Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• introduce a wide variety of substituents on 1,4-disubstituted 1,2,3-triazoles from the organic azide or terminal alkyne starting materials [1][2]. These Huisgen reactions [13] facilitate rapid drug screening by allowing for tracking in biological systems and the exploration of structure-activity

• relationships [10][14][15][16][17][18][19]. Propargylamines are a popular choice for the terminal alkyne component and form highly selective inhibitors (Figure 1) [2]. Due to the difficulty of forming tetrasubstituted propargylamines, the incorporation of deprotectable variants into triazoles is extremely rare

Antioxidant potential of curcumin-related compounds studied by chemiluminescence kinetics, chain-breaking efficiencies, scavenging activity (ORAC) and DFT calculations

• Adriana K. Slavova-Kazakova,
• Silvia E. Angelova,
• Timur L. Veprintsev,
• Petko Denev,
• Davide Fabbri,
• Maria Antonietta Dettori,
• Maria Kratchanova,
• Vladimir V. Naumov,
• Aleksei V. Trofimov,
• Rostislav F. Vasil’ev,
• Giovanna Delogu and
• Vessela D. Kancheva

Beilstein J. Org. Chem. 2015, 11, 1398–1411, doi:10.3762/bjoc.11.151

• reported for different plant extracts. Model 4: DFT calculations In order to explain the structure–activity relationships of the hydroxylated biphenyls and their corresponding monomers, we have optimized the geometries of the compounds and possible phenoxyl radical species of the parent compounds. The

Peptide–polymer ligands for a tandem WW-domain, an adaptive multivalent protein–protein interaction: lessons on the thermodynamic fitness of flexible ligands

• Katharina Koschek,
• Vedat Durmaz,
• Oxana Krylova,
• Marek Wieczorek,
• Shilpi Gupta,
• Martin Richter,
• Alexander Bujotzek,
• Christina Fischer,
• Rainer Haag,
• Christian Freund,
• Marcus Weber and
• Jörg Rademann

Beilstein J. Org. Chem. 2015, 11, 837–847, doi:10.3762/bjoc.11.93

• used for the construction of peptide–polymer conjugates [11][12], however, a systematic comparison of the different polymeric materials with respect to the structure–activity relationships is missing so far. The goal of this contribution is to synthesize and compare flexible multivalent ligands for an

• understanding of structure–activity relationships of polymeric ligands. For this purpose, the thermodynamics and the stoichiometry of protein binding events were determined experimentally for all multivalent ligands. Finally, atomistic molecular dynamics simulations were conducted in order to rationalize the

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• overcome these drawbacks and to enhance the activity. In addition, their structure–activity relationships were studied to gain better insight into the mode of action. The general synthesis of curcumin itself (Scheme 1) [23][24] requires masking of the reactive methylene group of the acetylacetone moiety by

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• desirable as the incorporation of conformationally constrained α-amino acids such as 3 into peptides is frequently used to study structure–activity relationships [38][39][40]. Several methods have been developed for the preparation of analogues of β-methylphenylalanine in enantiopure form. These include

• were 37 and 45% lower than those of hormaomycin (1) itself. Further exploration of structure–activity relationships of the hormaomycins would be required to prepare new antiparasitic lead compounds. Conclusion At first sight, the oligopeptide assembly leading to hormaomycin does not appear to be a very

Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators

• Michail Syrpas,
• Ewout Ruysbergh,
• Christian V. Stevens,
• Norbert De Kimpe and
• Sven Mangelinckx

Beilstein J. Org. Chem. 2014, 10, 2539–2549, doi:10.3762/bjoc.10.265

• ability of this biosensor to respond to a broad range of chain lengths and functionalization makes it a good choice for the study of structure–activity relationships of synthesized analogues. The ability of the natural AHLs 3 and their halogenated analogues 6, 8 and 11 to induce fluorescence was expressed

Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars

• Christopher Albler,
• Ralph Hollaus,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2014, 10, 2230–2234, doi:10.3762/bjoc.10.231

• allowing for an evaluation of structure–activity relationships. Results and Discussion We started our reaction sequence with an indium-mediated allylation of unprotected carbohydrates using D-arabinose (1a), D-galactose (1b) and D-glucose (1c) as starting materials. The Barbier-type chain elongation

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• nanoparticle) of the sulfated pyrans [26][27]. We were therefore interested to prepare inhibitors offering only a small number of ligands to get better information about structure–activity relationships and to study the influence of the flexible and rigid spacer units. In this report we present methods for the

Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

• Andreas Gansäuer,
• Andreas Okkel,
• Lukas Schwach,
• Laura Wagner,
• Anja Selig and
• Aram Prokop

Beilstein J. Org. Chem. 2014, 10, 1630–1637, doi:10.3762/bjoc.10.169

• started our investigation with the preparation of azide-substituted cationic titanocenes. To this end, the titanocene carboxylates 1–3 shown in Figure 1 were employed as substrates because their substitution pattern should allow a first simple assessment of structure–activity relationships. The compounds

Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

• Yoann M. Chabre,
• Alex Papadopoulos,
• Alexandre A. Arnold and
• René Roy

Beilstein J. Org. Chem. 2014, 10, 1524–1535, doi:10.3762/bjoc.10.157

• quantitative structure–activity relationships (QSARs). In most of the studies related to aglycon modifications, it was concluded that aromatic glycosides possessed improved binding properties due to the ubiquitous presence of aromatic amino acids in the cognate binding sites [23][24][25]. This is also

Physalin H from Solanum nigrum as an Hh signaling inhibitor blocks GLI1–DNA-complex formation

• Midori A. Arai,
• Kyoko Uchida,
• Samir K. Sadhu,
• Firoj Ahmed and
• Masami Ishibashi

Beilstein J. Org. Chem. 2014, 10, 134–140, doi:10.3762/bjoc.10.10

• physalins were found to be cytotoxic to cancer cells with an aberrant Hh signaling pathway and inhibited the expression of Hh signaling-related proteins. Structure–activity relationships were observed in the Hh inhibitory activity of physalins and the left part of the structure was found to have an

Studies toward bivalent κ opioids derived from salvinorin A: heteromethylation of the furan ring reduces affinity

• Thomas A. Munro,
• Wei Xu,
• Douglas M. Ho,
• Lee-Yuan Liu-Chen and
• Bruce M. Cohen

Beilstein J. Org. Chem. 2013, 9, 2916–2924, doi:10.3762/bjoc.9.328

• for linked, fused or merged bivalent derivatives of 1. Keywords: allotopic; bivalent ligand; designed multiple ligand; JDTic; κ-opioid receptor; natural products; Salvinorin A; Introduction The structure–activity relationships of salvinorin A (1), a potent and selective κ (kappa) opioid, have been

• work, all published mutagenesis-based models placed the furan ring in contact with Tyr3207.43 [1]. This interaction is plausible in light of the structure–activity relationships of opioid antagonists. In JDTic, the N-substituent of the HPP moiety interacts with Tyr3207.43 [7], and N-furanylalkyl

The total synthesis of D-chalcose and its C-3 epimer

• Jun Sun,
• Song Fan,
• Zhan Wang,
• Guoning Zhang,
• Kai Bao and
• Weige Zhang

Beilstein J. Org. Chem. 2013, 9, 2620–2624, doi:10.3762/bjoc.9.296

• sourced material and unsatisfactory overall yield. As part of our study concerning the structure–activity relationships and chemistry of new antibiotics, we sought to develop a reliable and efficient synthetic route starting from inexpensive, commercial sources to provide access to chalcose. We describe a

Synthesis and antibacterial activity of monocyclic 3-carboxamide tetramic acids

• Yong-Chul Jeong and
• Mark G. Moloney

Beilstein J. Org. Chem. 2013, 9, 1899–1906, doi:10.3762/bjoc.9.224

• influenzae, including an efflux-negative strain, and 2 strains of Escherichia coli, including an efflux-negative strain (Table 2). Relevant physicochemical properties of the analogues are also shown in Table 3. These were used to elaborate structure–activity relationships (SAR) [26]. In the assay against

Synthesis and quantitative structure–activity relationship study of substituted imidazophosphor ester based tetrazolo[1,5-b]pyridazines as antinociceptive/anti-inflammatory agents

• Wafaa M. Abdou,
• Neven A. Ganoub and
• Eman Sabry

Beilstein J. Org. Chem. 2013, 9, 1730–1736, doi:10.3762/bjoc.9.199

• . The anti-inflammatory and the antinociceptive properties of the prepared compounds were screened and the structure–activity relationships were studied. The anti-inflammatory properties of many tetrazole [21][22][23] and pyridazine derivatives have also led to their clinical application as NSAIDs (e.g

Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues

• Xu-Wen Li,
• Jennifer Herrmann,
• Yi Zang,
• Philippe Grellier,
• Soizic Prado,
• Rolf Müller and
• Bastien Nay

Beilstein J. Org. Chem. 2013, 9, 1551–1558, doi:10.3762/bjoc.9.176

• some ring as opposed to chain analogues, allowing for the description of structure–activity relationships. Biological screening of the analogues showed antiparasitic, cytotoxic, antibacterial and antifungal activities, and depletion of the mitochondrial membrane potential. The strongest activity was

ML212: A small-molecule probe for investigating fluconazole resistance mechanisms in Candida albicans

• Willmen Youngsaye,
• Cathy L. Hartland,
• Barbara J. Morgan,
• Amal Ting,
• Partha P. Nag,
• Benjamin Vincent,
• Carrie A. Mosher,
• Joshua A. Bittker,
• Sivaraman Dandapani,
• Michelle Palmer,
• Luke Whitesell,
• Susan Lindquist,
• Stuart L. Schreiber and
• Benito Munoz

