Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• should be made to improve activity after internalization of the PDC. Overall, the investigations carried out up to this point provide a biological validation of the developed conjugate. The principally modular conjugation protocol for tubugis bears promise for further cancer targeting conjugates

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

• recently been approved or reached clinical validation can be found in Figure 2. If we analyze their mechanism of action, nearly all of them are currently being investigated as oncological treatments. For example, navitoclax (1, Figure 2), a Bcl-2/Bcl-XL inhibitor developed by Abbot Laboratories is

Halogen-containing thiazole orange analogues – new fluorogenic DNA stains

• Aleksey A. Vasilev,
• Meglena I. Kandinska,
• Stanimir S. Stoyanov,
• Stanislava B. Yordanova,
• David Sucunza,
• Juan J. Vaquero,
• Obis D. Castaño,
• Stanislav Baluschev and
• Silvia E. Angelova

Beilstein J. Org. Chem. 2017, 13, 2902–2914, doi:10.3762/bjoc.13.283

• ) in methanol for compounds 5a–d, TO and TO-7Cl in methanol. Supporting Information Supporting Information File 486: Characterisation data for the compounds: NMR and GS–MS spectra; validation of the theoretical computations; photostabilities at 532 nm. Acknowledgements The theoretical calculations

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• -regulation of Bim. Furthermore, the suggested interaction of mycolactone A/B with FKBP12 is supported by the protective effects of an excess of FK506 against mycolactone-induced apoptosis. However, further experimental validation of the mycolactone-FKBP12 interaction, e.g., by SPR, NMR or X-ray

Synthesis and metal binding properties of N-alkylcarboxyspiropyrans

• Alexis Perry and
• Christina J. Kousseff

Beilstein J. Org. Chem. 2017, 13, 1542–1550, doi:10.3762/bjoc.13.154

• constant for all merocyanine complexes of different metals, and indeed for different merocyanine complexes of the same metal. We thus sought initial validation of UV–vis data by direct comparison with data from 1H NMR, derived from merocyanine complexes of two non-paramagnetic metal cations, Mg2+ and Zn2

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• distortion and particular caution should be given to crystallographic reports where there is a wrong linkage distance specification or a mistaken anomer and handedness. Automated detection, building and validation of sugar models starting from X-ray diffraction data are being implemented [34]. Carbohydrate

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• of highly functionalized compounds. Novel approaches discussed in this review include metabolic engineering as well as site-directed mutagenesis to expand the natural terpene landscape. Focusing mainly on the validation of successful integration of engineered biosynthetic pathways into optimized

Self-optimisation and model-based design of experiments for developing a C–H activation flow process

• Alexander Echtermeyer,
• Yehia Amar,
• Jacek Zakrzewski and
• Alexei Lapkin

Beilstein J. Org. Chem. 2017, 13, 150–163, doi:10.3762/bjoc.13.18

• 98.72%. The experimentally obtained yields in the validation of the two sets of conditions were determined to be >99%, which is caused by the uncertainty of the applied GC method including sample preparation, which lead to ±1% variance in the yield value. The algorithm is not expected to exhibit fast

• of samples needed in the experiment and the statistical t-test results. Results of the parameter estimation showing the final values, initial guesses, 95% confidence intervals (CI) and t-values for each of the 8 parameters. Experimental conditions and results of the experimental validation of the two

Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934

• Veronika Ulrich,
• Clara Brieke and
• Max J. Cryle

Beilstein J. Org. Chem. 2016, 12, 2849–2864, doi:10.3762/bjoc.12.284

• the models where appropriate. TLS input files were generated using the TLS-Motion Determination Server [59][60]. Structure validation was performed using MOLPROBITY [61] and PROCHECK [62]. Structure-based sequence alignments were carried out with SSM [63] as implemented in COOT and comparisons to

cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

• Dimpee Gogoi,
• Runjun Devi,
• Pallab Pahari,
• Bipul Sarma and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2016, 12, 2816–2822, doi:10.3762/bjoc.12.280

• might undergo a competitive semipinacol rearrangement to give ring contracted product 11. With all these concerns in our mind, we started this work first with the synthesis of compound (±)-5a from glycidyl ether (±)-6a as a model reaction for validation and optimization studies. (±)-6a was synthesized

