BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• production in the presence of LPS; at 100 µM concentration of construct 6, the level of NO raised up to 30 µM. In further biological evaluation, we found that construct 6 was efficiently localized inside human U-2 OS and HeLa cancer cells. The encapsulation of construct 6 into liposomes resulted in

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• configured trienes present in polyketides [12][13][14][15]. Furthermore, we show how the intermediate p-methide quinone can be exploited to also prepare elansolid B2 (3). The improved synthesis allows more easily preparing analogues of the elansolids for further biological evaluation. Experimental General

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• these scarce natural products for biological evaluation, but also in supplying novel analogues with tailored functional properties to decipher the target inhibitor interactions at a molecular level. Finally, the total syntheses of the Menche and Trauner group were also of key importance to assign the

Synthesis of D-manno-heptulose via a cascade aldol/hemiketalization reaction

• Yan Chen,
• Xiaoman Wang,
• Junchang Wang and
• You Yang

Beilstein J. Org. Chem. 2017, 13, 795–799, doi:10.3762/bjoc.13.79

• construction of the differentially protected ketoheptose building block, which was finally converted into D-manno-heptulose for subsequent biological evaluation. Although the synthesis of D-manno-heptulose (5% overall yield, 13 steps) is not so efficient as the Thiem’s method (59% overall yield, 5 steps), the

Isoxazole derivatives as new nitric oxide elicitors in plants

• Anca Oancea,
• Emilian Georgescu,
• Florentina Georgescu,
• Alina Nicolescu,
• Elena Iulia Oprita,
• Catalina Tudora,
• Lucian Vladulescu,
• Marius-Constantin Vladulescu,
• Florin Oancea and
• Calin Deleanu

Beilstein J. Org. Chem. 2017, 13, 659–664, doi:10.3762/bjoc.13.65

• orchestration of various plant physiological responses, playing an important role in the regulation of interactions between plant and microorganisms and in plant defense mechanisms against stresses [18][19]. Consequently, there is interest in the biological evaluation of further isoxazole derivatives. Many

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• biological evaluation, the compound (S,S)-6e has shown an intermolecular energy value comparable with that of the co-crystallized ligand (MI63 analogue). In addition to a lowest binding energy and intermolecular energy of docking success, we have also performed a visual inspection to confirm that all the

Identification, synthesis and mass spectrometry of a macrolide from the African reed frog Hyperolius cinnamomeoventris

• Markus Menke,
• Pardha Saradhi Peram,
• Iris Starnberger,
• Walter Hödl,
• Gregory F.M. Jongsma,
• David C. Blackburn,
• Mark-Oliver Rödel,
• Miguel Vences and
• Stefan Schulz

Beilstein J. Org. Chem. 2016, 12, 2731–2738, doi:10.3762/bjoc.12.269

• towards a biological evaluation of the gland secretion and its compounds to understand their real function in the behavior of the frogs. Although no experimental evidence has been obtained so far, the close association of the innervation of the gland with the mating period, its location and use during

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• the alkyne employed. Herein, we report the results of the synthesis and in vitro biological evaluation on the purified human recombinant cN-II of a series of beta-hydroxyphosphonate ribonucleosides including as nucleobases 4-substituted-1,2,3-triazoles (Figure 1). Results and Discussion Chemistry The

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• arylamines were found to be effective in this reaction. Eventually, the biological evaluation of the (2H-isoindol-1-yl)phosphonates 74 revealed their potential as HCT-116 inhibitors. 2.2.4 Pyrazolyl- and oxazolylphosphonates: A series of modified Kabachnik–Fields condensations based on the reaction of 6

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• contain two biologically important structural scaffolds, namely the 3-hydroxyoxindole and coumarin, which could be potentially used for further biological evaluation or serve as starting points in drug discovery pursuits. A highly stereoselective Mukaiyama–aldol reaction was reported by Zhou and co

