The EIMS fragmentation mechanisms of the sesquiterpenes corvol ethers A and B, epi-cubebol and isodauc-8-en-11-ol

• Patrick Rabe and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1380–1394, doi:10.3762/bjoc.12.132

• EIMS fragmentation mechanisms of the two sesquiterpene ethers corvol ethers A and B, and the sesquiterpene alcohols epi-cubebol and isodauc-8-en-11-ol. Keywords: bacteria; isotopic labelling; mass spectrometry; reaction mechanisms; terpenes; Introduction Gas chromatography coupled to electron impact

• , introduction of labelling into the various positions of the compound of interest may require a different synthetic strategy for each individual target isotopomer. Most of these studies made use of deuterium labellings that can frequently be introduced into reactive positions of a (functionalised) terpene

• isolated from the producing organism. Deuterium labellings also allow to follow hydrogen rearrangements, but non-specific hydrogen migrations during the fragmentation process and kinetic isotope effects can make data interpretation difficult. In contrast, the introduction of 13C-labelling into a terpene

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• and its target dsDNA sequence fragment used in our previous work are shown on Figure 5. In addition to the terminal alkyne group, an amine group was introduced into the α-position of the γ-aminobutyric acid linker (Figure 5B). This provides versatility for labelling of MGBs. For example, the terminal

• alkyne can be used for labelling of MGB with a fluorophore using "click chemistry" and the amino group can be used to conjugate the probe to TFO or to another polyamide [15] and vice versa. Synthesis of modified polyamides, containing an azide or alkyne group The following polyamides (11–14, Figure 6

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• phosphate. This points to an adenylation-type mechanism, and the authors also proposed a hemiorthoamide mechanism to account for the absence of wasted ATP hydrolysis (Figure 3B, pathway a). An alternative mechanism that would also account for the [18O]-labelling results involves direct activation of the

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• : deuterium labelling; nanomedicine; Raman spectroscopy; Shapiro reaction; squalene; Introduction Application of nanotechnology to medicine holds promises to profoundly impact healthcare especially to treat severe diseases such as cancer, intracellular infections, neurodegenerative diseases, etc. Indeed, the

Natural products in synthesis and biosynthesis II

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 413–414, doi:10.3762/bjoc.12.44

• methods such as isotopic labelling experiments [8] continue to be important. I thank all contributors that participated in this third Thematic Series on natural product chemistry in the Beilstein Journal of Organic Chemistry and also the whole team at the Beilstein-Institut for their professional work. I

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• -assisted click cluster synthesis. An example of the MW-promoted ‘cooperative’ click reaction of azido-CDs has recently been reported and offers useful synthetic insights into a specific labelling strategy [54]. The aforementioned reaction afforded a new series of antimicrobial γ-CD derivatives that

Tandem processes promoted by a hydrogen shift in 6-arylfulvenes bearing acetalic units at ortho position: a combined experimental and computational study

• Mateo Alajarin,
• Marta Marin-Luna,
• Pilar Sanchez-Andrada and
• Angel Vidal

Beilstein J. Org. Chem. 2016, 12, 260–270, doi:10.3762/bjoc.12.28

• are conceivable for explaining these conversions. Deuterium labelling experiments exclude the [1,4]-hydride shift as the first step. A computational study scrutinized the reaction channels of these tandem conversions starting by [1,5]-, [1,7]- and [1,9]-H shifts, revealing that this first step is the

• from those starting by [1,5]-, [1,7]- or [1,9]-H shifts, represented in Scheme 4, by deuterium labelling experiments. Thus, if the conversion of the deuterated acetal-fulvene 14, in which deuterium replaces the proton at the acetalic carbon of 3a, was actually initiated by a [1,4]-deuteride shift, the

• (Scheme 6). 1H NMR analyses showed that only protons, not deuteriums, were linked to the C4 atom of 18 and to C9 of 19. Instead, one deuterium atom is found at the methylene group of each regioisomer. Moreover, we carried out a second labelling experiment by using now as starting material the

Conformational equilibrium in supramolecular chemistry: Dibutyltriuret case

• Karina Mroczyńska,
• Małgorzata Kaczorowska,
• Erkki Kolehmainen,
• Ireneusz Grubecki,
• Marek Pietrzak and
• Borys Ośmiałowski

Beilstein J. Org. Chem. 2015, 11, 2105–2116, doi:10.3762/bjoc.11.227

• , CDCl3) for complex of 1 with substituted benzoates. The signal labelling for [1]:[5] in 1:1 ratio exemplified on the spectra recorded at −40 °C (CDCl3) and structure of complexes. The variable temperature (+20 to −40 °C, CDCl3) dependence of the main signals (the highest integral values) in 1d∙∙∙5

The simple production of nonsymmetric quaterpyridines through Kröhnke pyridine synthesis

