α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• -lactams are important lead compounds, e.g., derivatives with antibacterial activity were discovered, what gains importance with respect to the increasing bacterial resistance toward traditional β-lactam antibiotics [35][36][37][38][39]. Various synthetic pathways can be applied for the construction of the

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• antibiotics [14], antimicrobials [15], antimalarials [16], antitumor agents [17], and medicinal agents [18]. Thus, much attention has been paid to the synthesis of phosphonodepsipeptides. To date, diverse synthetic strategies of phosphonodepsipeptides 1 have been developed. The strategies comprise the

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• , generated in the first instance so that the producing organism is protected from its deleterious effects, and can be activated outside the cell by glucosidases. Fluorinated natural products via precursor-directed biosynthesis The modification of known antibiotics and other natural products is an important

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• stereoselective methods for the synthesis and transformations of cyclopropane derivatives. These investigations gained a significant interest, because cyclopropane and cyclopropene fragments are present in the structures of many biologically active substances, such as antibiotics, anticancer, and antimycotic

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• in several worldwide-consumed drugs and agrochemicals [32][33][34][35][36][37][38]. Figure 1 shows examples of these pharmacologically active compounds, such as the antibiotics retapamulin and cefmetazole [32][33][34][35], the anticancer agent RETRA [36], and agrochemicals with pesticidal (malathion

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• Bidyut Kumar Senapati Department of Chemistry, Prabhat Kumar College, Contai, 721404, India, Tel.: +91 8145207480 10.3762/bjoc.17.7 Abstract The inthomycin family of antibiotics, isolated from Streptomyces strains, are interesting molecules for synthesis due to their characteristic common oxazole

• application of various efforts towards the synthesis of inthomycins and their analogues systematically. Keywords: antibiotics; inthomycins; oxazololomycin; Stille coupling; total synthesis; Introduction Inthomycins, alternatively known as phthoxazolins, are a class of compounds in which a methylene

• have generated immense interest among the chemists. Over the past two decades, a wide variety of synthetic strategies have been dedicated towards the synthesis of the inthomycin class of antibiotics. An earlier report on the total synthesis of oxazolomycins provides an overview of the author’s

Secondary metabolites of Bacillus subtilis impact the assembly of soil-derived semisynthetic bacterial communities

• Heiko T. Kiesewalter,
• Carlos N. Lozano-Andrade,
• Mikael L. Strube and
• Ákos T. Kovács

Beilstein J. Org. Chem. 2020, 16, 2983–2998, doi:10.3762/bjoc.16.248

• of supplemented pure NRP compounds, e.g., surfactin and bacillaene. The impact of antibiotics on algae-associated bacterial communities was investigated by Geng et al. in 2016, who revealed a dose-depended influence of pure tropodithietic acid on the microbiome structure of Nannochloropsis salina [63

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• , antibiotics and in many types of synthetic drugs [1][2][3][4][5][6][7][8][9][10][11][12]. N-Sulfonyl amidines have received considerable attention because they exhibit various types of pharmaceutical properties and biological activities [13][14][15][16][17][18][19][20][21] and also have been used as

Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of ¹J_C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

• Md. Rokon Ul Karim,
• Enjuro Harunari,
• Amit Raj Sharma,
• Naoya Oku,
• Kazuaki Akasaka,
• Daisuke Urabe,
• Mada Triandala Sibero and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 2719–2727, doi:10.3762/bjoc.16.222

• habitat [6][7]. Their secondary metabolite machinery is activated in the sea, as indicated by the isolation of enediyne antitumor antibiotics from marine invertebrates. Namenamicin [8] and the shishijimicins [9], the chalicheamicin-type enediyne polyketides, were isolated from a colonial tunicate. These

Muyocopronones A and B: azaphilones from the endophytic fungus Muyocopron laterale

• Ken-ichi Nakashima,
• Junko Tomida,
• Tomoe Tsuboi,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 2100–2107, doi:10.3762/bjoc.16.177

• the antibiotics were serially diluted (over a concentration range of 1–1024 μg/mL) into the wells of a 96-well plate. Following addition of the bacterial inoculum, the microtiter plate was incubated at 37 °C for 18 h. The microorganisms were cultured in CAMHB (cation-adjusted Mueller-Hinton broth

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

• Esra Demir,
• Ozlem Sari,
• Yasin Çetinkaya,
• Ufuk Atmaca,
• Safiye Sağ Erdem and
• Murat Çelik

Beilstein J. Org. Chem. 2020, 16, 1805–1819, doi:10.3762/bjoc.16.148

• considerable use as antibiotics [1], immunomodulators [2], antibacterials [3], as well as synthetic intermediates and chiral auxiliaries for various organic conversions [4][5][6][7]. Linezolid [1][2][3] (3) and cytoxazone [8][9] (4) are oxazolidinone derivatives having significant biological activities

Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens

• Sharavathi G. Parameswarappa,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2020, 16, 1693–1699, doi:10.3762/bjoc.16.140

• developing countries [3]. With increasing antimicrobial resistance to antibiotics, vaccines are becoming even more important to control these pathogens. Despite the availability of multivalent polysaccharide and glycoconjugate vaccines such as Pneumovax, Prevnar® 13, and Synflorix, pneumonococcal diseases

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• effects [32], inhibits both hERG current and the expression of hERG protein [33], inhibits the pancreatic lipase [34], shows antiradical, revitalizing and antifibrotic properties for dermatological applications [35], manifests a synergic effect with antibiotics [36], and displays antitumoral activities

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• . Though not alkylated, the close structural similarity to 3 suggests that 1 is also a member of the 2-alkyl-4-quinolone class signaling molecules/antibiotics known from Pseudomonas aeruginosa and some Burkholderia species [26][27]. Quinolones of this class are classified into two lineages, those with or

