Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• with a highly substituted oxazole skeleton with a thiol group is expected to have potential synergetic bioactivity [70]. During the exploration of the reactivity of azidochalcones with thiocyanate in the presence of the oxidizing agent, 1i was chosen as the model α-azidochalcone to react with potassium

The biomimetic synthesis of balsaminone A and ellagic acid via oxidative dimerization

• Sharna-kay Daley and
• Nadale Downer-Riley

Beilstein J. Org. Chem. 2020, 16, 2026–2031, doi:10.3762/bjoc.16.169

• dimerization to the dimeric polyphenolic acid 11, followed by intramolecular cyclization to yield ellagic acid (5, Scheme 2) [20]. Because of the bioactivity of both natural products, there have been previous investigations of the synthesis of balsaminone A (4) [21][22] and ellagic acid (5) [23]. In our

Three new O-isocrotonyl-3-hydroxybutyric acid congeners produced by a sea anemone-derived marine bacterium of the genus Vibrio

• Dandan Li,
• Enjuro Harunari,
• Tao Zhou,
• Naoya Oku and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1869–1874, doi:10.3762/bjoc.16.154

• describe the isolation, structure elucidation, including the absolute configuration, and bioactivity of 1–4. Results and Discussion The producing strain was cultured in a sea water-based medium and then extracted with n-BuOH. The extract was successively fractionated by silica gel chromatography using a

Antibacterial scalarane from Doriprismatica stellata nudibranchs (Gastropoda, Nudibranchia), egg ribbons, and their dietary sponge Spongia cf. agaricina (Demospongiae, Dictyoceratida)

• Cora Hertzer,
• Stefan Kehraus,
• Nils Böhringer,
• Fontje Kaligis,
• Robert Bara,
• Dirk Erpenbeck,
• Gert Wörheide,
• Till F. Schäberle,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2020, 16, 1596–1605, doi:10.3762/bjoc.16.132

• accumulate 12-deacetoxy-4-demethyl-11,24-diacetoxy-3,4-methylenedeoxoscalarin from Spongia cf. agaricina, but to pass it on to the egg ribbons as well. This, in addition to its bioactivity, might suggest a biological role, either as protection against predation, fouling, or in the reproductive cycle, as

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

• ) and PubChem (NIH). Both focus on characterising drug-like molecules and providing information to the public domain. The former is a manually curated database of bioactive molecules, which aims to bring together chemical, bioactivity and genomic data to aid the translation of genomic information into

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

• for bioactive compounds are required, such as the bacterial genera Xenorhabdus or Photorhabdus. In these strains, fabclavines are widely distributed SMs with a broad-spectrum bioactivity. Fabclavines are hybrid SMs derived from nonribosomal peptide synthetases (NRPS), polyunsaturated fatty acid (PUFA

• . budapestensis and X. szentirmaii, and a 50 kb biosynthesis gene cluster (BGC) was identified to be responsible for their formation (Figure 1) [20]. These compounds were of special interest because of their broad-spectrum bioactivity against Gram-positive and -negative bacteria, fungi, and protozoa [20][21

• zeae [23][24]. They also exhibit broad-spectrum bioactivity, but their biosynthesis includes an additional processing step, executed by an acylpeptide hydrolase, which could not be detected in the fabclavine BGC [20][25]. To date, 10 full-length fabclavines could be identified, and the structure of

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

• other memory impairments, namely (−)-galanthamine (13), has attracted great interest for its structural complexity and specific bioactivity. The total synthesis of compound 13, described by Brown et al. [81], involved an enyne ring-closing metathesis and a Heck cross-coupling as the key reactions for

Opening up connectivity between documents, structures and bioactivity

• Christopher Southan

Beilstein J. Org. Chem. 2020, 16, 596–606, doi:10.3762/bjoc.16.54

• “D“ where a bioactivity “A” with a quantitative result “R” (e.g., an IC50) is reported for chemical structure “C” that modulates (e.g., inhibits) a protein target “P”. A useful shorthand for this connectivity thus becomes DARCP. The problem at the core of this article is that the community has spent

• accelerate the progress and impact of medicinal chemistry. To achieve this the community needs to increase the outward flow of experimental results locked-up in millions of published PDFs into structured open databases that explicitly capture the connectivity between structures, documents and bioactivity

• connectivity is out of scope for this article. Bioactivity: This covers a wide spectrum of assay read-outs but with a focus on in vitro, in cellulo, in vivo and in clinico. Ideally this should also include low or inactive analogues which are crucial for SAR elucidation but documents are (understandably) biased

Aerobic synthesis of N-sulfonylamidines mediated by N-heterocyclic carbene copper(I) catalysts

• Faïma Lazreg,
• Marie Vasseur,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2020, 16, 482–491, doi:10.3762/bjoc.16.43

• : catalysis; copper; copper catalysis; N-heterocyclic carbene; solvent-free; sulfonylamidines; Introduction Amide derivatives represent a ubiquitous molecular construct in chemistry [1][2][3]. This structural motif favours rearrangements that lead to high reactivity and associated bioactivity [4][5]. Indeed

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• that the physicochemical properties remained widely unchanged. However, further studies must be undertaken in order to gain knowledge on the bioactivity of this SeCF3-containing analog. In situ synthesis of trifluoromethylselenolated compounds using copper complexes One-pot procedures that rely on the

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