Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• can be further modified by tailoring enzymes, but the core structure can be inferred from the organization of the biosynthetic genes and the modular architecture of the associated proteins [7][8]. Terpene biosynthesis has a very different logic. Five-carbon units called isoprenes are joined to create

Emission and biosynthesis of volatile terpenoids from the plasmodial slime mold Physarum polycephalum

• Xinlu Chen,
• Tobias G. Köllner,
• Wangdan Xiong,
• Guo Wei and
• Feng Chen

Beilstein J. Org. Chem. 2019, 15, 2872–2880, doi:10.3762/bjoc.15.281

• and similar residues, respectively. B) Intron/exon organization of the four PpolyTPS genes. Boxes and lines indicate exons and introns, respectively. PpolyTPS1 and PpolyTPS4 have terpene synthase activities. A) GC chromatogram of sesquiterpenes produced by recombinant PpolyTPS1 incubated with FPP. 2

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• photochemical and binding characterization of compounds 3e, 4d, 6b and 6d–i. Structure and results of functional characterization of compounds 3e, 4d, 6b and 6d–h. Supporting Information Supporting Information File 618: Experimental part. Acknowledgements All authors acknowledge the Netherlands Organization

Perspective isomorphs – a new classification of molecular structures based on artistic and chemical concepts

• Jannis Neumann,
• Ansgar Schnurr and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2019, 15, 2319–2326, doi:10.3762/bjoc.15.224

• group of molecules that are congruent in a hypothetical view with the human eye and from a defined perspective. Thus, the spatial organization of their incorporated atoms would not be distinguishable for the human mode of perception. Such molecules are called perspective isomorphs of a specific PI class

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

Host–guest interactions between p-sulfonatocalix[4]arene and p-sulfonatothiacalix[4]arene and group IA, IIA and f-block metal cations: a DFT/SMD study

• Valya K. Nikolova,
• Cristina V. Kirkova,
• Silvia E. Angelova and
• Todor M. Dudev

Beilstein J. Org. Chem. 2019, 15, 1321–1330, doi:10.3762/bjoc.15.131

• is shown that the metal cations induce different pre-organization of the calixarene structure upon binding. The preferred binding site for the guest metal cations is the plane of the upper rim (with p-sulfonato groups), i.e., the sulfonate groups of hosts serve as anchoring points for the positively

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

• domain organization of the two corresponding biosynthetic assembly lines further indicated that Massilia sp. NR 4-1 does not produce micacocidin, but a derivative of this secondary metabolite. The isolation of siderophores from microorganisms is usually straightforward due to their iron-dependent

• array detector. In total, 12.0 mg of 1 were isolated. Massiliachelin (1) pale yellow solid; UV (MeOH) λmax (log ε): 356 (3.06), 280 (4.18), 228 (4.64) nm; 1H and 13C NMR, Table 1; HRESIMS m/z: [M + H]+, calcd for C23H35N2O4S2, 467.2033; found, 467.2033. A) Organization of the micacocidin-type gene

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• (terpyridines; Figure 1c) ligands [49]. The model systems depicted in Figure 1 are constructed using metals like Pd(II) or Pt(II) ions for square planar geometry, Cu(I) or Ag(I) ions for tetrahedral geometry and Co(II)/Cu(II)/Fe(II)/Zn(II)/Hg(II) for octahedral organization [50]. In Figure 2, Busch’s first

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• ). The World Health Organization estimates that this neglected tropical disease causes between 1–2 million new cases annually [4]. Leishmaniasis manifests into three different forms, cutaneous, mucosal, or visceral, depending on parasite species, host immune system and location of infection [5

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• mild conditions, hydrogenolysis of the benzyl ester group to the carboxylic acid and hydrogenation of the C=C double bonds at the silicon atoms (Scheme 7). The ability of the obtained derivatives, in particular the carboxylic acids, to generate nanostructured materials through self-organization

Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce

• Hidekazu Komatsu,
• Takashi Shirakawa,
• Takeo Uchiyama and
• Tsutomu Hoshino

Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27

• Administration, Institute of Vegetable and Floriculture Science, National Agriculture and Food Research Organization, 3-1-1 Kannondai, Tsukuba, Ibaraki 305-8519, Japan 10.3762/bjoc.15.27 Abstract Pseudomonas cichorii, which causes varnish spots on lettuce and seriously damages lettuce production during the

• samples were allowed to stand for 3 days to estimate the activities, as shown in Supporting Information File 1, Figure S19B. Isolation of cichorinotoxin Pseudomonas cichorii isolate YM8705 has been deposited in NARO Genebank as MAFF730229 (NARO: National Agricultural and Food Research Organization). P

New standards for collecting and fitting steady state kinetic data

• Kenneth A. Johnson

Beilstein J. Org. Chem. 2019, 15, 16–29, doi:10.3762/bjoc.15.2

• a smaller substrate than the preferred one. The induced-fit model proposes a two-step binding pathway in which the substrate first binds to an open form of the enzyme and then the enzyme closes leading to tighter binding and organization of catalytic residues. For decades debate raged as to whether

• step. The substrate binds weakly and then the enzyme closes. If the substrate shows the right geometry (structurally and electrostatically) the closed state is stabilized and organization of catalytic residues leads to fast catalysis. If the substrate is not the right size and shape, the enzyme fails

