In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5-a]pyrimidines

• Irina G. Tkachenko,
• Sergey A. Komykhov,
• Vladimir I. Musatov,
• Svitlana V. Shishkina,
• Viktoriya V. Dyakonenko,
• Vladimir N. Shvets,
• Mikhail V. Diachkov,
• Valentyn A. Chebanov and
• Sergey M. Desenko

Beilstein J. Org. Chem. 2019, 15, 2390–2397, doi:10.3762/bjoc.15.231

• . Crystal data: The crystal structure of compound 9a was measured on an Xcalibur-3 diffractometer (graphite monochromated Mo Kα radiation, CCD detector, ω-scanning). The structure was solved by the direct method using the SHELXTL package [34][35]. Full-matrix least-squares refinement against F2 in

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

• mutagenesis have exciting applications for the sustainable production of high value bioactive substances. Keywords: biotechnology; CotB2; crystal structure; cyclooctatin; diterpene; reaction mechanism; terpene synthase; Introduction Terpenes represent one of the most diverse groups of natural biomolecules

• subsequent cyclization unlikely. Crystal structure of CotB2wt·Mg2+3·F-Dola resembles the closed, active conformation The structure of CotB2wt·Mg2+3·F-Dola has been obtained by co-crystallization of CotB2wt and FGGDP (PDB-ID 6GGI; [37]), representing the closed, active conformation. Fluorinated substrates

• -crystallized with AHD, a compound that mimics the diphosphate group of GGDP and acts as a suicide inhibitor. The crystal structure of CotB2wt·Mg2+3·AHD (PDB-ID 6GGJ; [37]) confirmed the active site architecture as observed in the structure of CotB2wt·Mg2+3·F-Dola and more importantly, that the folding of the C

Small anion-assisted electrochemical potential splitting in a new series of bistriarylamine derivatives: organic mixed valency across a urea bridge and zwitterionization

• Keishiro Tahara,
• Tetsufumi Nakakita,
• Alyona A. Starikova,
• Takashi Ikeda,
• Masaaki Abe and
• Jun-ichi Kikuchi

Beilstein J. Org. Chem. 2019, 15, 2277–2286, doi:10.3762/bjoc.15.220

• . Such N–H···F hydrogen-bond formation was also reported for other urea derivatives with PF6− as counteranion in the solid state [54][55]. The N···F distance of 2.85 Å in 1b+–PF6− is slightly longer than that observed in the crystal structure of a silver complex having a pyridyl urea ligand (2.67 and

Characterization of two new degradation products of atorvastatin calcium formed upon treatment with strong acids

• Jürgen Krauß,
• Monika Klimt,
• Markus Luber,
• Peter Mayer and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2085–2091, doi:10.3762/bjoc.15.206

• NMR spectroscopy, HRMS data and X-ray crystal structure analysis. Keywords: atorvastatin; crystal structure; cyclization; degradation products; fragmentation; stress test; Introduction Over the past decades, the general trend toward globalization of the supply chains for active pharmaceutical

• isopropyl residue, originally located at C-2 of the pyrrole, is shifted to C-3, rendering the annulated, tetrasubstituted pyrrole 6. The structure of 6 was confirmed by X-ray crystal structure analysis. However, most likely cleavage of the carboxanilide moiety (compare formation of 7 from atorvastatin with

• elucidated by NMR and crystal structure analysis. The bridged tricyclic product 6 was formed with concentrated hydrochloric acid, whereas lactone 7 resulted from treatment with concentrated sulfuric acid. We propose mechanisms for the formation of the novel artefacts 6 and 7 here. But it has to be mentioned

Synthesis of benzo[d]imidazo[2,1-b]benzoselenoazoles: Cs₂CO₃-mediated cyclization of 1-(2-bromoaryl)benzimidazoles with selenium

• Mio Matsumura,
• Yuki Kitamura,
• Arisa Yamauchi,
• Yoshitaka Kanazawa,
• Yuki Murata,
• Tadashi Hyodo,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2019, 15, 2029–2035, doi:10.3762/bjoc.15.199

