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

• pressure can lead to the overgrowth of the initial infective population with a resistant variant of the pathogen, rendering the antibiotic substance ineffective. Especially prevalent in the hospital setting, the abundance of resistance prevents efficient treatment of infected patients. The so-called ESKAPE

• , or the formation of bacterial biofilms, can be inhibited. Numerous reviews have detailed these processes addressing various QS pathways [30][72][73]. The antibiotic azithromycin (22), which does not have significant bactericidal activity for P. aeruginosa, but interferes with its quorum sensing

• pathways, was studied in a clinical trial (Figure 6) [74]. The macrolide antibiotic of natural origin, which does not resemble the structures of signal molecules, was shown to reduce the presence of quorum sensing molecules in vitro and in vivo. It prevented the selection of QS-mutants (lasR) that rapidly

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

• , is an imperative goal to stay ahead of the evolution of antibiotic resistance. Herein we report the synthesis of a 3-decyltetramic acid analogue of the ureido dipeptide natural antibiotic leopolic acid A. The key step in the synthetic strategy is an intramolecular Lacey–Dieckmann cyclization reaction

• 20th century. However, the continued emergence of multidrug-resistant bacteria, mainly due to the abuse of antimicrobial molecules (e.g., for treatment of bacterial skin diseases [1]), emphasises the urgent need for novel antibiotic families. In this regard, natural products are privileged compounds

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• , these analogues may also have antibiotic, antifungal, anticancer, antiparasitic, and immunosuppressive properties. Conclusion This study demonstrated a viable approach to synthesize spinetoram J and its analogues. Compared with the previous semi-synthesis of spinetoram J, the improved semi-synthesis

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

• an antibiotic [94]. In this methodology, N-(p-hydroxyphenyl)cyanoacetamides 65 were cyclized to corresponding 4-spiro-β-lactam-3-carbonitriles 66 in useful yields using PIDA (15) as an electrophile in the presence of KOH as base in anhydrous ethanol at room temperature (Scheme 22). In 2014, Fan and

• starting from catechol derivative 142. Marine sesquiterpenoids are mainly known for their biological importance such as antitumor, antiviral and antibiotic properties [132]. In this report, the catechol-derived starting substrate 142 was cyclized to spirocyclic product 143 in 67% yield using PIFA (31) as

• pathway for the synthesis of the naturally occurring antibiotic platensimycin (154) which is isolated from Streptomyces platensis. In this report, 6-methoxy-1,4-naphthoquinone-4-ethylene ketal (153) was synthesized by intermolecular oxidative cyclization of 7-methoxy-α-naphthol (152) with ethylene glycol

Defining the hydrophobic interactions that drive competence stimulating peptide (CSP)-ComD binding in Streptococcus pneumoniae

• Bimal Koirala,
• Robert A. Hillman,
• Erin K. Tiwold,
• Michael A. Bertucci and
• Yftah Tal-Gan

Beilstein J. Org. Chem. 2018, 14, 1769–1777, doi:10.3762/bjoc.14.151

• (CSP), to acquire antibiotic resistance and establish an infection. In this work, we sought to define the binding pockets within the ComD1 receptor used for binding the hydrophobic side-chain residues in CSP1 through the introduction of highly-conservative point mutations within the peptide

• as the competence regulon, is centered on the competence stimulating peptide (CSP, Figure 1). S. pneumoniae utilizes the regulon to become competent and acquire antibiotic resistance from the environment, initiate its attack on the human host through virulence factor production, and protect itself

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• skunk oil [4], alliin (2), the precursor to 1-propenesulfinic acid which rearranges to the sulfine (Z)-propanethial-S-oxide, the lachrymatory factor of onions, (Allium cepa L), and allicin (3), the thiosulfinate with antibiotic properties from garlic (Allium sativum L.) [5]. On the other molecular

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

•  15) [63]. Similar reaction conditions were applied by Nie et al. in the total synthesis of the nucleoside antibiotic A201A [64]. Notably, the n-Bu3P-ADDP reagent system led here to the formation of the pure α-glycoside. Likewise, a Mitsunobu glycosylation of complex phenols was successfully

