Isotopically labeled sulfur compounds and synthetic selenium and tellurium analogues to study sulfur metabolism in marine bacteria

• Nelson L. Brock,
• Christian A. Citron,
• Claudia Zell,
• Martine Berger,
• Irene Wagner-Döbler,
• Jörn Petersen,
• Thorsten Brinkhoff,
• Meinhard Simon and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 942–950, doi:10.3762/bjoc.9.108

• sulfur source for the MeSH volatiles, whereas incorporation of labeling from sulfate was not observed. Moreover, the utilization of selenite and selenate salts by marine alphaproteobacteria for the production of methylated selenium volatiles was explored and resulted in the production of numerous

• strain of DSS-3. The incorporation rates of the deuterium labeling into the MeSH-derived volatiles were reduced (64% for 1) in comparison to the wild type strain (95%) and the ratio of the cleavage pathway increased to 35% (Figure 4B). The incorporation of isotopic labeling from [2H6]DMSP by the dmdA

• GC–MS. No incorporation of the 34S-labeling from sulfate or thiosulfate into the MeSH-derived volatiles was observed, pointing strongly away from a significant involvement of sulfate reduction in the biosynthesis of MeSH. Instead, feeding of [methyl-2H3]methionine led to an effective incorporation of

End-labeled amino terminated monotelechelic glycopolymers generated by ROMP and Cu(I)-catalyzed azide–alkyne cycloaddition

• Ronald Okoth and
• Amit Basu

Beilstein J. Org. Chem. 2013, 9, 608–612, doi:10.3762/bjoc.9.66

• from the NHS ester of pyrene butyric acid 13 via intermediate 14, afforded the pyrene-end-labeled glycopolymers 16. The extent of pyrene labeling was determined by UV–vis spectroscopy and found to be essentially quantitative for the galactosyl and mannosyl polymers. The SGal polymer 12c only underwent

• 60% labeling under these conditions. In conclusion we have presented here a facile method for accessing monotelechelic ROMP polymers and demonstrated that subsequent post-polymerization modifications can be assessed accurately by a general method such as 1H NMR. This method allows access to well

Caryolene-forming carbocation rearrangements

• Quynh Nhu N. Nguyen and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2013, 9, 323–331, doi:10.3762/bjoc.9.37

• positioned on opposite sides of the hydrocarbon substrate due to the steric congestion at its core (note the position of NH3 throughout Figure 7), a scenario that could be probed by deuterium labeling of farnesyl diphosphate if a suitable caryolene synthase were isolated. The energetics for both pathways

A new synthetic protocol for coumarin amino acid

• Xinyi Xu,
• Xiaosong Hu and
• Jiangyun Wang

Beilstein J. Org. Chem. 2013, 9, 254–259, doi:10.3762/bjoc.9.30

• the application of fluorescent labeling of living cells. Compared with GFP, compound 1a is small, and can be incorporated at any defined site in proteins; whereas GFP is large, which will cause significant perturbation, and can only be fused to the C- or N-terminus of the target protein [9]. The

• cannot be achieved by using GFP labeling technique since GFP is relatively insensitive to the pH and the solvent polarity of the solution. Many more examples of the usage of 1a have also been reported [5][6][7][8]. Due to the high importance of 1a, there has been a great need for a highly efficient and

• , by using the Henderson–Hasselbalch equation. The halogenation of 1a at the 6-position decreases the pKa value, which makes compounds 1b and 1c good substitutes for 1a in fluorescent labeling and other investigations in biological systems. Screening for the synthetase/tRNA pair for 1b and 1c is under

Radical zinc-atom-transfer-based carbozincation of haloalkynes with dialkylzincs

• Fabrice Chemla,
• Florian Dulong,
• Franck Ferreira and
• Alejandro Pérez-Luna

Beilstein J. Org. Chem. 2013, 9, 236–245, doi:10.3762/bjoc.9.28

• warming, the zinc carbenoid is stereochemically labile and isomerizes to its more stable form. In the absence of added air, no decomposition of the carbenoid intermediate is observed at room temperature for at least 24 h. Deuterium labeling and iodolysis experiments evidence that the zinc carbenoids