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

• Viktor Ilkei,
• András Spaits,
• Anita Prechl,
• Áron Szigetvári,
• Zoltán Béni,
• Miklós Dékány,
• Csaba Szántay Jr,
• Judit Müller,
• Árpád Könczöl,
• Ádám Szappanos,
• Attila Mándi,
• Sándor Antus,
• Ana Martins,
• Attila Hunyadi,
• György Tibor Balogh,
• György Kalaus (†),
• Hedvig Bölcskei,
• László Hazai and
• Tibor Kurtán

Beilstein J. Org. Chem. 2016, 12, 2523–2534, doi:10.3762/bjoc.12.247

• the stereochemical studies of flavanoid alkaloids, the solution TDDFT–ECD calculation method [6] was applied to 2a–d and 3a–d. For the validation of our computational approach on flavonoids, the ECD spectra of (R)-naringenin ((R)-1), the building blocks of dracocephins A and B, were calculated first

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• of phosphorylation, time-dependent CD (circular dichroism) measurements were performed. To ensure comparable and reproducible starting conditions, a disaggregation and concentration validation assay using HFIP (1,1,1,3,3,3-hexafluoropropan-2-ol) was performed. Thus, all aggregates that may have

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• multiple structural isomers of bridged polycycles from a common intermediate offer multiple advantages: saved time and effort by avoiding the validation of new strategies for each target, accumulated understanding of the key reactions in the strategy for higher yields and improved efficiency, and rapid

Is conformation a fundamental descriptor in QSAR? A case for halogenated anesthetics

• Maria C. Guimarães,
• Mariene H. Duarte,
• Josué M. Silla and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2016, 12, 760–768, doi:10.3762/bjoc.12.76

• structures encode biological activities. A previous study using log P (the octanol/water partition coefficient) as descriptor showed a good correlation with pMAC [21], but the resulting model was not validated. Thus, the present study provided an internal (through leave-one-out cross-validation) and external

• validation to attest the reliability of the MIA-QSAR model. This was checked through the respective root mean square errors (RMSE) and the determination coefficients for the plot of actual vs predicted pMAC (q2 and r2test > 0.5 are considered acceptable). Also, since the MIA-QSAR model was obtained from PLS

Art, auto-mechanics, and supramolecular chemistry. A merging of hobbies and career

• Eric V. Anslyn

Beilstein J. Org. Chem. 2016, 12, 362–376, doi:10.3762/bjoc.12.40

• , and quantitate concentrations, would be a large validation of the method. To accomplish this we used serum albumins as the cross-reactive receptors, paired with a series of hydrophobic indicators [107]. The method worked extremely well (Figure 10C), and we are currently pursuing the analysis of

• -well plates [107]. The array components consisted of BSA and HSA (100 µM), glyceride (90 µM), DNSA (60 µM), ANS (60 µM), NBD-FA (60 µM), metathesized glyceride (90 µM), AF (100 µM), and DNSA (60 µM) in phosphate buffer with <5% (v/v) THF. Cross-validation: 98%. Two seemingly impossible targets to make

Learning from the unexpected in life and DNA self-assembly

• Jennifer M. Heemstra

Beilstein J. Org. Chem. 2015, 11, 2713–2720, doi:10.3762/bjoc.11.292

• validation of our hypothesis regarding the thermodynamics of split aptamer assembly. In the short term, this allowed us to overcome the challenge of background signal by reducing the ionic strength, and we were delighted to observe dose-dependent ligation of the split aptamer fragments with increasing

The Beilstein Journal of Organic Chemistry and the changing face of scientific publishing

• Martin G. Hicks and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2015, 11, 2242–2244, doi:10.3762/bjoc.11.242

• computer-readable formats for validation and searching. Reading patterns have significantly changed. The number of articles published per year has significantly increased over the last decades, thus routinely “keeping up with the literature” is no longer possible as it was in the past. However, since

Chiroptical properties of 1,3-diphenylallene-anchored tetrathiafulvalene and its polymer synthesis