• was fully characterized by 1H and 13C NMR spectroscopy and HRMS, and further confirmed by single-crystal X-ray diffraction (XRD) analysis. The ORTEP drawing and packing structure of 2a obtained from the single crystal XRD analysis are illustrated in Figure 1. The crystal structure contained two

• . Cyclization of 1-(2-bromophenyl)benzimidazoles with chalcogen elements.a Absorption spectroscopy dataa. Supporting Information Supporting Information File 401: Experimental details and analytical data, copies of absorption and NMR spectra. Supporting Information File 402: X-ray crystal structure of 2a

Fluorinated azobenzenes as supramolecular halogen-bonding building blocks

• Esther Nieland,
• Oliver Weingart and
• Bernd M. Schmidt

Beilstein J. Org. Chem. 2019, 15, 2013–2019, doi:10.3762/bjoc.15.197

• to facilitate readability. a) Space-filling model of U1···A2. The kinked alignment of both the lutidine units of U1 and the azobenzenes A2 can be seen. b) Part of the X-ray crystal structure showing the halogen bonding azobenzene A2 in detail. Selected bond lengths: N3–I1 2.7810(2), I2–N4 2.816(2) Å

Installation of -SO₂F groups onto primary amides

• Jing Liu,
• Shi-Meng Wang,
• Njud S. Alharbi and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 1907–1912, doi:10.3762/bjoc.15.186

• introduced into the stirred reaction mixture by slowly bubbling from a balloon, and the mixture was allowed to stir at 50 °C for 12 h. Isolated yields. a50 °C, 18 h. Amide resonance model and X-ray single crystal structure of 4e (CCDC 1906002). The proposed reaction mechanism. Optimization of the reaction

Tautomerism as primary signaling mechanism in metal sensing: the case of amide group

• Vera Deneva,
• Georgi Dobrikov,
• Aurelien Crochet,
• Daniela Nedeltcheva,
• Katharina M. Fromm and
• Liudmil Antonov

Beilstein J. Org. Chem. 2019, 15, 1898–1906, doi:10.3762/bjoc.15.185

• stabilization in acetonitrile. The explanation for the sudden stabilization of 6K was found by X-ray measurements of its crystal, obtained in acetonitrile. The crystal structure of 6, shown in Figure 3, clearly indicates that the K form is stabilized through the formation of linear intermolecular associates. It

• exists exclusively as H-aggregates as in the crystal structure. The absorption spectra of 6 in acetonitrile upon addition of Mg(ClO4)2 are shown in Figure 4. A clear isosbestic point can be seen in the area where the enol tautomer does not absorb, indicating that the tautomeric equilibrium is shifted

• using Least Squares minimization. Crystal structure determination of 6 Crystal data for C20H19N3O2 (M =333.38 g/mol): monoclinic, space group P21/c (no. 14), a = 5.5438(8) Å, b = 17.850(2) Å, c = 17.184(3) Å, β = 91.719(12)°, V = 1699.7(4) Å3, Z = 4, T = 250(2) K, μ(Cu Kα) = 0.691 mm−1, dcalc = 1.303 g

Inherent atomic mobility changes in carbocation intermediates during the sesterterpene cyclization cascade

• Hajime Sato,
• Takaaki Mitsuhashi,
• Mami Yamazaki,
• Ikuro Abe and
• Masanobu Uchiyama

Beilstein J. Org. Chem. 2019, 15, 1890–1897, doi:10.3762/bjoc.15.184

• terpene cyclase active site [3][5][6]. Although many terpene cyclases are known [6][7][8][9][10], it is still challenging to identify the precise initial conformation of the oligoprenyl diphosphate substrate in the active site, even by X-ray crystal structure determination. This is because the substrate

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• gave 16 in 87% yield [26][27]. The absolute stereochemistry of 16 was confirmed by crystal structure analysis [72] and the specific rotation [28] of 17. Centimeter-long prismatic single crystals of 17 were obtained by slow evaporation of a petroleum solution. Starting from 9, we tested several