Development of peptidomimetic ligands of Pro-Leu-Gly-NH₂ as allosteric modulators of the dopamine D₂ receptor

• Swapna Bhagwanth,
• Ram K. Mishra and
• Rodney L. Johnson

Beilstein J. Org. Chem. 2013, 9, 204–214, doi:10.3762/bjoc.9.24

• /bjoc.9.24 Abstract A variety of stable, small-molecule peptidomimetic ligands have been developed to elucidate the mechanism by which the neuropeptide Pro-Leu-Gly-NH2 (PLG) modulates dopaminergic neurotransmission. Photoaffinity labeling ligands based upon PLG peptidomimetics have been used to

• receptor agonists to dopamine receptors [7], and to prevent neuroleptic drug-induced supersensitivity of post-synaptic dopamine receptors [8]. The molecular basis behind this enhancement of dopaminergic neurotransmission did not become known until several decades later when photoaffinity-labeling

An improved synthesis of a fluorophosphonate–polyethylene glycol–biotin probe and its use against competitive substrates

• Hao Xu,
• Hairat Sabit,
• Gordon L. Amidon and
• H. D. Hollis Showalter

Beilstein J. Org. Chem. 2013, 9, 89–96, doi:10.3762/bjoc.9.12

• last one. FP probes have been used mostly in the development of covalent inhibitors for pharmacologically interesting serine hydrolases due to their strong binding and rapid labeling properties. We have shown that for serine hydrolases with reversible substrates, FP probes can also be useful tools if

• ), 1.42–1.33 (m, 8H); MS m/z: 329.1 [M + H]+. Structure of FP–PEG–biotin 1. Labeling and affinity isolation of serine hydrolases by FP–PEG–biotin 1. (A) Lane 1: Protein standard. Lane 2: Mixture of BSA, pCES, NP, trypsin before purification. Lane 3: Purification results. (B) Rat tissue homogenates were

Chemical–biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target

• Jonathan W. Choy,
• Clifford Bryant,
• Claudia M. Calvet,
• Patricia S. Doyle,
• Shamila S. Gunatilleke,
• Siegfried S. F. Leung,
• Kenny K. H. Ang,
• Steven Chen,
• Jiri Gut,
• Juan A. Oses-Prieto,
• Jonathan B. Johnston,
• Michelle R. Arkin,
• Alma L. Burlingame,
• Jack Taunton,
• Matthew P. Jacobson,
• James M. McKerrow,
• Larissa M. Podust and
• Adam R. Renslo

Beilstein J. Org. Chem. 2013, 9, 15–25, doi:10.3762/bjoc.9.3

• due to lower abundance and labeling below the limit of fluorescence detection. The discovery of a potential mammalian off-target of probe 9 (and presumably also of 1) was of considerable interest, so we explored this finding further. To determine if this protein was also a target of 1 and 4, we

• . In these experiments, pretreatment with 10 μM of compound 1, 3, or 4 successfully blocked labeling of the ≈35 kDa band by probe 9, thus indicating that these compounds also react with this target (Figure 6). As expected, the nonelectrophilic dihydro forms of 1 and 4 (i.e., compounds 6 and 8) did not

• compete for labeling by 9. Taken together, these results strongly suggest that compounds 1, 3 and 4 react irreversibly with the ≈35 kDa protein in a process involving the electrophilic vinylsulfone moiety. Chemical proteomics We next applied mass spectrometric analysis to identify the ≈35 kDa band, which

Hydrophobic analogues of rhodamine B and rhodamine 101: potent fluorescent probes of mitochondria in living C. elegans

• Laurie F. Mottram,
• Safiyyah Forbes,
• Brian D. Ackley and
• Blake R. Peterson

Beilstein J. Org. Chem. 2012, 8, 2156–2165, doi:10.3762/bjoc.8.243

• tissues by confocal laser scanning microscopy after treatment for 2 h at concentrations as low as 100 picomolar. Because transgenes are poorly expressed in the germline of these animals, these small molecules represent superior tools for labeling dynamic mitochondria in this tissue compared with the

