Investigating the continuous synthesis of a nicotinonitrile precursor to nevirapine

• Ashley R. Longstreet,
• Suzanne M. Opalka,
• Brian S. Campbell,
• B. Frank Gupton and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2013, 9, 2570–2578, doi:10.3762/bjoc.9.292

• a completely continuous process provides the opportunity to advance process chemistry/technology, a new process can often require significant investment for regulatory validation. We wish to implement our technology as quickly as feasible and to do so we want to avoid potential regulatory problems

Organocatalytic asymmetric selenofunctionalization of tryptamine for the synthesis of hexahydropyrrolo[2,3-b]indole derivatives

• Qiang Wei,
• Ya-Yi Wang,
• Yu-Liu Du and
• Liu-Zhu Gong

Beilstein J. Org. Chem. 2013, 9, 1559–1564, doi:10.3762/bjoc.9.177

• validation of our hypothesis. Encouragingly, the reaction proceeded smoothly in the presence of 10 mol % of the phosphoric acids evaluated under the assistance of 5 Å molecular sieves. Apparently, the stereoselectivity depended on the N-protecting group of tryptamine 1. When nitrogen atoms of the tryptamine

Space filling of β-cyclodextrin and β-cyclodextrin derivatives by volatile hydrophobic guests

• Sophie Fourmentin,
• Anca Ciobanu,
• David Landy and
• Gerhard Wenz

Beilstein J. Org. Chem. 2013, 9, 1185–1191, doi:10.3762/bjoc.9.133

• A, respectively, according to Equation 1, as derived in Supporting Information File 1 [36]. For a validation of the method, the whole concentration dependence of the integrated GC signal intensity was measured as a function of the CD concentration [CD]0 in the case of β-CD. The data points were

Study on the total synthesis of velbanamine: Chemoselective dioxygenation of alkenes with PIFA via a stop-and-flow strategy

• Huili Liu,
• Kuan Zheng,
• Xiang Lu,
• Xiaoxia Wang and
• Ran Hong

Beilstein J. Org. Chem. 2013, 9, 983–990, doi:10.3762/bjoc.9.113

• synthetic targets. Conclusion In summary, with a comprehensive validation of PIFA-promoted cyclization of alkenes, a synthetically useful desymmetrization approach via the dioxygenation of alkenes was developed. The “stop-and-flow” strategy allows us to easily functionalize seco-dienes step-by-step

Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• validation using a panel of known receptor and kinase-based counter screens [7]. Because activation of NF-κB is known to be initiated through protein kinase C (PKC), we hypothesized that selectivity could be possible by the fact that PKC activation occurs downstream from cell membrane antigen and growth

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• development and validation of this series of small molecules may prove valuable for future therapeutic development. Another mechanism to attenuate the toxicity of TDP-43 is to prevent its aggregation into intercellular inclusions. In a study by Parker et al. [38], treatment of SH-SY5Y cells with paraquat to

• prove to be efficacious in ALS patients. Various screening approaches and targeted drug design, as outlined in this review, have identified a number of small molecules that will prove useful in the discovery and validation of novel cellular targets for the treatment of ALS (Figure 15). Figure 15

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

• about putting this proposal to the test using quantum chemical calculations [8]. Results and Discussion Structure validation: We first computed 1H and 13C chemical shifts for 1 to assure ourselves that the assigned structure was reasonable [9][10]. Our calculated chemical shifts and the reported data

Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

• Matthias G. J. Baud,
• Thomas Leiser,
• Vanessa Petrucci,
• Mekala Gunaratnam,
• Stephen Neidle,
• Franz-Josef Meyer-Almes and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2013, 9, 81–88, doi:10.3762/bjoc.9.11

• buffered conditions of the assay and direct cleavage of the acetyl group by the deacetylase enzyme. It therefore remains highly plausible that the thioacetate group can function as a potent zinc-binding group in its own right. While this hypothesis requires further validation, it opens up exciting new