• (Scheme 51) [69]. The protocol developed was also suitable for a gram scale synthesis, thus shows promising in the constrction of analogs of natural product trisindoline for further biological evaluation. In this work, the authors obtained diindolyloxindoles, in which the oxindole motif was attached to

Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• experimentally known MIC values of eight linezolid analogues were used in order to crosscheck the robustness of our model. In a final step, this benchmarking led to the prediction of several new and promising lead compounds. Synthesis and biological evaluation of the new compounds are on the way. Keywords

Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

• Camilla Matassini,
• Stefania Mirabella,
• Andrea Goti,
• Inmaculada Robina,
• Antonio J. Moreno-Vargas and
• Francesca Cardona

Beilstein J. Org. Chem. 2015, 11, 2631–2640, doi:10.3762/bjoc.11.282

• received an increasing attention by the scientific community, rapidly emerging as a hot topic in glycoscience. Three excellent recent reviews collect the efforts of the researchers both in the synthesis and in the biological evaluation of the new multivalent structures [8][9][10]. In particular, remarkable

• thus employed in further biological evaluation. In order to evaluate the relative inhibitory activity enhancement of these new multimeric systems, a proper monovalent counterpart was also synthesized. In particular, starting from azidopiperidine 4, the CuAAC reaction was performed with propargylamine

• moiety, the CuAAC approach was investigated either on the protected and deprotected iminosugar, with different purification techniques employed in both cases. A monomer reference compound was also synthesized for comparison. Biological evaluation against a panel of eleven commercially available

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

• Hang Ren,
• Haoyun An,
• Paul J. Hatala,
• William C. Stevens Jr,
• Jingchao Tao and
• Baicheng He

Beilstein J. Org. Chem. 2015, 11, 2509–2520, doi:10.3762/bjoc.11.272

• University of Chicago Medical Center, Chicago, Illinois 60637, USA 10.3762/bjoc.11.272 Abstract A unified synthetic strategy accessing novel 3'-fluorinated purine nucleoside derivatives and their biological evaluation were achieved. Novel 3’-fluorinated analogues were constructed from a common 3’-deoxy-3

• direct glycosylation for the synthesis of 3’-fluorine modified guanosine derivatives is highly advantageous compared to the previously reported methods utilizing orthogonal protecting groups, selective deprotection, and fluorination of the starting guanosine [34]. Biological evaluation Newly synthesized

• inhibitory activity, but other derivatives did not show detectable activity against the tested tumor cell lines. Antiviral and other biological evaluation of these 3’-fluorine modified nucleosides is in progress and will be reported in due course. Conclusion The 6-chloropurine, 2,6-dichloropurine, and 2

Synthesis of constrained analogues of tryptophan

• Elisabetta Rossi,
• Valentina Pirovano,
• Marco Negrato,
• Giorgio Abbiati and
• Monica Dell’Acqua

Beilstein J. Org. Chem. 2015, 11, 1997–2006, doi:10.3762/bjoc.11.216

• -carbon atom of the amino acid function and the C-2 carbon of the indole ring (tetrahydrocarbazole derivatives). The first report on the synthesis and biological evaluation of a constrained tryptophan analogue appeared in the literature in 1973 [11]. Maki and co-workers reported the synthesis of 3-amino

• from the biological evaluation to the chemistry of tryptophan analogues, the above described two categories were synthesized according to the Pictet–Spengler reaction or by Fischer indole synthesis [11][12][13][14]. However, Fischer indolization suffers from the lack of regioselectivity depending on

SmI₂-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen B

• Nils Marsch,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2015, 11, 1700–1706, doi:10.3762/bjoc.11.184

• , confirming its antimicrobial activity. The E-configuration of the chloroalkene moiety of indiacen B was confirmed by X-ray analysis. Keywords: biological evaluation; heterocycles; indoles; natural products; total synthesis; Introduction Indole alkaloids prenylated at the benzene ring are found in tropical