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• innate immunity through macrophage response as well as to more distally affect adaptive immunity through the production of antigen-specific T cells [5]. MDP binding to NOD2 has been confirmed [6] as well as the crystal structure of NOD2 in the inactive ADP-bound state [7]. MDP is the structural fragment

Complexation of 2,6-helic[6]arene and its derivatives with 1,1′-dimethyl-4,4′-bipyridinium salts and protonated 4,4'-bipyridinium salts: an acid–base controllable complexation

• Jing Li,
• Qiang Shi,
• Ying Han and
• Chuan-Feng Chen

Beilstein J. Org. Chem. 2019, 15, 1795–1804, doi:10.3762/bjoc.15.173

• G1, (c) free G1, (d) H4 with 1.0 equiv G1, (e) free H4. [H1]0 = [H4]0 = [G1]0 = 2.0 mM. Partial 1H NMR spectra (400 MHz, CD2Cl2, 298 K) of (a) free H1, (b) H1 with 1.0 equiv G4, (c) free G4, (d) H4 with 1.0 equiv G4, (e) free H4. [H1]0 = [H4]0 = [G4]0 = 2.0 mM. Crystal structure of complex H1·G1. (a

• ) Top view, (b) side view, and (c) packing viewed along c-axis. Blue lines denote the non-covalent interactions between H1 and G1. Solvent molecules and hydrogen atoms not involved in the non-covalent interactions were omitted for clarity. Crystal structure of complex H5·G1. (a) Top view, (b) side view

Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

• Aleksandr S. Krylov,
• Artem A. Petrosian,
• Julia L. Piterskaya,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159

• coupling constant of 2JНР ≈ 20 Hz. In the 13С NMR spectra, the methylene carbon resonated as a doublet at δ 23.5 ppm (JCP = 143 Hz). In addition, the structures of triazolopyridines 3–8 were unambiguously confirmed by the crystal structure of 5b. Remarkably, the presence of a nitro group in the pyridine

Molecular basis for the plasticity of aromatic prenyltransferases in hapalindole biosynthesis

• Takayoshi Awakawa and
• Ikuro Abe

Beilstein J. Org. Chem. 2019, 15, 1545–1551, doi:10.3762/bjoc.15.157

• AmbP1 and AmbP3 functions, elucidated through their X-ray crystal structures. The knowledge presented here will contribute to the understanding of aromatic PTase reactions and will enhance their uses as biocatalysts. Keywords: crystal structure; cyanobacteria; Friedel–Crafts reaction; hapalindole

• (Figure 2B). Remarkably, AmbP3 also accepts (10S)-hapalindole A (HA), and transfers the dimethylallyl group onto the C-2 carbon of hapalindole A in normal prenylation mode to yield compound 3 (Figure 2B). X-ray crystal structure analysis of AmbP1 To understand the effect of Mg2+ ions on the AmbP1 reaction

• PTases that utilize a Mg2+ ion to reorganise the active site cavity to control the regiospecificity of the prenylation reaction. X-ray crystal structure analysis of AmbP3 The crystal structures of AmbP3 complexed with DMSPP/hapalindole U (HU structure) and A (HA structure) were each solved at 2.00 Å [14

A heteroditopic macrocycle as organocatalytic nanoreactor for pyrroloacridinone synthesis in water

• Piyali Sarkar,
• Sayan Sarkar and
• Pradyut Ghosh

Beilstein J. Org. Chem. 2019, 15, 1505–1514, doi:10.3762/bjoc.15.152

• ) SEM image and (c) TEM image showing the nanoranged particle distribution of the macrocycle. Dependence of the yield of compound 4a on the reaction time using BATA-MC. Yields of product 4a at different catalyst loading. X-ray single crystal structure of 4d (CCDC 1898008). Representation of BATA-MC

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

• and 2, the hitherto most truncated derivatives of AbC. Results and Discussion An initial evaluation of the truncation strategy was made by assessing the potential efficiency of binding to the target by modeling. Accordingly, the crystal structure of ADC synthase (PDB ID: 1K0E) [19] was used for