• substantial aqueous solubility, which is beneficial for some applications, such as protein labeling, but also results in low cellular permeability in assays involving living cells. Hydrophobic analogues of fluorescein such as Tokyo Green (2) [2], Pennsylvania Green (3) [3][4], and others [5] have been

• . Labeling of specific organelles by rhodamine 6G (7), HRB 9, and HR101 10 was observed in hypodermis, muscle, neurons (data not shown), and the germline of these animals (Figure 5). Examination of the pattern of staining in the germline, part of the distal gonad containing a population of germ cells that

Dimerization of a cell-penetrating peptide leads to enhanced cellular uptake and drug delivery

• Jan Hoyer,
• Ulrich Schatzschneider,
• Michaela Schulz-Siegmund and
• Ines Neundorf

Beilstein J. Org. Chem. 2012, 8, 1788–1797, doi:10.3762/bjoc.8.204

• introduction of N-terminal modifications. To test the hypothesis of improved internalization behavior of the dimer, we conducted flow-cytometric cellular uptake studies with sC18 versus (sC18)2 in various cell lines after N-terminal labeling with carboxyfluorescein (labeling of the dimer occurred at the N

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• cells were reached when cells were grown for 48 h before radioactive labeling. In general, more cells adhered to fibronectin than to fibrinogen. WM-266-4 cells derived from the metastasis show a completely different growth and adhesion behavior compared to the cells isolated from the primary melanoma

Identification and isolation of insecticidal oxazoles from Pseudomonas spp.

• Florian Grundmann,
• Veronika Dill,
• Andrea Dowling,
• Aunchalee Thanwisai,
• Edna Bode,
• Narisara Chantratita,
• Richard ffrench-Constant and
• Helge B. Bode

Beilstein J. Org. Chem. 2012, 8, 749–752, doi:10.3762/bjoc.8.85

• A and B. Labeling experiments confirmed their structures and gave initial evidence for a novel biosynthesis pathway of these natural oxazoles. In order to confirm their structure, they were synthesized, which also allowed tests of their bioactivity. Additionally, the bioactivities of the synthesis

• characteristic fragment ion of 130 m/z [M + H]+ (Supporting Information File 1, Figure S2), and labeling experiments (Supporting Information File 1, Figure S3) enabled the elucidation of this ion as 3-methylidene-3H-indolium (Figure 1). In order to determine the genus of the producing strain PB22.5, we sequenced

• produces compounds 3–6 but not 1 and 2. Furthermore two novel oxazole derivatives named labradorin 3 (7, 268.4 m/z [M + H]+, C17H20N2O) and labradorin 4 (8, 283.2 m/z [M + H]+, C18H22N2O) were detected, but they could not be isolated due to their very low production. Labeling experiments were performed in

Synthesis of fluorinated maltose derivatives for monitoring protein interaction by ¹⁹F NMR

• Michaela Braitsch,
• Hanspeter Kählig,
• Georg Kontaxis,
• Michael Fischer,
• Toshinari Kawada,
• Robert Konrat and
• Walther Schmid

Beilstein J. Org. Chem. 2012, 8, 448–455, doi:10.3762/bjoc.8.51

• be probed by following the NMR relaxation changes of the ligand (e.g., selective T1 or T2, which reflect the effective molecular weight). Due to this indirect detection scheme no isotope labeling of the protein interaction partners is required and consumption of protein material is reduced. The

• in the binding pocket of the complex between MBP and maltose (PDB ID code 1ANF); hydrogen bonds are shown as dashed lines. 2-19F-Maltose reporter system: Nonstereoselective fluorine labeling at the 2-position of maltose leads to a 2/1 mixture of two epimeric forms [left: gluco-type; right: manno-type

Synthesis of highly functionalized β-aminocyclopentanecarboxylate stereoisomers by reductive ring opening reaction of isoxazolines

• Melinda Nonn,
• Loránd Kiss,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2012, 8, 100–106, doi:10.3762/bjoc.8.10

• labeling scheme. The thermal ellipsoids are drawn at the 20% probability level. Isoxazoline-fused β-aminocyclopentanecarboxylate regio- and stereoisomers [8]. Treatment of isoxazoline-fused amino ester 2 with NaBH4. Reduction with Pd/C in the presence of HCO2NH4. Transformation of isoxazoline-fused

