Fluorine-containing substituents: metabolism of the α,α-difluoroethyl thioether motif

• Andrea Rodil,
• Alexandra M. Z. Slawin,
• Nawaf Al-Maharik,
• Ren Tomita and
• David O’Hagan

Beilstein J. Org. Chem. 2019, 15, 1441–1447, doi:10.3762/bjoc.15.144

• into diethyl ether and dichloromethane (DCM) and then carrying out HPLC analyses. Incubation of thioether 4 with C. elegans led to the identification of three metabolites 6–8 as illustrated in Scheme 1. These were isolated by semi-preparative HPLC. Two of these (6 and 7) displayed an AB system in the

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

• -generated nitrile oxide, which showed inferior selectivity and afforded regio-/stereoisomers [43]. NMR analysis assisted the identification of various isomeric isoxazoline-linked chlorin products. Here, we would like to report an artificial vinylporphyrin 2, which has been designed to control the

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

• production and complexing properties [15]. Therefore, we decided to initially focus our genome mining efforts on the micacocidin-type cluster in Massilia sp. NR 4-1. Here, we report the outcome of this study, which led to the identification of a previously unrecognized agrochelin epimer and, furthermore

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

• ). These exceptions may indicate horizontal gene transfer of the genes encoding for these enzymes. The sesquiterpene 7-epi-α-eudesmol synthase from S. viridochromogenes DSM 40736 has been chemically characterised in vivo by heterologous expression in E. coli BL21 and identification of the product in

Precious metal-free molecular machines for solar thermal energy storage

• Meglena I. Kandinska,
• Snejana M. Kitova,
• Vladimira S. Videva,
• Stanimir S. Stoyanov,
• Stanislava B. Yordanova,
• Stanislav B. Baluschev,
• Silvia E. Angelova and
• Aleksey A. Vasilev

Beilstein J. Org. Chem. 2019, 15, 1096–1106, doi:10.3762/bjoc.15.106

• -system [9] with a triplet–triplet annihilation photon energy upconversion system (TTA-UC) [10][11] an effective utilization of sub-bandgap photons is possible [12][13]. Nevertheless, the identification of a precious metal-free MOST system utilizing the visible part of the sun spectrum remains a

• improvements and brings the scientists nearer to the identification of the “perfect” MOST system. In this connection we identified crown ether-containing styryl dyes [14][15] as promising substances due to their ability to undergo trans-to-cis photoisomerization (E/Z) with very high quantum yields. In addition

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• excellent diastereoselectivities (1:19 and 1:99 α:β ratio, respectively). Hydroboration of the glucose enol ether 6 afforded a mixture of both diastereomers (1:2.3 α:β ratio) in good yield (43% β and 18% α isolated yields, respectively). Identification of the diastereomers was accomplished by NOESY

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• (path A) and an hypothetical alternative mechanism via an initial 1,6-cyclisation (path B). Alternative mechanistic and reaction arrows belonging to branching points are shown in red. HcS product identification by retention indices. Supporting Information Experimental details for gene cloning, gene

An anomalous addition of chlorosulfonyl isocyanate to a carbonyl group: the synthesis of ((3aS,7aR,E)-2-ethyl-3-oxo-2,3,3a,4,7,7a-hexahydro-1H-isoindol-1-ylidene)sulfamoyl chloride

• Aytekin Köse,
• Aslı Ünal,
• Ertan Şahin,
• Uğur Bozkaya and
• Yunus Kara

Beilstein J. Org. Chem. 2019, 15, 931–936, doi:10.3762/bjoc.15.89

• exact configuration was determined by X-ray crystal analysis. We explain the mechanism of product formation supported by theoretical calculations. Keywords: addition reaction; chlorosulfonyl isocyanate; sulfamoyl chloride; theoretical calculations; Introduction Since its identification in 1959 [1

Strong hyperconjugative interactions limit solvent and substituent influence on conformational equilibrium: the case of cis-2-halocyclohexylamines

• Camila B. Francisco,
• Cleverton S. Fernandes,
• Ulisses Z. de Melo,
• Roberto Rittner,
• Gisele F. Gauze and
• Ernani A. Basso

