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

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• derivatives proved to be relatively easy to separate due to sufficiently different retention factors on TLC allowing their effective separation by column chromatography. All compounds exhibited characteristic signals in 1H NMR which facilitates their identification in the mixtures. The structure of products 6

A challenging redox neutral Cp*Co(III)-catalysed alkylation of acetanilides with 3-buten-2-one: synthesis and key insights into the mechanism through DFT calculations

• Andrew Kenny,
• Alba Pisarello,
• Arron Bird,
• Paula G. Chirila,
• Alex Hamilton and
• Christopher J. Whiteoak

Beilstein J. Org. Chem. 2018, 14, 2366–2374, doi:10.3762/bjoc.14.212

• energy difference between the C–H activation and C–C bond formation steps makes identification of the rate limiting step difficult by DFT calculations alone, however, parallel kinetic isotope effect (KIE) experiments do suggest that the C–H activation step is not rate limiting (KIE = 1.3), which is not

The enzymes of microbial nicotine metabolism

• Paul F. Fitzpatrick

Beilstein J. Org. Chem. 2018, 14, 2295–2307, doi:10.3762/bjoc.14.204

• kDa subunit with an FAD binding site, and an 87.7 kDa subunit containing the molybdopterin site, respectively [9][10]. Consistent with this identification, expression of the active enzyme required molybdopterin [9], and pAO1 contains a number of genes that have been identified as coding for proteins

• oxidase (MAO) family of flavoproteins (Figure 1) [16]. The reaction product was originally identified as arising from oxidation of the C2–C3 bond of the pyrrolidine ring [17]. Based on the structures and this product identification, a detailed mechanism was proposed in which initial oxidation of L-6

• been cloned and characterized [10]. DHPH contains FAD and requires NADH and oxygen [41], and the sequence of the protein is similar to that of salicylate hydroxylase, although the sequence identity is only 21%. This allowed identification of the enzyme as a flavin-dependent phenol hydroxylase, a

Determining the predominant tautomeric structure of iodine-based group-transfer reagents by ¹⁷O NMR spectroscopy

• Nico Santschi,
• Cody Ross Pitts,
• Benson J. Jelier and
• René Verel

Beilstein J. Org. Chem. 2018, 14, 2289–2294, doi:10.3762/bjoc.14.203

• ). Given that the larger the difference ∆δiso, the more likely a successful structural assignment based on 17O NMR spectroscopy becomes, this technique may indeed prove useful for the identification of the isomeric pairs 2–6. Accordingly, spectral data on 1, 2a, 3a, 4a, 5 (assuming no assignment ), and 6

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

• complex chemistry. We have shortlisted the papers which contained different equipment’s used in the pharmaceutical manufacturing to cover most of the functional groups which can be organized on the single platform and can be utilized for a number of chemical syntheses. After identification of specific

The phenyl vinyl ether–methanol complex: a model system for quantum chemistry benchmarking

• Dominic Bernhard,
• Fabian Dietrich,
• Mariyam Fatima,
• Cristóbal Pérez,
• Hannes C. Gottschalk,
• Axel Wuttke,
• Ricardo A. Mata,
• Martin A. Suhm,
• Melanie Schnell and
• Markus Gerhards

Beilstein J. Org. Chem. 2018, 14, 1642–1654, doi:10.3762/bjoc.14.140

• dispersion interactions [48]. The aim of the presented study is the unambiguous experimental identification of the preferred binding site of a first methanol solvent molecule to the multivalent hydrogen bond scaffold of phenyl vinyl ether, followed by a classification of theoretical methods in terms of

• also indicated in the FTIR and the IR–UV investigations, which are, however, unable to distinguish OH–O from OH–O’) and the OH–P isomer, respectively. The identification of the two complexes to the OH–O’ and the OH–P isomers is guided by the absolute and relative values of the B and C rotational

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• , we have steadily pursued the identification of novel antitumor and antiviral nucleoside derivatives [17][20][21][22]. Matsuda and co-workers reported a 2’-substituted cytidine derivative, DMDC (1), with potent antitumor activity [23][24]. In other reports, Walker [25] and Secrist [26] independently

• towards oligosaccharides, which would also contribute to the identification and development of drug candidates. For example, cancer immunotherapy based on vaccines derived from carbohydrate antigen–adjuvant combinations has received much attention in recent years [75][76][77]. However, the difficulties

• greatly improved the efficiency of the synthesis of nucleosides and oligosaccharides. The results of these syntheses demonstrate the power of glycoside bond-forming reactions, and should assist in the future identification or synthesis of biologically active nucleoside and glycoconjugate derivatives

Spectroelectrochemical studies on the effect of cations in the alkaline glycerol oxidation reaction over carbon nanotube-supported Pd nanoparticles

• Dennis Hiltrop,
• Steffen Cychy,
• Karina Elumeeva,
• Wolfgang Schuhmann and
• Martin Muhler

