Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku,
• Nobuyasu Matsuura,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 297–304, doi:10.3762/bjoc.16.29

• [18]. Herein, we report the fermentation, isolation, structure determination, and bioactivity of two new keto fatty acids, (6E,8Z)-5-oxo-6,8-tetradecadienoic acid (1) and its (6E,8E)-isomer 2, from a coral-associated actinomycete Micrococcus sp. C5-9. Results and Discussion The producing strain C5-9

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

• molecular photoswitch that has only recently been applied as a photoswitchable pharmacophore for control over bioactivity in cellulo. Uniquely, in contrast to other photoswitches that have been applied to biology, the pseudosymmetric hemithioindigo scaffold has allowed the creation of both dark-active and

• cytoskeleton research. Additionally, as the hemithioindigo scaffold allows photoswitchable bioactivity for substituent patterns inaccessible to the majority of current photopharmaceuticals, wider adoption of the hemithioindigo scaffold may significantly expand the scope of cellular and in vivo targets

• cellulo [18]. We showed for the first time that the pseudosymmetry of hemithioindigos can be used to enable a priori design of HTI-based pharmacophores for a single binding site, with higher bioactivity as either the lit-form E- or the dark-form Z-isomer, just by changing substituent patterns, and

Reversible photoswitching of the DNA-binding properties of styrylquinolizinium derivatives through photochromic [2 + 2] cycloaddition and cycloreversion

• Sarah Kölsch,
• Heiko Ihmels,
• Jochen Mattay,
• Norbert Sewald and
• Brian O. Patrick

Beilstein J. Org. Chem. 2020, 16, 111–124, doi:10.3762/bjoc.16.13

• biological activity on and off due to the reversibility of the photoreaction [15]. Indeed, the application of light to induce and control bioactivity of pharmaceuticals or bio(macro)molecules has been convincingly demonstrated in the emerging field of photopharmacology [16][17][18]. Consequently, several

Terpenes

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 2966–2967, doi:10.3762/bjoc.15.292

• pheromones, but also have a long standing history as fragrances used by humans. The oxidised derivatives may be of high interest because of their bioactivity, with some of the most important drugs used in medical applications being of terpenoid origin. Two of the most fanous examples include the diterpenoid

• elucidation, total synthesis, biosynthetic studies, bioactivity and functionalisation for mode of action studies, and other applications of terpenes, e.g. as fragrances. I thank all colleagues who have participated in this issue for their contributions and the whole Beilstein team for the professional support

α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA

• Shital K. Chattopadhyay,
• Subhankar Ghosh,
• Sarita Sarkar and
• Kakali Bhadra

Beilstein J. Org. Chem. 2019, 15, 2524–2533, doi:10.3762/bjoc.15.245

• useful level of bioactivity, α,ß-didehydro SAHA derivatives remain to be explored, to the best of our knowledge. Herein, we disclose two alternative synthetic routes to SAHA and preliminary biological evaluation of some α,ß-didehydro derivatives of SAHA. Results and Discussion Our synthesis of SAHA and α

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• incorporation of three different diversity-generating sites (Scheme 1A), a feature that has been exploited for the construction of libraries of tetrazole-based compounds with potential bioactivity [9][10][11][12][19]. A powerful approach for obtaining hybrid heterocyclic compounds including the tetrazole ring

Targeted photoswitchable imaging of intracellular glutathione by a photochromic glycosheet sensor

• Xianzhi Chai,
• Hai-Hao Han,
• Yi Zang,
• Jia Li,
• Xiao-Peng He,
• Junji Zhang and
• He Tian

Beilstein J. Org. Chem. 2019, 15, 2380–2389, doi:10.3762/bjoc.15.230

• as biosensing/imaging, bioactivity modulation, drug delivery, etc [23][24]. In our system, the Glyco-DTE@MnO2 hybrid sensor undergoes decomposition when encountering the overexpressed intracellular GSH in HepG2 cell lines, following the recovery of the photoswitchable fluorescence signal regulated by

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

• available via the CotB2 mutants is the necessity of further decoration with functional groups, like hydroxylations or epoxidations, to induce the desired bioactivity (Scheme 3). Modification descriptions in the next chapters are composed according to the atom numbering in (Scheme 3). Lead structure for the

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• ) exhibited no significant bioactivity, acremines A–D showed inhibition of P. viticola sporangia germination. In 2015, Wei and co-workers discovered bisacremines E–G, the most complex members of the acremine family, from the soil-derived strain A. persicinum SC0105 [4]. These natural products are presumed to

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

• obtained by four FIND experiments and identified by sequence comparison with the best BLASTn match within the NCBI GenBank database. Supporting Information Supporting Information File 184: Genomic sequences of isolated fungi, data on bioactivity and halotolerance, spectroscopic data of compounds 1 and 2

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• bioactivity, allows the probing of pharmacologically relevant systems with spatiotemporal resolution. A hetero-stilbene lead resulting from the screening of a compound that was originally designed as kinase inhibitor served as a starting point for the design of photoswitchable sirtuin inhibitors. Because the

Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L.