Beilstein J. Org. Chem. 2019, 15, 818–829, doi:10.3762/bjoc.15.79

• group and equatorial halogen) and ea (equatorial amine group and axial halogen) conformers (Figure 1) by dynamic NMR (DNMR) and theoretical calculations. Results and Discussion Experimental conformational population Low-temperature NMR experiments allow the identification of the individual conformers

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• -butoxide and DMF, to achieve high conversions to the target. A systematic study within our laboratory led to the identification of an iodide reagent which affords higher yields than previous approaches and allows for reactions to be conducted up to 10 g in scale under milder conditions. The use of a novel

• identification of a correlation between the methylene protons adjacent to the purine ring with C-5. A similar analysis by us revealed the same correlation, confirming 29 as the major product (Figure 4). While the amidine is itself an important moiety in medicinal chemistry [57], it can also be readily converted

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• identification, the authentic diazido compounds with known regiochemistry were synthesized using the appropriately spaced disulfonate capping agent, followed by azide opening of the cap and by chromatographic purification of the diazidated fractions [11][12] (reference reactions 1–3, Scheme 1). Direct

• allowed the identification of the spin system of each glucopyranose unit among which the tosylated ones can be identified using the resonance frequencies of H6,6’ as an entry point. Three staggered conformers with respect to the TsO–C(6)–C(5)–H(5) dihedral angle (see Figure 3d for numbering) are possible

• indicating (a) the anomeric proton (H1) region (5.20 to 4.70 ppm) and (b) the H6,6’-OTs proton region (4.30 to 3.90 ppm). (c) 2D TOCSY NMR spectrum of 6A,6D-ditosyl-β-CD: starting from each H1 resonance, identification of the signals that belong to the same spin system (dotted lines) is possible leading to

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

• Natural Science Foundation of China (Nos. 21672230, 81603022, 81125023), the SKLDR/SIMM Projects (SIMM 1705ZZ-01). We thank Prof. Xiu-Bao Li from Hainan University for the taxonomic identification of the soft coral material.

Back to the future: Why we need enzymology to build a synthetic metabolism of the future

• Tobias J. Erb

Beilstein J. Org. Chem. 2019, 15, 551–557, doi:10.3762/bjoc.15.49

• misannotated proteins, which is caused by automatized annotation algorithms that are often based on “simple” sequence similarities [43][44]. In selected enzyme (super)families the annotation error can be as high as 90% [45], which masks or even impedes the identification of novel functions within a given

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

• . Compounds 11 and 12 were separated during the isolation process and initially constructed to enable target identification. Compounds 11 and 12 might act as Michael acceptor (α,β-unsaturated carbonyl) and attach irreversibly and covalently to a potential target [23]. After purification and characterization

• , the azaindole derivatives are currently under investigation upon their use for fluorescence imaging. Furthermore, derivatives 3 and 6 will be further studied for identification of their actual target in S. aureus. This could be a serine protease that can also be addressed in the future by more stable

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• reactions can be integrated in the toolbox of chemical proteomics. Recently, following a similar strategy, Lu et al. reported on-DNA RCM and CM, an application potentially useful to generate DNA-encoded libraries for hit identification and target validation [90]. Substrates appended to oligonucleotides

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• ][11][12], it was only recently that NR+ and its phosphorylated form, nicotinamide mononucleotide (NMN), have become orally available as nutraceutical precursors of NAD+ [13][14][15][16]. This followed the identification of the biosynthetic pathways which use these ribosylated building blocks for the

Tandem copper and photoredox catalysis in photocatalytic alkene difunctionalization reactions

• Nicholas L. Reed,
• Madeline I. Herman,
• Vladimir P. Miltchev and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2019, 15, 351–356, doi:10.3762/bjoc.15.30

• ) complex. We describe herein the results of this investigation, which has led to the identification of a tandem photoredox copper(II) catalytic system for the net-oxidative difunctionalization of alkenes. Results and Discussion A range of mild oxidants can oxidize copper(I) to copper(II), and the use of

• the substrates [17], and that Cu(II) oxidants were uniquely suitable in this application. At the outset of this investigation, therefore, we imagined that the identification of a co-oxidant for use with catalytic Cu(II) might face similar practical constraints. Ideally, we hoped to identify a terminal

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• and characterization of four enantiomers 2 (Figure 3) came from the Japanese sources [45][46][47][48]. For identification purposes (2S*,3R*)-2 and (2S*,3S*)-2 were resolved by chiral reversed-phase TLC [26]. Kinetic resolution of dibenzyl (2S*,3R*)-N-Boc-3-hydroxyglutamate was achieved in the presence