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

Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination

• Jiyun Sun,
• Xiaohua Zhen,
• Huaibin Ge,
• Guangtao Zhang,
• Xuechan An and
• Yunfei Du

Beilstein J. Org. Chem. 2018, 14, 1452–1458, doi:10.3762/bjoc.14.123

• potential anti-HIV drug bearing a NCF3 moiety. 2H-Azirines are a class of highly strained and reactive molecules containing a C–N double bond. The exclusive framework can be found in some natural products [43][44][45][46][47], which were shown to possess antibiotic activities [43][44]. Furthermore

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

• antibiotic producers (as of Jan. 20, 2018). As part of our program to further explore this unique pharmacological resource, rhizobacteria of the genus Burkholderia were collected and tested for the production of antimicrobial metabolites against a panel of plant and animal pathogens consisting of 4 bacteria

Acyl-group specificity of AHL synthases involved in quorum-sensing in Roseobacter group bacteria

• Lisa Ziesche,
• Jan Rinkel,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 1309–1316, doi:10.3762/bjoc.14.112

• regulate several physiological traits regulated by cell density, the ‘quorum’ [11][12][13][14][15][16], in roseobacters, e.g., in the production of the antibiotic tropodithietic acid in Phaeobacter inhibens [15] and cell differentiation in Dinoroseobacter shibae [14]. Roseobacter group AHLs are

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

• activity [14][15][16]. Troponoids 3–10 have been reported in the literature in a number of natural forms (Figure 1) [1][2][3][4][5][6][7][8]. These compounds have a structural class spacing from the simple monocyclic tropones, such as the potent antifungal and antibiotic monoterpene β-thujaplicin (4) [17

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

• the past few years. Keywords: alkylators; antibiotic; anticancer; antineoplastic; antiproliferative; DNA recognition; groove binders; hairpin polyamides; Hoechst 33258; intercalators; Review 1. Introduction DNA is one of the central components of cellular machinery and storage unit of genetic

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

• Felix Scheidt,
• Christian Thiehoff,
• Gülay Yilmaz,
• Stephanie Meyer,
• Constantin G. Daniliuc,
• Gerald Kehr and
• Ryan Gilmour

Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88

• siderophore antibiotic D-fluviabactin, the cytotoxic agent westiellamide, the antifungal macrodiolide leupyrrin A1 and the antitumour compound BE-70016 (Figure 1). In addition, synthetic polymers based on the 2-oxazoline building block constitute versatile platforms for a range of biomedical applications

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• resultant compounds are called carbocyclic C-nucleosides. Examples of natural and synthetic C-nucleosides. Pseudouridine and formcycin are among several naturally occurring C-nucleosides that are being studied for their role in RNA biology and antibiotic properties respectively. In the recent past

Continuous multistep synthesis of 2-(azidomethyl)oxazoles

• Thaís A. Rossa,
• Nícolas S. Suveges,
• Marcus M. Sá,
• David Cantillo and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2018, 14, 506–514, doi:10.3762/bjoc.14.36

• antibiotic or antimicrobial properties such as pimprinine [4] or phenoxan [5] (Figure 1a). Also many synthetic active pharmaceutical ingredients (API) contain the oxazole as an active moiety [1][2][3]. Oxaprozin, for example, is an important non-narcotic, non-steroidal anti-inflammatory drug [6][7

• ]. Sulfamoxole is a broad-spectrum antibiotic for the treatment of bacterial infections (Figure 1b) [8]. In addition, ongoing studies show the potential of amino and amido-oxazoles to act as fluorescent dipeptidomimetics (Figure 1c) [9]. Due to their diene character, oxazoles find also use as intermediates in

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

Binding abilities of polyaminocyclodextrins: polarimetric investigations and biological assays

• Marco Russo,
• Daniele La Corte,
• Annalisa Pisciotta,
• Serena Riela,
• Rosa Alduina and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2751–2763, doi:10.3762/bjoc.13.271

