Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

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

• bringing new molecules through to clinical practice. At an earlier stage of development, the anti-Wolbachia (A·WOL) consortium, a partnership including the Liverpool School of Tropical Medicine and AbbVie discovered ABBV-4083 (12), an antibiotic effective in preclinical models as a macrofilaricide by

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

• class, and the corresponding study revealed that fabclavines alone are the major bioactive compound class in X. szentirmaii [15]. In combination with our bioactivity data of fabclavine-producing mutants, it is obvious that this class of compounds is the major driver for the overall antibiotic activity

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• ) as the final product. Kempene diterpenes The first enantioselective synthesis of kempene diterpenes 14a–c, natural compounds exhibiting a significant antibiotic activity against B. subtilis, relying on the domino enyne metathesis of the adequate dienyne precursors as a key step, was disclosed by Metz

Towards the total synthesis of chondrochloren A: synthesis of the (Z)-enamide fragment

• Jan Geldsetzer and
• Markus Kalesse

Beilstein J. Org. Chem. 2020, 16, 670–673, doi:10.3762/bjoc.16.64

• (Cmc5) by the groups of Höfle and Reichenbach in 2003 [12]. This PKS/NRPS-derived natural product shows only weak antibiotic effects in agar diffusion tests against Micrococcus luteus, Schizosaccharomyces pombe, Bacillus subtilis and Staphylococcus aureus [12]. The relative and absolute stereochemistry

Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction

• Yong Li,
• Zheng Huang,
• Jia Xu,
• Yong Ding,
• Dian-Yong Tang,
• Jie Lei,
• Hong-yu Li,
• Zhong-Zhu Chen and
• Zhi-Gang Xu

Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63

• exhibit a wide range of biological activities, including antibiotic [8], antiviral [9], antifungal [10], phytotoxic [11], cytotoxic [12][13], and enzyme inhibitory activities against bacterial DNA-directed RNA polymerase [14]. The wide range of biological activity and structural variation of this class of

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

• Panagiotis S. Gritzapis,
• Panayiotis C. Varras,
• Nikolaos-Panagiotis Andreou,
• Katerina R. Katsani,
• Konstantinos Dafnopoulos,
• George Psomas,
• Zisis V. Peitsinis,
• Alexandros E. Koumbis and
• Konstantina C. Fylaktakidou

Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33

• action via its combination with the photosensitizer. It is worth mentioning that, mainly in dermatology, even UVB irradiation is considered of therapeutic use [16][17][18]. Besides the anticancer activities of photosensitizers [19][20][21], “post-antibiotic era” is experimenting with photosensitizers as

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• applied, photopharmacology has drawn great interest for studies of crucial biological processes in a range of fields, from neuroscience [5][6] and G-protein-coupled receptor (GPCR) function [7][8] to antibiotic research [9]. Particularly in the context of MT biology, photopharmacology is an attractive

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• targets [2][7][8]. As a result, the market for peptide drugs (e.g., hormones, receptor antagonists, anticancer, or antibiotic agents) grows faster than that of many other chemotherapeutics [9]. Significant general disadvantages of peptides as pharmacological agents are their poor oral bioavailability, low

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

• derivatives. These intermediates will be of value for their future conversion into transition state analogues as well as for the introduction of various lipid extensions at the anomeric phosphonate moiety. Keywords: antibiotic resistance; glycosyl phosphonate; glycosyl transferase; lipid A

• the looming antibiotic crisis [5]. 4-Amino-4-deoxy-ʟ-arabinose units are activated as the phosphodiester-linked undecaprenyl derivative [6], which is then transferred by the action of several Ara4N transferases (ArnT, Figure 1) [7]. The synthesis of potential inhibitors of the biosynthesis of Ara4N

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

• -floating) cells, leading to an occurrence of reinfection once the antibiotic therapy is terminated [3][4][5]. In recent years, efforts to find new molecules that can selectively inhibit biofilms have steadily increased, based on the hypothesis that new agents can effectively disrupt biofilm formation and