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

• mediating and regulating numerous biological processes which are initiated by specific carbohydrate recognition. Much effort has been dedicated to the synthesis of specific lectin ligands in order to study and manipulate lectins. On the other hand, intensive work has been spent on the identification and

• macrophages and epithelial cells, the function of T4P has not yet been examined. Pili often have carbohydrate-binding activity. Whether mycobacterial pili are associated with lectin functions is, however, not known to date. Identification and characterization of the lectin mycotin and inhibition studies of

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• identification requires a good match of the recorded electron impact (EI) mass spectrum to a database spectrum and of the retention index, a standardised GC retention factor that is calculated from the retention times of the analytes and of n-alkanes [15], in comparison to an authentic standard or published data

• production of compounds from these classes aromatic compounds dominated, but the patterns were strain-specific. Identification of volatiles from Hypoxylon griseobrunneum A representative total ion chromatogram for the volatiles released by Hypoxylon griseobrunneum is shown in Figure 2 and the results of the

• structural assignment of 2,4,5-trimethylanisole for 24 was based on the better matching mass spectrum of this compound in comparison to the alternative of 24c. Compound 24 has not been reported from other natural sources before. The identification of 24 was further supported by a feeding experiment with

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

• derivatives; 2-aminobutyric acid; homoserine lactones; natural products; quorum sensing; Introduction The identification and structural elucidation of naturally occurring compounds traditionally requires isolation and NMR investigation as key method to detect novel compounds and new structural classes

• compounds proved to be either new NAMEs or constitute new classes of acylated amino acid methyl esters, derived from valine (NAVME), glycine (NAGME), or 2-aminobutyric acid (NABME). The identification of these compounds will be discussed based on the outlined approach including GC/MS analysis

• component within the broad peak. Mass spectra of natural compounds a) R (11, C16:1-NAGME) and b) S (10, C16:0-NAGME). EI mass spectrometric fragmentation of N-acylated amino acid derivatives. The ions w–z allow identification of the respective amino acid residue. MS2 spectra in ESI positive mode of a) Z9

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

• identification requires detailed structure elucidation, which in the end makes the design of an effective PPI modulator both difficult and challenging [19][20][21][22]. PPI modulation can be achieved through two opposite but complementary approaches: stabilization or inhibition (Figure 1). Although so far the

• efforts, mainly due to the development and implementation of more sophisticated screening methods and synthetic procedures, have led to the identification and clinical development of chemical entities that disrupt protein–protein interactions [15][25][26]. A selection of a few PPI modulators that have

• was screened by X-ray crystallography leading to the identification of four fragment hits. In an attempt to improve their binding affinities, another library was searched for compounds displaying similarity to these initial hits. After a docking-based screening followed by a fluorescence polarization

Enhanced single-isomer separation and pseudoenantiomer resolution of new primary rim heterobifunctionalized α-cyclodextrin derivatives

• Iveta Tichá,
• Gábor Benkovics,
• Milo Malanga and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2018, 14, 2829–2837, doi:10.3762/bjoc.14.261

• presence of pseudoenantiomers (AC/CA) as will be discussed further in the section on pseudoenantiomers identification. Pure AB, AC and AD regioisomers were isolated by reversed-phase column chromatography eluting with an ACN/H2O gradient. The AB 8b and AC 8c regioisomers were separated and obtained in the

• substituents (mesitylenesulfonyl and azido) are attached to the primary rim of α-CD. The incomplete anomeric doublets splitting prevented us from identifying the different regioisomeric peaks fully by NMR measurements. Pseudoenantiomers identification of heterodisubstituted α-CDs by HPLC–MS Furthermore, we

The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• Mycobacterium tuberculosis [9][10]. The emergence of MDR-TB has led to structure–activity studies to enhance the antitubercular activity of phenothiazines leading to the identification of chlorpromazine analogue 1 (Figure 1) which demonstrates MIC values comparable to first-line TB drugs in vitro [11]. However

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

• adhesion in mice [18][19]. These compounds have been extensively optimized in many works published by both groups, culminating in the identification of mannophosphates as prodrugs to increase oral bioavailability [20] and mannose C-glycosides, such as compound 6 , demonstrating enhanced in vivo metabolic