Automated three-component synthesis of a library of γ-lactams

• Erik Fenster,
• David Hill,
• Oliver Reiser and
• Jeffrey Aubé

Beilstein J. Org. Chem. 2012, 8, 1804–1813, doi:10.3762/bjoc.8.206

• synthesis The combined sequence was next attempted as a rehearsal 2 × 3 × 3 validation library by using a Chemspeed Accelerator SLT-100 synthesizer (Table 3). In general, substrates which varied in their steric and electronic nature were chosen (alkyl and aryl groups). By using the three-step single-pot

• validation efforts demonstrated both the success of the one-pot automated method, as well as the scope of substrates suitable for a larger library set. With these considerations, we planned for a 4 × 8 × 8 = 256 member library of γ-lactams 6 on the Chemspeed platform with the conditions evaluated in the

Exploring chemical diversity via a modular reaction pairing strategy

• Joanna K. Loh,
• Sun Young Yoon,
• Thiwanka B. Samarakoon,
• Alan Rolfe,
• Patrick Porubsky,
• Benjamin Neuenswander,
• Gerald H. Lushington and
• Paul R. Hanson

Beilstein J. Org. Chem. 2012, 8, 1293–1302, doi:10.3762/bjoc.8.147

• aforementioned 80-member library. Validation and library generation With the optimized conditions in hand, a 20-member validation library was prepared by using scaffolds selected from 1–5 and amines {1–10} in DMSO (0.5 M) at 180 °C for 50 min, in 1 dram vials, using the Anton Parr Synthos 3000® platform (Table 2

• ) [41]. Upon completion, the crude reaction mixtures were diluted, filtered through silica SPE, and purified by automated mass-directed HPLC. Library validation was essential to assess both substrate and reaction scope, along with evaluating the application of automated mass-directed HPLC as the final

• mg), and to retain a sample (10 mg) for follow-up evaluation or to resupply the NIH MLPCN. Evaluation of this validation library demonstrated that all 20 members were successfully prepared (average purity = 99.7%, yield = 70%, quantity = 73.0 mg) in the desired sultam final masses, with all 20

On the proposed structures and stereocontrolled synthesis of the cephalosporolides

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2012, 8, 1287–1292, doi:10.3762/bjoc.8.146

• of zinc salts between the spiroketal oxygen and appropriately positioned hydroxyls overrides normal steric biases to guide the formation of the spiroketal. Cephalosporolide E was targeted for validation of this approach. There are three main differences between cephalosporolides E and H (Figure 2

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

• Kalicharan Chattopadhyay,
• Erik Fenster,
• Alexander J. Grenning and
• Jon A. Tunge

Beilstein J. Org. Chem. 2012, 8, 1200–1207, doi:10.3762/bjoc.8.133

• , analysis of the library yields indicates that N-arylpiperazines A8 and A9 in addition to propargylamine A15 were the most problematic. Perhaps unsurprisingly, the amine that provided the highest yields and highest success rate was diallyl amine, which was used for initial validation of the Chemspeed method

The use of glycoinformatics in glycochemistry

• Thomas Lütteke

Beilstein J. Org. Chem. 2012, 8, 915–929, doi:10.3762/bjoc.8.104

• SugaBase or manually entered from the literature. Glycosciences.DB also contains information on carbohydrate 3D structures that are available in the Protein Data Bank (PDB, [40]). Extraction and validation of carbohydrate data from PDB entries is automated to a large extent and therefore requires only

• significantly lower quality than the protein parts [26][84][85][86]. Reasons for this are both the greater complexity of carbohydrates, and the fact that, while numerous validation tools are available for protein structures [87], only a few programs exist to validate carbohydrate 3D structures. The PDB

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

• interaction of GSF with integrins. To find possible binding sites for GSF, we used a “blind docking” approach to screen the protein surface of the extracellular domain of αvβ3, the crystal structure of which was published by Xiong et al. [26]. In an initial validation study, we performed multiple blind