• control experiments [58]. It is worth mentioning here that bacteria have different ways to interact with extracellular DNA. In some cases they can naturally internalize and integrate exogenous DNA (natural competence) and this can result in the acquisition of new genetic traits (e.g., antibiotic

• maintenance by pathogenic bacteria, such as P. aeruginosa and S. aureus [60][61][62]. In addition, eDNA with its negative charge can sequester cationic antibiotics contributing to antibiotic resistance; thus, removing eDNA from the biofilm matrix can weaken the biofilm and can raise its susceptibility to

• antibiotics. The fact that these cyclodextrin derivatives might be loaded with an antibiotic allows speculating that a possible antibiotic–CD complex could target the pathogen and in the meanwhile to bind and sequester extracellular DNA, inhibiting its role in vivo. Finally, a particular mention is deserved

An efficient synthesis of 1,6-anhydro-N-acetylmuramic acid from N-acetylglucosamine

• Matthew B. Calvert,
• Christoph Mayer and
• Alexander Titz

Beilstein J. Org. Chem. 2017, 13, 2631–2636, doi:10.3762/bjoc.13.261

• in only five steps from the cheap starting material N-acetylglucosamine. This efficient synthesis should enable future studies into the importance of 1,6-anhydromuramic acid in bacterial cell wall recycling processes. Keywords: N-acetylmuramic acid; anhydrosugars; antibiotic resistance; bacterial

Consecutive hydrazino-Ugi-azide reactions: synthesis of acylhydrazines bearing 1,5-disubstituted tetrazoles

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

Beilstein J. Org. Chem. 2017, 13, 2596–2602, doi:10.3762/bjoc.13.256

• linatine [24] and the antibiotic negamycin, active against Gram-negative bacteria [25], among others [26]. Furthermore, trisubstituted acylhydrazines were found to serve as tertiary amide bioisosters [27]. Therefore, it is highly desirable to have a method that allows an easy incorporation of hydrazino

Exploring mechanochemistry to turn organic bio-relevant molecules into metal-organic frameworks: a short review

• Vânia André,
• Sílvia Quaresma,
• João Luís Ferreira da Silva and
• M. Teresa Duarte

Beilstein J. Org. Chem. 2017, 13, 2416–2427, doi:10.3762/bjoc.13.239

• using 4-aminosalicylic acid and piracetam. 4-Aminosalicylic acid is an antibiotic that has been used in the treatment of tuberculosis, inflammatory bowel diseases, namely distal ulcerative colitis [125][126] and Crohn’s disease [127], while piracetam is a nootropic drug used to improve cognitive

Sulfation and amidinohydrolysis in the biosynthesis of giant linear polyenes

• Hui Hong,
• Markiyan Samborskyy,
• Katsiaryna Usachova,
• Katharina Schnatz and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2017, 13, 2408–2415, doi:10.3762/bjoc.13.238

• in a genome-led approach to the uncovering of novel enzymology in the biosynthetic pathways to antibiotic natural products [23][24][25][26]. Here, we have used in-house whole-genome sequencing to characterise the closely-related gene clusters to the sulfated antifungal linear polyenes clethramycin

• . Sulfonation has been suggested as a novel approach to block the development of antibiotic resistance [33][34] while the discovery of the sulfated metabolite FR901379 was a critical breakthrough in the successful clinical development of micafungin to combat systemic fungal infections [12]. HPLC–UV–MS analysis

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• . Gilchrist [70] employed oximinoalkylation of pyrrole as the initial stage in the synthesis of 1,2-dihydropyrrolizinone antibiotic 82 [71][72][73] (Scheme 29). The addition of ethyl 2-nitrosoacrylate (generated from ethyl bromopyruvate oxime) to pyrrole under basic conditions afforded product 67a in 61

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

• chain is of key importance for the antibiotic activity of the fusaricidins and their selective inhibition of bacterial cells due to the interaction with phospholipid cell membranes [1]. Genetic analysis of the producing organisms suggests that the biosynthesis of this essential part of the fusaricidins