• 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

• Saarbrücken, Germany 10.3762/bjoc.15.286 Abstract The argyrins are secondary metabolites from myxobacteria with antibiotic activity against Pseudomonas aeruginosa. Studying their structure–activity relationship is hampered by the complexity of the chemical total synthesis. Mutasynthesis is a promising

• sarcosine (Sar) and derivatives. Chemical synthesis of the native sequence ᴅ-Ala-Dha-Sar thioester required revision of the sequential peptide synthesis into a convergent strategy where the thioester with sarcosine was formed before coupling to the Dha-containing dipeptide. Keywords: antibiotic; argyrin

• resistances in clinically used bacterial targets, innovative antiinfective strategies comprising new antibiotic classes and virulence-attenuating compounds have been developed [3][4]. The argyrins 1–8 are a family of 8 naturally occurring cyclic peptides isolated by Sasse, Höfle and co-workers from the

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

• determining the minimum inhibitory concentration against two antibiotic-susceptible reference strains of S. aureus, S. aureus ATCC 25923 and S. aureus ATCC 29213 (see Supporting Information File 1, assay 1) [41]. Two-fold serial dilutions were performed, allowing to test several concentrations within the

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

• , antibiotic, neuroprotective and even insecticidal activities, which makes these compounds high-value commercial targets for the chemical and pharmaceutical industry [9][10]. Structural diversity of diterpenes is created by the terpene synthase (TPS) enzyme family, which use acyclic isoprenoid precursors to

• -dolabellatriene (12) possesses a mainly weak antibiotic activity against different types of Staphylococcus aureus strains (two epidemic MRSA strains, a macrolide-resistant variant and two multidrug-resistant efluxing strains) [72]. By contrast, 3,7,18-dolabellatriene (12, Scheme 3), only altered at C14 with a

• substances, in addition to being key flavor ingredients [78], play a major role in the defence against insects, pathogenic microbes and herbivores [79]. Furthermore, β-CBT 17 showed additional antibiotic activity against multidrug resistant S. aureus strains, [80], as well as neuroprotective activity [81

Isolation of fungi using the diffusion chamber device FIND technology

• Benjamin Libor,
• Henrik Harms,
• Stefan Kehraus,
• Ekaterina Egereva,
• Max Crüsemann and
• Gabriele M. König

Beilstein J. Org. Chem. 2019, 15, 2191–2203, doi:10.3762/bjoc.15.216

• -stimulating, and anticancer activities [2]. Since the World Health Organization (WHO) declared antibiotic resistance a global threat and urged the search for new antibiotics, the interest in fungal metabolites increased recently. In order to find new structural types, novel source organisms have to be

• laboratory [4]. E. terrae produced a novel antibiotic called teixobactin with no detectable resistance, as it interacts with key functions of cell wall synthesis that do not undergo fast evolutionary changes [5]. Inspired by this approach we developed the Fungal one-step IsolatioN Device (FIND), in order to

• axenic. From experiment 1, 39 isolates were microscopically identified as belonging to genera common in soil, e.g., Fusarium, Penicillium or Trichoderma and thus were not further processed. The addition of antibiotics prevented bacterial contamination in all marine samples. However, a few antibiotic

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

• Sara Peeters,
• Linn Neerbye Berntsen,
• Pål Rongved and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2019, 15, 2156–2160, doi:10.3762/bjoc.15.212

• efficient way of synthesizing two synthetically versatile 4-quinolone-3-carboxylate building blocks by cyclopropanation-ring expansion of 3-chloroindoles with α-halodiazoacetates as the key step. This novel transformation was applied towards the synthesis of the antibiotic drug norfloxacin. Keywords

• compounds with biological activities ranging from antitumor, antiviral, antibiotic and antiparasitic to cannabinoid receptor modulating [22][23][24][25][26][27][28]. Despite the attractive features of the quinolone-3-carboxylate scaffold, there are only four reported routes towards this valuable structural

