minodronic acid (for the treatment of osteoporosis), olprinone (for acute heart

Synthesis of 9-O-arylated berberines via copper-catalyzed C_Ar–O coupling reactions

• Qiaoqiao Teng,
• Xinhui Zhu,
• Qianqian Guo,
• Weihua Jiang,
• Jiang Liu and
• Qi Meng

Beilstein J. Org. Chem. 2019, 15, 1575–1580, doi:10.3762/bjoc.15.161

• natural alkaloid extracted from ranunculaceae, rutaceae and berberidaceae, which features a tetracyclic isoquinoline core unit. It was widely used as antibacterial agent [1] and has shown myriad therapeutic potencies in tumor cell suppression [2][3] and various chronic disease management [4]. In most

Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

• Aleksandr S. Krylov,
• Artem A. Petrosian,
• Julia L. Piterskaya,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159

• number of drugs and [1,2,4]triazolo[4,3-a]pyridines were shown to have herbicidal [5][6], antifungal [7], neuroprotective [8][9] and antibacterial activity [10]. In addition, [1,2,4]triazolopyridine has been used as electron-acceptor unit in the synthesis of organic light emitting diodes (OLED) [11]. 2

Molecular basis for the plasticity of aromatic prenyltransferases in hapalindole biosynthesis

• Takayoshi Awakawa and
• Ikuro Abe

Beilstein J. Org. Chem. 2019, 15, 1545–1551, doi:10.3762/bjoc.15.157

• beneficial bioactivities, exemplified by 12-epi-hapalindole E isonitrile, which exhibits antibacterial, antifungal, and antimycobacterial activities [16], and ambiguine I, which induces apoptosis and cell-cycle arrest through the inhibition of an NF-κB-related regulation pathway [17]. To investigate their

Synthesis of pyrrolo[1,2-a]quinolines by formal 1,3-dipolar cycloaddition reactions of quinolinium salts

• Anthony Choi,
• Rebecca M. Morley and
• Iain Coldham

Beilstein J. Org. Chem. 2019, 15, 1480–1484, doi:10.3762/bjoc.15.149

• with a quinoline. Pyrroloquinolines have been found to show antibacterial and antifungal activity, to be ligands for the NK1 receptor, and to be effective against the Hif hypoxia pathway in cancer cell lines [36][37][38]. Almost all of the examples of dipolar cycloaddition reactions involving

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• , Gothenburg, Sweden 10.3762/bjoc.15.147 Abstract The synthesis and antibacterial activity of two new highly truncated derivatives of the natural product abyssomicin C are reported. This work outlines the limits of structural truncation of the natural product and consequently provides insights for further

• physicochemical properties that NPs typically show [3]. Abyssomicin C (AbC) is an NP with antibacterial activity that was isolated from the marine actinomycete strain Verrucosispora AB-18-032 in 2004 [4][5]. It shows antibacterial activity against Gram-positive bacteria, including resistant pathogens such as

• the same time, and these compounds did not show any antibacterial activity (Figure 1). Consequently, the enone moiety of AbC was proposed to play an essential role in the antibiotic activity. Indeed, in a subsequent study it was shown that AbC has a unique mechanism of action amongst NPs: it is a

One-pot activation–alkynylation–cyclization synthesis of 1,5-diacyl-5-hydroxypyrazolines in a consecutive three-component fashion

• Christina Görgen,
• Katharina Boden,
• Guido J. Reiss,
• Walter Frank and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 1360–1370, doi:10.3762/bjoc.15.136

• ingredients [8][9][10][11], as ligands [12][13], and as chromophores [14][15][16], the partially unsaturated 2H-pyrazolines have particularly attracted attention for instance as antibacterial [17], anti-inflammatory [18], antidiabetic [19], and antidepressive [20] agents. Especially, 1-acylpyrazolines have

• ) and antibacterial activity (center and right). ORTEP plot of 5-benzoyl-3-phenyl-1H-pyrazole (6a) (thermal ellipsoids at 30% probability); the direction of intermolecular N−H···O hydrogen bonding is indicated by dashed lines. Ellipsoid plot of 1-Boc-5-benzoyl-5-hydroxypyrazoline 5a. ORTEP plot and

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• available starting materials including scaffold diversity. A small focused compound library of 23 Ugi products was created and screened for antibacterial activity. Keywords: antibacterial activity; Doebner reaction; pyrazolo[3,4-b]pyridine carboxylic acids; Ugi reaction; Introduction Modern medicinal

• adding compounds 12a–f. The purity and structures of the obtained heterocyclic products were established by means of NMR spectroscopy, mass spectrometry, and elemental analysis. The final assignment of the structures 11 and 12 was made by X-ray analysis for the structure 11n (Figure 1). Antibacterial

• experiments. Particularly, the evaluation of the antibacterial activity of the small library of new compounds 11 and 12 was carried out. We next screened some selected compounds for their antibacterial activity (Table 2, Supporting Information File 1) against the reference bacterial strains Bacillus subtilis

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• derivatives show a large variety of biological activities [21][22][23], such as COX-2 inhibition [24], glucokinase activation [25], sodium channel blocking [26], antimycobacterial [27], antiproliferative [28] or carbonic anhydrase inhibition [29], as well as antifungal and antibacterial properties [30

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