Beilstein J. Org. Chem. 2013, 9, 1501–1507, doi:10.3762/bjoc.9.171

• fungal cells. A substituted indazole possessing the desired bioactivity profile was selected for further development, and initial investigation of structure–activity relationships led to the discovery of ML212. Keywords: antifungal; Candida albicans; chemosensitizer; fluconazole; Molecular Libraries

• closely related analogues were prepared to enable investigation of possible structure–activity relationships (SAR) [18]. In addition to indazole 1, two other structurally distinct scaffolds (2 and 3) were also selected for follow-up studies and those works are communicated elsewhere [19][20]. Chemistry

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• efforts to develop chemical probes to detect pathophysiological hallmarks of AD, such as amyloid-β plaques, for diagnosis and monitoring of therapeutic efficacy. This review provides a survey of chemical probes developed to date for AD with emphasis on synthetic methodologies and structure–activity

• relationships with regards to affinity for target and brain kinetics. Several probes discussed herein show particularly promising results and will be of immense value moving forward in the fight against AD. Keywords: Alzheimer’s disease; in vivo detection; near-infrared fluorescence probes; PET/SPECT imaging

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

• –activity relationships (SAR) through analogue synthesis [9]. This probe was discovered after two separate screening campaigns totaling ~110,000 compounds. At concentrations up to 8 μM, 4 failed to suppress PKCβ and PKCθ (the PKC family members implicated in TCR/BCR signaling) and IKKβ, while known PKC and

• other NF-κB activation pathways such as those including the cytosolic proteins CARMA1, Bcl-10, MALT1, TRAF6 and Ubc13 [8]. The first probe identified within this series was the benzimidazole ML029 (4), which exhibited an IC50 of 0.07 μM in the HEK 293 cell assay with corresponding well-defined structure

Utilizing the σ-complex stability for quantifying reactivity in nucleophilic substitution of aromatic fluorides

• Magnus Liljenberg,
• Tore Brinck,
• Tobias Rein and
• Mats Svensson

Beilstein J. Org. Chem. 2013, 9, 791–799, doi:10.3762/bjoc.9.90

• assessment of reactivity: property- or descriptor-based and direct modeling of the PES, especially of the rate-determining TS. The first type is generally termed QSAR (quantitative structure–activity relationships), where experimentally known or calculated properties are fitted to observed reactivities

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

• dopamine receptors. PLG peptidomimetic design Although several studies of structure–activity relationships on PLG had been carried out early on [12][13][14], these studies did not provide information about the conformation PLG adopts to produce its pharmacological actions. NMR spectroscopic studies [15

Asymmetric synthesis of host-directed inhibitors of myxoviruses

• Terry W. Moore,
• Kasinath Sana,
• Dan Yan,
• Pahk Thepchatri,
• John M. Ndungu,
• Manohar T. Saindane,
• Mark A. Lockwood,
• Michael G. Natchus,
• Dennis C. Liotta,
• Richard K. Plemper,
• James P. Snyder and
• Aiming Sun

Beilstein J. Org. Chem. 2013, 9, 197–203, doi:10.3762/bjoc.9.23

• benzimidazole nitrogen in these crystal structures results in pseudo seven-membered rings. Whether this conformation is biologically relevant is unknown. Structure–activity relationships A small set of compounds was synthesized based on variations of 1 by replacing the p-methoxyphenyl group with other

The multicomponent approach to N-methyl peptides: total synthesis of antibacterial (–)-viridic acid and analogues

• Ricardo A. W. Neves Filho,
• Sebastian Stark,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2012, 8, 2085–2090, doi:10.3762/bjoc.8.234

• , with competitive Passerini reaction in the latter case [28][29]. With the general process in place, the MCR approach was employed to generate a library of synthetic derivatives of 1 with the hope of gaining a first glimpse of structure–activity relationships (SAR), and to give hints for further

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• features applying also to so-called membrane-transducing peptides [11][12]. Results Preparation of phallotoxin derivatives Attachment sites in phalloidin (Figure 1) for conjugation with uptake-mediating moieties were chosen based on our knowledge of structure–activity relationships in phalloidin [1]: As

A macrolactonization approach to the total synthesis of the antimicrobial cyclic depsipeptide LI-F04a and diastereoisomeric analogues

• James R. Cochrane,
• Dong Hee Yoon,
• Christopher S. P. McErlean and
• Katrina A. Jolliffe

Beilstein J. Org. Chem. 2012, 8, 1344–1351, doi:10.3762/bjoc.8.154

• difficult to determine structure–activity relationships [7][8]. More recently, the solid-phase synthesis of a number of analogues of the fusaricidins has been reported. However, in all cases, the side chain 3-hydroxy group was not incorporated into the structure [9]. By total synthesis of both side-chain