• ]. Norfloxacin (1) is considered to be the first broad band antibiotic and its structurally related cousin ciprofloxacin (2) is one of the most prescribed antibiotics even after 20 years of clinical use. We elected 1 as a synthetic target for our novel approach towards FQs (Scheme 4). Chlorination of

Genome mining in Trichoderma viride J1-030: discovery and identification of novel sesquiterpene synthase and its products

• Xiang Sun,
• You-Sheng Cai,
• Yujie Yuan,
• Guangkai Bian,
• Ziling Ye,
• Zixin Deng and
• Tiangang Liu

Beilstein J. Org. Chem. 2019, 15, 2052–2058, doi:10.3762/bjoc.15.202

• structurally diverse (poly)cyclic core skeletons [3][12]. A set of post-modification enzymes can transform core sesquiterpene skeletons into different kinds of sesquiterpenoids with potential anticancer, cytotoxic and antibiotic functions [13]. More than 121 skeleton structures derived from the sesquiterpene

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

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

• Leticia Monjas Peter Fodran Johanna Kollback Carlo Cassani Thomas Olsson Maja Genheden D. G. Joakim Larsson Carl-Johan Wallentin Department of Chemistry and Molecular Biology, University of Gothenburg, Kemigården 4, 412 96, Gothenburg, Sweden Centre for Antibiotic Resistance Research (CARe

• : abyssomicin C; antibiotic; antibiotic resistance; MRSA; truncated natural products; Introduction Antibiotic resistance is a major threat to global health, and numerous actions are presently taken in both academia and industry to combat this major societal challenge. There are many different approaches to

• 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

Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• ]. In this study, we analyzed the β-proteobacterium Massilia sp. NR 4-1, which had been isolated from a soil sample collected under a nutmeg tree [6]. Although, this strain had already been identified as producer of the antibiotic violacein [6], still not much is known about its secondary metabolism or

Phylogenomic analyses and distribution of terpene synthases among Streptomyces

• Lara Martín-Sánchez,
• Kumar Saurabh Singh,
• Mariana Avalos,
• Gilles P. van Wezel,
• Jeroen S. Dickschat and
• Paolina Garbeva

Beilstein J. Org. Chem. 2019, 15, 1181–1193, doi:10.3762/bjoc.15.115

• crystal structure of 2-MIB synthase. The function of this domain is unknown, but it is conserved in most 2-MIB synthases and not present in any other terpene synthase [20][28]. epi-Isozizaene (3) is a tricyclic sesquiterpene precursor of the antibiotic albaflavenone (17) (Scheme 3) [29]. Furthermore, both

• crystal structure was also the first reported for a bacterial terpene synthase [47]. Pentalenene synthase catalyses the cyclisation of FPP into pentalenene, which is the first step in the biosynthesis of the antibiotic pentalenolactone. This mechanism has been extensively studied and involves the initial

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

• compounds. Molecules containing the isoindolinone moiety are of pharmaceutical interest as anxiolytic (pazinaclone [15], pagoclone [16], and JM1232 [17]), anticancer (lenalidomide) [18], anti-inflammatory (indoprofen) [19] and antibiotic agents (lactonamycin) [20] (Figure 4). In addition, some isoindolinone

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• with high affinity to lectins and with antibiotic activities [34], lectin recognition by n-alkyl thioglycoside liposomes remains unprecedented [33][34]. Moreover, the calculated distance between the two sugar moieties of compound 8 (up to 13 Å, Figure 6) and the presence of flexible arms make these

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

Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

• Andrejs Šišuļins,
• Jonas Bucevičius,
• Yu-Ting Tseng,
• Irina Novosjolova,
• Kaspars Traskovskis,
• Ērika Bizdēna,
• Huan-Tsung Chang,
• Sigitas Tumkevičius and
• Māris Turks

Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

• -7 cells were cultured in RPMI medium supplemented with fetal bovine serum (10%), antibiotic–antimycotic (1.0%). MCF-10A cells were cultured in α-MEM supplemented with FBS (10%), and antibiotic–antimycotic (1.0%). All cells were cultured in an environment equilibrated with 5% CO2 at 37 °C. The cell