• docking of known and proposed ligands. The crystal structure contains a tryptophan molecule in the active site. Restrained molecular dynamics [20][21] was employed to position the active site cysteine (Cys-263) in a position that would allow covalent binding of the ligands in the active site. The

2,3-Dibutoxynaphthalene-based tetralactam macrocycles for recognizing precious metal chloride complexes

• Li-Li Wang,
• Yi-Kuan Tu,
• Huan Yao and
• Wei Jiang

Beilstein J. Org. Chem. 2019, 15, 1460–1467, doi:10.3762/bjoc.15.146

• butyl methylene group next to the oxygen atoms. A single crystal (Figure 2) of 1, which was suitable for X-ray crystallography, was obtained by slow evaporation of its solution in CH3CN. The crystal structure clearly shows that 1 adopts a flattened chair conformation with the two naphthalenes in

• (500 MHz, CDCl3) of a) 1 at 298 K, b) 1 at 223 K, and c) 2 at 298 K. Two different views of the X-ray single crystal structure of 1 obtained from its CH3CN solution. Partial 1H NMR spectra (500 MHz, CDCl3, 0.5 mM, 298 K) of 1 and the equimolar mixture with TBA[AuCl4]. ESI mass spectrum of complex AuCl4

Introduction of an isoxazoline unit to the β-position of porphyrin via regioselective 1,3-dipolar cycloaddition reaction

• Xiujun Liu,
• Xiang Ma and
• Yaqing Feng

Beilstein J. Org. Chem. 2019, 15, 1434–1440, doi:10.3762/bjoc.15.143

• reaction trajectory, in which only the product with a link between the 5-position of the isoxazoline and the β-position of porphyrin was observed. The isoxazoline-porphyrins 3a,b have been characterized by absorption, emission, 1H NMR and mass spectra. Later, the crystal structure of 3a was obtained and

• regioselectivity and reaction trajectory of the 1,3-dipolar cycloaddition reaction by steric hindrance. The obtained novel isoxazoline-substituted porphyrin derivatives 3a,b have been characterized by absorption, emission, NMR and mass spectrometry. In addition, the crystal structure of 3a is discussed. Results

• trimethylphenyl group) in CDCl3 (500 MHz, 25 °C). The representative dimeric structure of 3a according to the crystal structure (a) and enantiomeric dimer structure in crystal (b–d, the phenyl group at meso-positions and 2,6-dichlorophenyl group were omitted for the sake of clarity). The distances of Zn–O (c) and

Selenophene-containing heterotriacenes by a C–Se coupling/cyclization reaction

• Pierre-Olivier Schwartz,
• Sebastian Förtsch,
• Astrid Vogt,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2019, 15, 1379–1393, doi:10.3762/bjoc.15.138

• single crystal structure analysis were compared to the X-ray powder diffraction spectra (Figures S10, S11 and S12, in Supporting Information File 1). Whereas no correlation of the main peaks was found for DTT 1, DTS 2 showed a better relationship between the powder and single crystal derived powder

• crystal structure analysis. XRD plots of DST 2 and DSS 4 showed strong diffusion scattering vs signal intensity which we assign to a high degree of amorphous phases. The crystallite sizes determined were quite similar for 1, 2, and 3 (66 nm, 76 nm, and 72 nm), respectively, except for DSS 4 which were

• the crystal structure analysis. The analysis of the theoretical calculations gave also insight into the electronic properties of the heterotriacene series. The energies of the calculated frontier orbitals and electronic transitions are summarized in Table 3. In this respect, the energy of the HOMO

One-pot activation–alkynylation–cyclization synthesis of 1,5-diacyl-5-hydroxypyrazolines in a consecutive three-component fashion

• Christina Görgen,
• Katharina Boden,
• Guido J. Reiss,
• Walter Frank and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 1360–1370, doi:10.3762/bjoc.15.136