• Annika Stein,
• Dave Compera,
• Bianka Karge,
• Mark Brönstrup and
• Jakob Franke

Beilstein J. Org. Chem. 2019, 15, 2003–2012, doi:10.3762/bjoc.15.196

• importance of the lactone side chain for bioactivity. Conclusion We have discovered and characterised irinans A and B, two new withanolides from P. peruviana with truncated backbones. They resemble mammalian sex hormones of the androstane class. The relative stereochemistry was elucidated based on NOESY

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• investigation of two title animals led to the isolation of four new halogenated laurane-type sesquiterpenoids 1–4, one new aromadendrane-type sesquiterpenoid 6) together with three related known compounds 5, 7 and 8 (Figure 1). Herein, the isolation, structure elucidation and bioactivity evaluation of these

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• no cis product formed. After further removal of the para-methoxyphenyl (PMP) group using ammonium cerium nitrate (CAN), the cyclic β-amino acid ester 5b was obtained with a yield of 80%. Cyclic β-amino acids and derivatives have good bioactivity and are widely used as key synthetic intermediates in

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

• nevaltophines act as prophenoloxidase activators, it is suggested that they have a specific role in the bacteria/nematode/insect symbiosis. Little or nothing is known about the mode of action of this simple amide against S. aureus. Structure–bioactivity studies revealed that the α-keto moiety and the amide

• moiety itself are required for bioactivity [16]. These findings suggest a specific interaction of this electrophilic moiety with a nucleophile. Such an interaction was previously reported for the macrocyclic peptide cyclotheonamide A, isolated from marine sponge Theonella sp. Cyclotheonamide A is

• -methylvaleric moiety (1–7) were active against S. aureus. Substitution of the side chain in the α-keto amide significantly affects the bioactivity, as seen for compounds 8, 9 and 10. Furthermore, attempts to identify a possible target by the incorporation of an α,β-unsaturated carbonyl moiety, as it should bind

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

• 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

• carboxamide group, may contribute to enhance the bioactivity. This fact could be explained by the coplanarity induced by the C-4 carbonyl hydrogen bond interactions with biological targets [3] or complexation with physiological metal cations such as magnesium and zinc [23]. Besides the derivatives 3a and 3b

• , accomplished through temperatures above 200 °C, any derivatization afterwards should maintain the N–H carboxamide group intact, in order to provide the hydrogen bond donor group attached to C-3, which is usually related to the bioactivity of such compounds (Figure 2) [3][23]. In order to obtain an N1-alkylated

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• ]. Conclusion In this study we describe the synthesis of selectively methylated AQs and the influence of methylation on the bioactivity. While the methylation of HHQ is straightforward, selective preparation of methylated HQNO and PQS derivatives required optimized reaction conditions and multistep syntheses

N-Acylated amino acid methyl esters from marine Roseobacter group bacteria

• Hilke Bruns,
• Lisa Ziesche,
• Nargis Khakin Taniwal,
• Laura Wolter,
• Thorsten Brinkhoff,
• Jennifer Herrmann,
• Rolf Müller and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 2964–2973, doi:10.3762/bjoc.14.276

• medium polar core structure [8][16]. Nevertheless, the ecological function of NAMEs and its derivatives could also be antagonistic activity against concurrent biofilm microorganisms, suggested by the bioactivity of some of the compounds as observed in this study and the antimicrobial and antialgal

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

• side-chain residues compared to truncated side-chains or those that introduce electrostatic effects. Finally, our results further correlated helicity with bioactivity. Combined, the results of this study can be used to design novel CSP-based QS modulators with improved pharmacological properties that

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• , hydrophobicity, and amphipathicity, which are known to be important for interacting with membranes, exerting bioactivity against microorganisms and cancer cells, and suppressing unwanted hemolytic activity [10]. Since the aforementioned peptides were designed to target negatively charged bacterial membranes, we

• the importance of certain physicochemical properties for the bioactivity of these two peptides, in line with previous work by Torres et al. [9]. Currently, there is no consensus on how the biophysical properties of peptides influence their antimicrobial and antitumoral activities. However, in the

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

• characterization, including the position and geometry of unsaturation in the side chains, as well as evaluation of their bioactivity (see below). Compounds 1–8 at 10 μg/disc inhibited the growth of a bacterium of the phylum Bacteroidetes, T. maritimum (Table 2). Overall, alkylquinolones 1–6 were more potent than 7

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• catalytic asymmetric construction of the cyclic enaminone-based 3-substituted 3-amino-2-oxindole scaffold with potential bioactivity on the basis of enantioselective additions of cyclic enaminones to N-Boc-isatin imines [40]. As shown in Scheme 7, the addition of dimedone-derived enaminones 22 to a variety

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• significantly reduced in the presence of a base mismatch. This specificity in binding suggested that such oligonucleotides should be promising sterically blocking antisense agents as their RNA targets were not digested by RNAse H. This anticipated bioactivity was confirmed in whole cell assays without the

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• were introduced on polyfused heterocycles 7 because these were shown to often have a positive effect on the bioactivity (see compounds in Figure 1). Starting with 2-azido-4-bromobenzaldehyde (1b), we were able to prepare two brominated tetracyclic derivatives 7g and 7h. In the same way, we were also