Beilstein J. Org. Chem. 2018, 14, 1428–1435, doi:10.3762/bjoc.14.120

• substantial local pH drop and cannot be fully compensated by OH− diffusion from the bulk into the thin layer. This pH drop further complicates the identification of products, because the product selectivity may change as a function of pH as demonstrated by Wang et al. [13] on a Pd disk electrode for ethylene

• /C, PdAg/C [23] and PtBi/C [21] in alkaline medium using IR spectroscopy for product identification. Strmcnik et al. [24] investigated the effect of different alkali ions using LiOH, NaOH, KOH and CsOH on the observed currents in the hydrogen oxidation, oxygen reduction and methanol oxidation

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• [2][3]. Their high cytotoxicity prompted manifold studies that were initially focussed on the total synthesis and structure–activity relationships [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. This work resulted in the identification of cryptophycin-52, a highly biologically active

Volatiles from three genome sequenced fungi from the genus Aspergillus

• Jeroen S. Dickschat,
• Ersin Celik and
• Nelson L. Brock

Beilstein J. Org. Chem. 2018, 14, 900–910, doi:10.3762/bjoc.14.77

• unambiguous identification. Compound 30 was previously tentatively identified from Nodulisporium [47], while the other esters of this series 31, 33, 34, 39, and 40 have not been reported from fungi before. Conclusion In summary, the volatiles from three species of the genus Aspergillus were identified. A

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• reported on the identification of a novel daunorubicin–GnRH-III conjugate (GnRH-III–[4Lys(Bu), 8Lys(Dau=Aoa)] with efficient in vitro and in vivo antitumor activity. To get a deeper insight into the mechanism of action of our lead compound, the cellular uptake was followed by confocal laser scanning

Volatiles from the xylarialean fungus Hypoxylon invadens

• Jeroen S. Dickschat,
• Tao Wang and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 734–746, doi:10.3762/bjoc.14.62

• –MS analysis of the obtained extracts [8]. Compound identification is then usually performed by comparison of measured mass spectra to mass spectra in electronic libraries, in addition to comparison of measured to published retention indices. Positive compound identification can be assumed, if the

• α-cadinene (5). The same problem applies to the unambiguous identification of regioisomers of aromatic compounds. We have recently reported on the GC–MS-based identification of the fungal volatiles 1-chloro-3,4-dimethoxybenzene (6) and 1,3-dichloro-4,5-dimethoxybenzene (7) from an endophytic

• Geniculosporium sp. by comparison of the natural products to all possible regioisomers that were obtained by chemical synthesis [9]. Here we report on the identification of the volatiles emitted by the xylarialean fungus Hypoxylon invadens MUCL 54175, a highly interesting pyrenomycete that was recently described

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• 3:7). Removal of the chiral auxiliary. Synthesis of isoindolinones 1a–c, 1e, 2; isolated yield, ee by HPLC. Synthesis of pazinaclone analogue (3S)-27. Identification of the optimum reaction conditions for the diastereoselective intramolecular aza-Michael reaction of (S)-6a. Identification of the

An alternative to hydrogenation processes. Electrocatalytic hydrogenation of benzophenone

• Cristina Mozo Mulero,
• Alfonso Sáez,
• Jesús Iniesta and
• Vicente Montiel

Beilstein J. Org. Chem. 2018, 14, 537–546, doi:10.3762/bjoc.14.40

• hydrogenation process instead of diatomic hydrogen formation as competitive and side reaction by considering a slow PdHad formation rate of this. HPLC analysis was performed for the identification and quantification of the benzophenone depletion and final product formation from the electrocatalytic

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• selection and identification of mutants with improved properties is a favoured method in the field of white biotechnology and biocatalysis, to improve the fitness of enzymes for industrial application [5]. In general, directed evolution may be summarized as an iterative two-step process which involves the

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• evaluation. Here, we present the identification, synthesis and bioactivities of volatiles emitted by the rare tropical hypoxylaceous ascomycete Daldinia clavata, which has hitherto been only infrequently reported from Africa and Latin America. Results and Discussion Headspace analysis The volatiles emitted

• by agar plate cultures of Daldinia clavata MUCL 47436 grown on YMG medium were collected on charcoal filter traps by application of a closed-loop stripping apparatus (CLSA) [17]. Dichloromethane extracts of the charged filters were analysed by GC–EIMS, followed by identification of the captured

• to an authentic standard and to synthetic standards of all possible positional isomers. These isomers have been made accessible during our previous work that resulted in the identification of 1,5-dichloro-2,3-dimethoxybenzene as a headspace constituent of an endophytic Geniculosporium sp. [35]. The

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• been reported so far. Further, this literature search showed that two total syntheses of isoquinoline 1 had been published even before its identification as a natural product (Figure 1). In 1963, Franck and Blaschke [11] obtained 1 by dehydrogenation of its 1,2,3,4-tetrahydro analogue (which itself had