• details on the attempted dehydrative aromatization of compound 5b, and NMR spectra of the compounds 5, and for summaries on the crystal structure analyses of 5a, 5r, and 6a see Supporting Information File 1. Supporting Information File 256: Experimental details, copies of NMR spectra and crystallographic

Formation of an unexpected 3,3-diphenyl-3H-indazole through a facile intramolecular [2 + 3] cycloaddition of the diazo intermediate

• Andrew T. King,
• Hugh G. Hiscocks,
• Lidia Matesic,
• Mohan Bhadbhade,
• Roger Bishop and
• Alison T. Ung

Beilstein J. Org. Chem. 2019, 15, 1347–1354, doi:10.3762/bjoc.15.134

• the indazole ring. The ambiguity was overcome through the X-ray structural analysis of the compound. The single crystals were easily obtained by recrystallisation from CH2Cl2. Crystal structure analysis The X-ray crystal analysis revealed that the product was not the diazonium intermediate 7, but

• crystal structure of 8 involves edge–face Ar–H···π, face–face π···π, bifurcated OCH2–H···N, plus edge–edge centrosymmetric Ar–H···H–Ar interactions. These rather uncommon examples of dihydrogen contact assemble as infinite tapes along the a direction. Experimental Materials and physical measurements All

• refinements were carried out using SHELXL-2014 [35] through Olex2 [36] suite of software. The non-hydrogen atoms were refined anisotropically. Molecular graphics were generated using Mercury [37]. Key crystallographic data and refinement details are presented in Table 1. Crystal structure data

Synthesis of dipolar molecular rotors as linkers for metal-organic frameworks

• Sebastian Hamer,
• Fynn Röhricht,
• Marius Jakoby,
• Ian A. Howard,
• Xianghui Zhang,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 1331–1338, doi:10.3762/bjoc.15.132

• coupling in a low yield of 10% alongside with phthalocyanine byproducts. The triisopropylsilyl-protected derivative 12b could be obtained in a slightly higher yield of 21%, presumably due to the bulkier TIPS-groups. A crystal structure of this compound was obtained (see Supporting Information File 2). To

Bambusuril analogs based on alternating glycoluril and xylylene units

• Tomáš Lízal and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2019, 15, 1268–1274, doi:10.3762/bjoc.15.124

• signals. X-ray crystal structure of 1b-1 (left), layered structure of crystal packing (right). Reaction of 2,4-dimethylglycoluril and m-xylylene dibromide. Supporting Information Supporting Information File 273: MS and NMR spectra, computational details and crystallographic data for macrocycles 1a and 1b

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

• exceptions, S. rubrolavendulae MJM4426 and S. collinus Tü 365, members of the other two phylogenomic clades that also present a cyclooctat-9-en-7-ol synthase. Cyclooctat-9-en-7-ol synthase (CotB2) from S. melanosporofaciens was the first bacterial type I diterpene cyclase characterised [40] and its crystal

Molecular recognition using tetralactam macrocycles with parallel aromatic sidewalls

• Dong-Hao Li and
• Bradley D. Smith

Beilstein J. Org. Chem. 2019, 15, 1086–1095, doi:10.3762/bjoc.15.105

• shown that members of this tetralactam family are effective receptors for saccharides in water [65]. As shown by the X-ray crystal structure in Figure 7a, water-soluble versions of tetralactam B can nicely accommodate β-glucopyranose within the cavity [66]. There is a combination of hydrogen bonding

• inside tetralactam B. In (b) is an X-ray crystal structure of a complex comprised of a squaraine guest encapsulated by tetralactam B (X = CH, Z = t-Bu) in a flattened chair conformation [33]. In (c) and (d) are calculated structures (semiempirical, PM7) of complexes comprised of a thiosquaraine or

• croconaine, respectively, encapsulated by tetralactam B (X = CH, Z = t-Bu) in a boat conformation [57][58][59]. In (e) is an X-ray crystal structure of an azaacene guest encapsulated by tetralactam B (X = N, Z = H) in a boat conformation [25]. (a) Shape and electrostatic comparison of squaraine C4O2 core