• Masashi Hasegawa,
• Junta Endo,
• Seiya Iwata,
• Toshiaki Shimasaki and
• Yasuhiro Mazaki

Beilstein J. Org. Chem. 2015, 11, 972–979, doi:10.3762/bjoc.11.109

• validation of the absolute configurations based on the TD-DFT method. Although the observed Cotton effect associated with TTF moieties is relatively weak, each chiral allene is stable towards the racemization under ambient light. A chiral copolymer based on TTF and a chiral 1,3-diphenylallene as the main

Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization

• William H. Hersh

Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19

• differences in rates of diastereomer decomposition. Calculation of acylphosphonite inversion barrier. As described in the Introduction, inversion barriers for phosphines, acylphosphines, and phosphites are known. These were calculated first for validation of the method. The structures of chiral phosphine 18

Three-component synthesis of C₂F₅-substituted pyrazoles from C₂F₅CH₂NH₂·HCl, NaNO₂ and electron-deficient alkynes

• Pavel K. Mykhailiuk

Beilstein J. Org. Chem. 2015, 11, 16–24, doi:10.3762/bjoc.11.3

• and Discussion Validation and optimization To challenge the putative transformation, the simple mono-substituted alkyne 1 with one electron-withdrawing CO2Me-group (EWG) was selected. A mixture of alkyne 1, C2F5CH2NH2·HCl (1.0 equiv) [48] and NaNO2 (2.0 equiv) in water/dichloromethane was stirred at

Thermal and oxidative stability of the Ocimum basilicum L. essential oil/β-cyclodextrin supramolecular system

• Daniel I. Hădărugă,
• Nicoleta G. Hădărugă,
• Corina I. Costescu,
• Ioan David and
• Alexandra T. Gruia

Beilstein J. Org. Chem. 2014, 10, 2809–2820, doi:10.3762/bjoc.10.298

• structures were also considered (e.g., 1 – for monocyclic structure, 2 – for bicyclic, etc.). The PCA analysis was performed by using the centered data and cross validation method. The main compounds identified in raw O. basilicum L. essential oils (a) and the degradation reactions for some labile compounds

Lateral ordering of PTCDA on the clean and the oxygen pre-covered Cu(100) surface investigated by scanning tunneling microscopy and low energy electron diffraction

• Stefan Gärtner,
• Benjamin Fiedler,
• Oliver Bauer,
• Antonela Marele and
• Moritz M. Sokolowski

Beilstein J. Org. Chem. 2014, 10, 2055–2064, doi:10.3762/bjoc.10.213

• coupling of the molecules to the substrate on the two different sites. We note however that the observation of the STM contrast is not a firm argument for identical adsorption sites and may require validation by other methods. Under the condition that one PTCDA molecule is positioned at the edge and one at

Rapid pseudo five-component synthesis of intensively blue luminescent 2,5-di(hetero)arylfurans via a Sonogashira–Glaser cyclization sequence

• Fabian Klukas,
• Alexander Grunwald,
• Franziska Menschel and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 672–679, doi:10.3762/bjoc.10.60

• oxidation potential E1/20/+1. This gap was estimated by the cross-section of the absorption and emission spectra. For the missing oxidation potentials of 2f, 2g, 2m, and 2l the HOMO and LUMO energies were determined by DFT calculations [48]. For validation of the experimental and computational data the

Plakilactones G and H from a marine sponge. Stereochemical determination of highly flexible systems by quantitative NMR-derived interproton distances combined with quantum mechanical calculations of ¹³C chemical shifts

• Simone Di Micco,
• Angela Zampella,
• Maria Valeria D’Auria,
• Carmen Festa,
• Simona De Marino,
• Raffaele Riccio,
• Craig P. Butts and
• Giuseppe Bifulco

Beilstein J. Org. Chem. 2013, 9, 2940–2949, doi:10.3762/bjoc.9.331

• -dehydroderivative (3) [23], that is likely the biosynthetic precursor of all side-chain-oxidized derivatives belonging to this family, this information was not considered for the validation of our protocol and all four stereocenters for plakilactones G and H have been investigated. Plakilactone G (1) was isolated