Anthelmintic drug discovery: target identification, screening methods and the role of open science

• Frederick A. Partridge,
• Ruth Forman,
• Carole J. R. Bataille,
• Graham M. Wynne,
• Marina Nick,
• Angela J. Russell,
• Kathryn J. Else and
• David B. Sattelle

Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105

• -Wolbachia treatments. These treatments target the bacterial symbiont Wolbachia which is essential for development, growth and survival of many filarial parasites. Targeting of Wolbachia with antibiotics has been shown to have curative efficacy against lymphatic filariasis [53] and importantly is safe to

• administer in L. loa co-endemic regions [54]. However, currently available effective antibiotics are unsuitable for public health MDA strategies due to contraindications and treatment duration and therefore novel compounds are required. Current anthelmintics – onchocerciasis Onchocerciasis (river blindness

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• appendage in compound 2 is unprecedented in natural products, only to see its (Z)-isomer in a siderophore of Mycobacterium avium [32]; the side chain on the spiroacetal rings in compounds 2–4 lack hydroxylation at C-31, which is the common modification shared with all oligomycin class antibiotics

• structure 1b were similarly simulated by using 44 structures as the OPLS3e-minimized structures and 7 conformers as the DFT-optimized structures. Antimicrobial assay The antimicrobial assay was carried out in the same manner as reported previously [49]. MICs of reference antibiotics, kanamycin and

Fabclavine diversity in Xenorhabdus bacteria

• Sebastian L. Wenski,
• Harun Cimen,
• Natalie Berghaus,
• Sebastian W. Fuchs,
• Selcuk Hazir and
• Helge B. Bode

Beilstein J. Org. Chem. 2020, 16, 956–965, doi:10.3762/bjoc.16.84

• global threat of multiresistant pathogens has to be answered by the development of novel antibiotics. Established antibiotic applications are often based on so-called secondary or specialized metabolites (SMs), identified in large screening approaches. To continue this successful strategy, new sources

• of fabclavines as major antibiotics in several entomopathogenic strains, our work lays the foundation for the rapid fabclavine identification and dereplication as the basis for future work of this widespread and bioactive SM class. Keywords: antibiotic; fabclavine; NRPS-PKS hybrid; secondary

• metabolite; Xenorhabdus; Introduction The constantly increasing threat of multiresistant pathogens requires the development of new antibiotics, as they are indispensable to maintain the state of health of our society [1]. Bacterial natural products, also called secondary or specialized metabolites (SM

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• example, in anti-HIV therapy, MUC1-based antitumor vaccines, or as antibiotics [12][13][14]. Especially glycans bearing noncanonical amino acids, which can only be introduced into a peptide by organic synthesis, are suitable for cancer therapy since they show better resistance to enzymatic degradation in

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• applications as antibiotics [1], antiproliferative agents [2], anti-inflammatories [3] and antithrombotics [4]. They are also found in many bioactive natural products [5][6][7][8], some of which display anti-HIV-1 [9] and antimitotic activities [10], among others. Thiazolines also find use in organic synthesis

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• mechanisms of pathogenic Gram-negative bacteria against antibiotics, such as polymyxin B and colistin [3]. The main effect of Ara4N incorporation into the lipid A part – and, less frequently, into the inner core region of LPS [4] – is thought to originate from blocking the electrostatic interaction of

Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica

• Soleiman E. Helaly,
• Wilawan Kuephadungphan,
• Patima Phainuphong,
• Mahmoud A. A. Ibrahim,
• Kanoksri Tasanathai,
• Suchada Mongkolsamrit,
• Janet Jennifer Luangsa-ard,
• Souwalak Phongpaichit,
• Vatcharin Rukachaisirikul and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2968–2981, doi:10.3762/bjoc.15.293

• , in particular orthopedic implant-related infections, since implants coated with proteins facilitate bacterial attachment and biofilm development [1]. In general, bacteria are known to employ different strategies to cope with the presence of antibiotics, of which a biofilm, an aggregate of

• microorganisms held together within a self-produced matrix of extracellular polymeric substances, plays an important role as a main virulence determinant in staph infections [1][2]. Within a biofilm, bacteria become tolerant toward antibiotics and host immune responses greater than their planktonic (free

• leave target microbes vulnerable to antibiotics [6]. A complementary approach of using a combination of an antibiotic with a biofilm inhibitor appears to be a promising solution to control biofilm-associated pathogens, as based on the evidence that traditional antibiotics were more effective when used

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• ; mutasynthesis; NRPS; peptide synthesis; Introduction Resistance to antibiotics is currently a major threat to public health. Especially Gram-negative bacterial pathogens are of concern, due to their widespread development of resistance mechanisms. To address this general antimicrobial resistance problem, new

• variants of known antibiotics are being developed and were approved in the last few years, also comprising drugs active against Pseudomonas aeruginosa, one of the currently most problematic bacterial pathogens [1]. Especially among the quinolones, cephalosporins and carbapenems new compounds have been

• identified. In addition, the development of new β-lactamase inhibitors is ongoing and may restore the activity of known β-lactams against β-lactamase-producing strains [2]. Unfortunately, most of these antibiotics rely on known modes of action and do not target novel binding sites. To circumvent established

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

• . Cyclic thioether peptides have been found in the chemical skeletons of natural products and synthetic ones that display a wide variety of activities, including antibiotics [31], vascular cell adhesion molecule-1 antagonists [32] and anticardiolipin antibodies [33][34]. Two MBH adducts (2) (R = Me, heptyl

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• ] variations will further enhance the production rate [25]. Alternatively, permanent integration of the heterologous genes into the host genome is an alternative strategy to circumvent metabolic stress by antibiotics, which are required to maintain a plasmid in the production host [28]. Nevertheless, genomic