Continuous flow photolysis of aryl azides: Preparation of 3H-azepinones

• Farhan R. Bou-Hamdan,
• François Lévesque,
• Alexander G. O'Brien and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2011, 7, 1124–1129, doi:10.3762/bjoc.7.129

• tools, both for preparative heterocycle synthesis [16][17] and for photoaffinity labeling of proteins [18][19][20]. The photolysis of aryl azide 1 [21], a well-studied and widely used reaction [22][23][24][25][26][27][28][29][30], generates the singlet aryl nitrene intermediate 12 (Scheme 1). Ring

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• sp3-hybridized C–H bond can be achieved by undergoing 1,3-addition to a vinyl–carbenoid intermediate [142]. The bicyclo[3.2.1]oct-6-en-2-ones 265 and 267 could be synthesized stereoselectively by this method. Deuterium labeling experiments indicated the cyclization involved an unprecedented 1,3

• via oxidative gold catalysis and provided expedient access to various substituted N- or O-heterocycles (344–351) (Scheme 57). Deuterium labeling experiments were carried out to unveil the reaction mechanism. The results established the anti nature of the alkene functionalization and the indispensable

When gold can do what iodine cannot do: A critical comparison

• Sara Hummel and
• Stefan F. Kirsch

Beilstein J. Org. Chem. 2011, 7, 847–859, doi:10.3762/bjoc.7.97

• selectivity and 90% yield (Scheme 9a) [91]. Labeling experiments showed that the proposed mechanism where the cation is trapped by the nucleophile and subsequent loss of the proton and protodemetallation is viable. A more elaborate study of 5-endo hydroxy- and alkoxycyclizations of 1,5-enynes was described by

Gold-catalyzed heterocyclizations in alkynyl- and allenyl-β-lactams

• Benito Alcaide and
• Pedro Almendros

Beilstein J. Org. Chem. 2011, 7, 622–630, doi:10.3762/bjoc.7.73

• reveal, 5-exo oxyauration via 16 is restricted by the steric hindrance between the (methoxymethyl)oxy group and the substituents at the quaternary stereocenter. With the aim of trapping the organo–gold intermediate to confirm the mechanism of this reaction, deuterium labeling studies with deuterium oxide

Construction of cyclic enones via gold-catalyzed oxygen transfer reactions

• Leping Liu,
• Bo Xu and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2011, 7, 606–614, doi:10.3762/bjoc.7.71

• labeling experiment was designed to elucidate the pathway responsible for the gold-catalyzed intramolecular oxygen transfer of 2-alkynyl-1,5-diketones (Scheme 8). By introducing an 18O atom into one of the carbonyls of the substrate, and using the 13C NMR spectra of the substrate and product to locate the

• cyclization of alkynyl ketones. Gold-catalyzed cyclization of terminal alkynyl ketones. Gold-catalyzed tandem oxygen transfer/Nazarov cyclizations. TfOH-mediated cyclization of alkynyl ketones. Gold-catalyzed cyclizations of 2-alkynyl-1,5-diketones. Designed isotopic labeling experiment for mechanistic

• cyclization of internal diynes. Proposed solvolysis/cyclization mechanism. Gold-catalyzed cyclization of alkynyl epoxides and the 18O isotopic labeling experiment. Proposed oxygen transfer mechanism. Gold or silver-catalyzed cyclization of alkynyl epoxides and the corresponding deuterium labeling experiment.

Unusual behavior in the reactivity of 5-substituted-1H-tetrazoles in a resistively heated microreactor

• Bernhard Gutmann,
• Toma N. Glasnov,
• Tahseen Razzaq,
• Walter Goessler,
• Dominique M. Roberge and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2011, 7, 503–517, doi:10.3762/bjoc.7.59

• from the resulting azido group and a subsequent 1,2-migration of the acylimido group from carbon to nitrogen to give the same nitrilimine intermediate was ruled out by Herbst via 15N labeling studies [44]. The degradative acylation of 5-substituted-1H-tetrazoles with acyl halides is in fact an elegant