• Isabelle Sasaki,
• Jean-Claude Daran and
• Gérard Commenges

Beilstein J. Org. Chem. 2015, 11, 1781–1785, doi:10.3762/bjoc.11.193

• modifying the chelating properties of the polydentate ligands. Molecular view of compound 8 with the atom labelling scheme. Ellipsoids are drawn at the 50% probability level. H atoms are represented as small circles of arbitrary radii. Molecular view of compound 9 using the atom labelling scheme. Selected

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• transfer of an electron to the TiO2 will compete with the loss of CO2, thus reducing yields. An intriguing aspect of the process is the source of the H atoms gained during the formation of adducts 22 and 29. This was not the proton lost from the aromatic ring in forming 31. Deuterium labelling experiments

Articulated rods – a novel class of molecular rods based on oligospiroketals (OSK)

• Pablo Wessig,
• Roswitha Merkel and
• Peter Müller

Beilstein J. Org. Chem. 2015, 11, 74–84, doi:10.3762/bjoc.11.11

• carboxylates affords compounds 33a–c in moderate to good yields, whereas the reaction with NaN3 provided the ω,ω’-diazide 34. The latter compound served as interface for labelling with various alkyne-functionalized compounds. As proof-of-concept we successfully coupled 34 with the perylene derivative 35 to

Inclusion of trans-resveratrol in methylated cyclodextrins: synthesis and solid-state structures

• Lee Trollope,
• Dyanne L. Cruickshank,
• Terence Noonan,
• Susan A. Bourne,
• Milena Sorrenti,
• Laura Catenacci and
• Mino R. Caira

Beilstein J. Org. Chem. 2014, 10, 3136–3151, doi:10.3762/bjoc.10.331

• -independent complex units of TMA·RSV·6.25H2O (A and B), with only the major component of disorder shown for RSV in host B (a), and the non-H atom and methylglucose ring nomenclature illustrated for host A as representative (b). For clarity, host H atoms have been omitted. Representative atomic labelling for

Synthesis of nanodiamond derivatives carrying amino functions and quantification by a modified Kaiser test

• Gerald Jarre,
• Steffen Heyer,
• Elisabeth Memmel,
• Thomas Meinhardt and
• Anke Krueger

Beilstein J. Org. Chem. 2014, 10, 2729–2737, doi:10.3762/bjoc.10.288

• functional moiety is not prone to hydrolytic or enzymatic decay. Stable conjugation is an essential prerequisite for applications such as labelling or targeting. Here we report on the grafting of nitrogen-containing heterocyclic aromatic compounds using the Diels–Alder reaction of suitable starting materials

Superoxide chemistry revisited: synthesis of tetrachloro-substituted methylenenortricyclenes

• Basavaraj M. Budanur and
• Faiz Ahmed Khan

Beilstein J. Org. Chem. 2014, 10, 2531–2538, doi:10.3762/bjoc.10.264

• did not yield any product which suggested that there is a unique and exceptional degree of reactivity of the superoxide ion species which triggered this kind of reaction. To elucidate the reaction mechanism, we have performed a deuterium labelling experiment by treating 3c with KO2 in DMSO-d6 at rt

• reaction was derived through a controlled experiment with BHT which improved the yields of nortricyclenes and a deuterium labelling experiment using DMSO-d6. Further, acylation reactions of the synthesized methylenenortricyclens afforded the 2-propanone-substituted pentachloronorbornenes in good yields

Specific DNA duplex formation at an artificial lipid bilayer: fluorescence microscopy after Sybr Green I staining

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2014, 10, 2307–2321, doi:10.3762/bjoc.10.240

• left) during filling the syringes with buffer. C) Labelling of the single compartments and ports of the ‘Bilayer Slide’. These are disposable, optically transparent microfluidic sample carriers with perfusion capabilities. D) Schematic demonstration of the cis chamber perfusion. E) Shot of the device

Supercritical carbon dioxide: a solvent like no other

• Jocelyn Peach and
• Julian Eastoe

Beilstein J. Org. Chem. 2014, 10, 1878–1895, doi:10.3762/bjoc.10.196

• to contrast individual components in a multicomponent mixture through selective isotropic (hydrogen/deuterium) labelling. Research around a group of tri-chain surfactants has been carried out through the addition of a third extensively methylated tail in hope to both enhance CO2 compatibility and to

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• -substituted-3-aminooxindole core. ORTEP [37] view of one of the two independent molecules of 4a present in the asymmetric unit, showing the arbitrary atom-labelling scheme. Atomic displacement parameters for non-H atoms are at a probability level of 50%. Proposed explanation of the stereochemical outcome of

Molecular recognition of isomeric protonated amino acid esters monitored by ESI-mass spectrometry

• Andrea Liesenfeld and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 825–831, doi:10.3762/bjoc.10.78