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• ][4][5]. However, the World Health Organization (WHO) reported 1.6 million fatalities worldwide from tuberculosis in 2017, with more than 10 million annual new cases, and an overall estimated global burden of almost 1.7 billion latently infected people [2]. The fight against this primarily pulmonary

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

• knowledge on their biosynthesis, the underlying gene organization, as well as their function in many bacteria [11][12][13]. In the Roseobacter group, AHLs are involved, e.g., in antibiotic production [9] or cell differentiation [10]. Although many other bacterial signalling compounds must exist, only few of

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• death according to the World Health Organization [1]. The serendipitous discovery of penicillin and its introduction into the clinic in the first half of the 20th century gave rise to the “Golden Age” of antibiotics discovery and have unquestionably represented one of the most important achievements in

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• Organization (WHO) has published a priority list for pathogens with urgent need for novel treatment options and carbapenem-resistant P. aeruginosa was ranked in the highest category ‘critical’ [12]. One of the main problems we face regarding this Gram-negative bacterium is that it shows a prominent ability to

Transition metal-free oxidative and deoxygenative C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyl lithium as an efficient synthetic approach to azaheterocyclic carboranes

• Lidia A. Smyshliaeva,
• Mikhail V. Varaksin,
• Pavel A. Slepukhin,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2018, 14, 2618–2626, doi:10.3762/bjoc.14.240

• 1-oxide; nucleophilic substitution of hydrogen (SNH); Introduction Dicarbadodecaboranes (carboranes) are known to be 3D polyhedral clusters with a special type of structural organization, relative thermal and chemical stabilities, as well as unique physicochemical properties [1][2][3]. The

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

• -Braunschweig, Germany Department of Pharmacy, Saarland University, Saarbrücken, Germany 10.3762/bjoc.14.239 Abstract The rapid development of antimicrobial resistance is threatening mankind to such an extent that the World Health Organization expects more deaths from infections than from cancer in 2050 if

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• ; supramolecular chemistry; tetrathiafulvalene; Introduction Undoubtedly, the exploration of nature’s molecular machines in the last century led to a paradigm change of how we think about working and organization processes on the molecular level [1][2][3]. Inspired by the way how energy and concentration

• . A strategy to stabilize the mixed-valence and radical-cation dimer even at room temperature and to overcome the entropic penalty of their formation is to facilitate a spatial proximity of two or more TTF units by a suitable covalent link [37][38]. This pre-organization can also be generated in

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• chemical calculations were done in several steps: selection of optimal conformers; organization of initial complex geometry; complex optimization procedure. The conformers search procedure has been done only for calix[4]arene’s triazolyl substituents due to complexity of the whole molecule. Conformers of

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• and their optimization at various locations of an organization can become reproducible upon integration through such platforms. While the concept of a unified synthesis platform looks fascinating and useful to reach the targets like ‘Dial-a-molecule’ [45], in reality, it can be very challenging. Some

• made keeping the interest of individual or organization for future. These approaches show the unique and promising ways to make the unified platform to realize the concepts like dial a molecule. Realising the concept of a unified flow synthesis platform possesses some challenges but those can be taken

Selective carboxylation of reactive benzylic C–H bonds by a hypervalent iodine(III)/inorganic bromide oxidation system

• Toshifumi Dohi,
• Shohei Ueda,
• Kosuke Iwasaki,
• Yusuke Tsunoda,
• Koji Morimoto and
• Yasuyuki Kita

Beilstein J. Org. Chem. 2018, 14, 1087–1094, doi:10.3762/bjoc.14.94

• Toshifumi Dohi Shohei Ueda Kosuke Iwasaki Yusuke Tsunoda Koji Morimoto Yasuyuki Kita College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan. Tel: +81-77-561-4908, Research Organization of Science and Technology, Ritsumeikan University, 1-1-1

• work was supported by a Grant-in-Aid for Scientific Research (A) to Y.K. from JSPS and a Grant-in-Aid for Encouragement of Young Scientists (A) and Scientific Research (C) to T.D. from JSPS, and Ritsumeikan Global Innovation Research Organization (R-GIRO) project. T.D. thanks the research fund of 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

• ; Introduction Current cancer chemotherapy Cancer is one of the leading causes of death globally behind the heart and circulatory disorders based on statistics of World Health Organization (WHO) [1]. Among all different types of cancer, the most fatal for males are lung and prostate cancer, while for females are

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• -steroidal drug with anti-inflammatory activity for the treatment of rheumatoid arthritis (RA) in patients with cardiovascular disease [7][8][9]. The World Health Organization has identified HCQ (1) as an essential antimalarial medication for a basic healthcare system, but global access to HCQ (1) has been

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

• extent of secondary chiral organization, thus also allowing a monitoring by ECD spectroscopy [16][17]. The non-degenerate coupled oscillator mechanism is also responsible for generating ECD signals in correspondence with electronic transitions of achiral chromophores surrounded by a chiral environment

• organization of DNA/RNA chromophores (base pairs) in a helical structure, ECD is primarily sensitive to the secondary structure of various nucleic acids and provides characteristic ECD spectra of nucleic acids as a result of base sequence and experimental conditions (see chapter 2.1.). As an example of how the