En route to photoaffinity labeling of the bacterial lectin FimH

• Thisbe K. Lindhorst,
• Michaela Märten,
• Andreas Fuchs and
• Stefan D. Knight

Beilstein J. Org. Chem. 2010, 6, 810–822, doi:10.3762/bjoc.6.91

• FimH that can complex α-D-mannosides. However, as the precise nature of the ligand–receptor interactions in mannose-specific adhesion is not yet fully understood, it is of interest to identify carbohydrate recognition domains on the fimbrial lectin also in solution. Photoaffinity labeling serves as an

• appropriate methodology in this endeavour and hence biotin-labeled photoactive mannosides were designed and synthesized for photoaffinity labeling of FimH. So far, the photo-crosslinking properties of the new photoactive mannosides could be detailed with the peptide angiotensin II and labeling of FimH was

• shown both by MS/MS studies and by affino dot–blot analysis. Keywords: diazirines; FimH; lectins; MS/MS analysis; photoactive mannoside ligands; photoaffinity labeling; Introduction Photoaffinity labeling is a technique by which ligand binding sites of a receptor protein can be identified in solution

Novel tetracyclic structures from the synthesis of thiolactone-isatin hybrids

• Renate Hazel Hans,
• Hong Su and
• Kelly Chibale

Beilstein J. Org. Chem. 2010, 6, No. 78, doi:10.3762/bjoc.6.78

• from MeOH at room temperature and subjected to crystallographic analysis (see Supporting Information File 2 for crystallographic data). Figure 3 shows the molecular structure and atom labeling for 4a. The crystals are triclinic with space group P−1 and contains four molecules per unit cell. The crystal

• repulsive steric interaction between the relatively bulky hydroxyl group at C7A and the adjacent methyl group at C5A. Figure 4 shows the molecular structure atom labeling for 4b–c. Both compounds crystallized in the centrosymmetric monoclinic space group P21/n with 4 molecules in the unit cell. Similar to

Synthetic incorporation of Nile Blue into DNA using 2′-deoxyriboside substitutes: Representative comparison of (R)- and (S)-aminopropanediol as an acyclic linker

• Daniel Lachmann,
• Sina Berndl,
• Otto S. Wolfbeis and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2010, 6, No. 13, doi:10.3762/bjoc.6.13

• ” ligation strategy has become an important strategy for postsynthetic labeling of DNA [12][13]. Huisgen described first the [2+3]-cycloaddition between alkynes and azides yielding 1,2,3-triazoles [14]. The utility of this reaction as a bioligation method has grown incredibly after Meldal [15] and – almost

Recognition properties of receptors consisting of imidazole and indole recognition units towards carbohydrates

• Monika Mazik and
• André Hartmann

Beilstein J. Org. Chem. 2010, 6, No. 9, doi:10.3762/bjoc.6.9

• signal (for labeling, see Figure 2), downfield shift and strong broadening of the NHD signal as well as changes of the chemical shifts of the CH3F,G, CH2B,C,E, pyridine CH and imidazole or indole CH resonances of 4 or 5 (see Table 2). The signal due to the indole NH of 5 shifted downfield by 0.20–0.40

Synthesis of coumarin or ferrocene labeled nucleosides via Staudinger ligation

• Ivana Kosiova,
• Andrea Janicova and
• Pavol Kois

Beilstein J. Org. Chem. 2006, 2, No. 23, doi:10.1186/1860-5397-2-23

• gives iminophosphoranes which can react with almost any kind of electrophilic reagent, e.g. aldehydes/ketones to form imines or esters to form amides. This so-called Staudinger ligation has been employed in a wide range of applications as a general tool for bioconjugation including specific labeling of

• , [22][23] including specific labeling of nucleic acids, [24] proteomic studies [25][26] and modification of cell surfaces. [17][18] We applied the Staudinger ligation for nucleoside labeling procedures, using coumarin and ferrocene derivatives as labels. According to our knowledge, applications of this

• with maxima of 1a-c. We observed only slight changes of fluorescence intensity in the series of coumarin labeled nucleosides. We also tested the Staudinger ligation as a prospective method for the electrochemical labeling of nucleosides and nucleotides with ferrocene derivatives. 2'-Azido-2