• that has to be taken into account: non-covalent isotope effects [23] might also cause significant differences of the signals’ intensities. Therefore, every experiment has to be repeated with the different order of isotope labelling and in addition one should measure the same isomer in both forms – non

Self-assembly of metallosupramolecular rhombi from chiral concave 9,9’-spirobifluorene-derived bis(pyridine) ligands

• Rainer Hovorka,
• Sophie Hytteballe,
• Torsten Piehler,
• Georg Meyer-Eppler,
• Filip Topić,
• Kari Rissanen,
• Marianne Engeser and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 432–441, doi:10.3762/bjoc.10.40

• homochiral assemblies by a factor of only two to three, this still reinforces our analysis – especially, if one takes into account that mass labelling in the periphery might cause differences in the ESI response factors that can cause slight deviations in the relative quantification of different components

[²H₂₆]-1-epi-Cubenol, a completely deuterated natural product from Streptomyces griseus

• Christian A. Citron and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 2841–2845, doi:10.3762/bjoc.9.319

• to slow down all metabolic processes in living organisms. Potential applications of completely labelled compounds from natural sources in structure elucidation, biosynthetic or pharmacokinetic investigations are discussed. Keywords: biosynthesis; deuterium; labelling; natural products; Streptomyces

• determination of the numbers of carbons and nitrogens in a natural product [28]. Therefore, such labelling experiments using a growth medium with a deuterium content of nearly 100% offer a suitable alternative to determine the number of hydrogens in an analyte, if no HRMS instrument is available. As pointed out

• in Bode’s study a labelling approach may even be more accurate for determination of the sum formula of a natural product, because a measured accurate mass may be in agreement with more than one molecular composition [28]. Completely deuterated compounds as exemplified by [2H26]-epi-cubenol in this

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• studies combined B3LYP density functional theory with labelling studies and revealed that the most likely pathway involves the formation of a tightly bound polar radical pair 3.31 resulting from

Gold(I)-catalyzed 6-endo hydroxycyclization of 7-substituted-1,6-enynes

• Ana M. Sanjuán,
• Alberto Martínez,
• Patricia García-García,
• Manuel A. Fernández-Rodríguez and
• Roberto Sanz

Beilstein J. Org. Chem. 2013, 9, 2242–2249, doi:10.3762/bjoc.9.263

• -(alkynyl)-(3-methylbut-2-enyl)benzenes 1. Gold(I)-catalyzed cycloisomerization of 1a. Initial experiments and proof of concept. Gold(I)-catalyzed hydroxycyclization of enynes 1m,n. Gold(I)-catalyzed methoxycyclization of selected 1,6-enynes 1 [45]. Labelling experiment and proposed mechanism. Effect of the

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• difference was observed between the performances of the two methods. Ferrocene-triazole conjugates play a crucial role in the labelling and detection of various systems, such as biomolecules, polymers, nanomaterials and supramolecular assemblies [70]. They also have potential applications in medicinal

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

• Reik Löser,
• Steffen Fischer,
• Achim Hiller,
• Martin Köckerling,
• Uta Funke,
• Aurélie Maisonial,
• Peter Brust and
• Jörg Steinbach

Beilstein J. Org. Chem. 2013, 9, 1002–1011, doi:10.3762/bjoc.9.115

• Chemistry Group, Albert-Einstein-Straße 3a, 18059 Rostock, Germany 10.3762/bjoc.9.115 Abstract 3-[18F]Fluoropropanesulfonyl chloride, a recently proposed prosthetic agent for fluorine-18 labelling, was prepared in a two-step radiosynthesis via 3-[18F]fluoropropyl thiocyanate as an intermediate. Two

• benzenesulfonate-based radiolabelling precursors were prepared by various routes. Comparing the reactivities of 3-thiocyanatopropyl nosylate and the corresponding tosylate towards [18F]fluoride the former proved to be superior accounting for labelling yields of up to 85%. Conditions for a reliable transformation

• the application of the 18F-fluoropropansulfonyl group to the labelling of compounds relevant as imaging agents for positron emission tomography (PET), the stability of N-(4-fluorophenyl)-3-fluoropropanesulfonamide against degradation catalysed by carboxylesterase was investigated and compared to that

Synthesis and stability study of a new major metabolite of γ-hydroxybutyric acid

• Ida Nymann Petersen,
• Jesper Langgaard Kristensen,
• Christian Tortzen,
• Torben Breindahl and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 641–646, doi:10.3762/bjoc.9.72

• ) of GHB glucuronides 2 (top) and d4-2 (bottom). As anticipated, methylene protons b and c are absent in d4-2 (cf. labelling in Scheme 3). 1H NMR spectra (500 MHz) of GHB glucuronide 2 in pH 4.8 buffer at t = 0 (rt) and t = 72 h (90 °C) by using a Watergate-type water suppression method (Supporting