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• substrates. Consequently, the Gibbs energy of the homodesmic reaction (ΔGr,sol) and the pKa value are related by the following equation: Biological evaluation. The antiproliferative activity of N-arylated pyrrole and indole derivatives was studied in the A2058 (ATCC® CRL-11147) cell line as described

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• µL, 67.5 µM) were passed through the binding assay column allowing quick determinations of their HSA binding affinity. This proof of concept study therefore marks one of the first published reports where flow chemical synthesis is combined with direct biological evaluation of new structures thus

C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope

• Manuel Johannes,
• Maximilian Reindl,
• Bastian Gerlitzki,
• Edgar Schmitt and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2015, 11, 155–161, doi:10.3762/bjoc.11.15

• , 16, 17, 18a, 18b, 19, 20, protocols of biological evaluation and copies of NMR spectra of compounds 8, 9, 10, 16, 17. Acknowledgements Support from the Deutsche Forschungsgemeinschaft DFG (HO 2563/1-2) and the Excellence Cluster Center of Integrated Protein Science Munich (CIPSM) is gratefully

Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase

• María Emilia Cano,
• Rosalía Agusti,
• Alejandro J. Cagnoni,
• María Florencia Tesoriero,
• José Kovensky,
• María Laura Uhrig and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 3073–3086, doi:10.3762/bjoc.10.324

• -acetyllactosamine was also evaluated. Results and Discussion As part of our project on the synthesis and biological evaluation of multivalent ligands, two families of mono- and divalent structures were synthesized in order to study their ability as acceptors or inhibitors of the reaction catalyzed by the T. cruzi

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• also highlight new technologies and techniques applied to this area of electrosynthesis. We conclude with the use of this electrosynthetic approach to challenging syntheses of natural products and other complex structures for biological evaluation discussing recent technological developments in

Gold(I)-catalysed synthesis of a furan analogue of thiamine pyrophosphate

• Amjid Iqbal,
• El-Habib Sahraoui and
• Finian J. Leeper

Beilstein J. Org. Chem. 2014, 10, 2580–2585, doi:10.3762/bjoc.10.270

• over the triazole analogues that it can be functionalised at the C-2 position. Conclusion In conclusion, we report here the short synthesis of a furan analogue of thiamine, which could be diphosphorylated to give an analogue of ThDP. Biological evaluation of this diphosphate showed that it is 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

• compounds can be regarded as building blocks for further elaborations towards new analogues of AHLs. Therefore this study aimed towards the synthesis and biological evaluation of a series of novel halogenated analogues, in which a chlorine, bromine or iodine atom was introduced. To further evaluate the

• chlorinated AHL analogues 11a–f via reaction with S-homoserine lactone hydrobromide (1) and triethylamine (Scheme 3). Biological evaluation The above mentioned natural AHLs 3 and their halogenated analogues 6, 8 and 11 were first tested for their ability to induce fluorescence in the Escherichia coli JB523

• ), 2860 (CH), 2930 (CH), 2958 (CH), 3298 (NH); chromatography: EtOAc/PE 4:1 Rf 0.48; melting point: 144 °C; white powder; yield: 42%. Biological evaluation Escherichia coli JB523 green fluorescent protein (GFP) microplate assay Strain JB523 was grown overnight at 28 °C in Luria–Bertani (LB) medium

Synthesis and biological activity of N-substituted-tetrahydro-γ-carbolines containing peptide residues

• Nadezhda V. Sokolova,
• Valentine G. Nenajdenko,
• Vladimir B. Sokolov,
• Daria V. Vinogradova,
• Elena F. Shevtsova,
• Ludmila G. Dubova and
• Sergey O. Bachurin

Beilstein J. Org. Chem. 2014, 10, 155–162, doi:10.3762/bjoc.10.13

• significant influence on mitochondrial swelling (data not shown). But at higher pharmacologically relevant concentration of 30 µM (60 nmol/mg mitochondria) all compounds did not affect the ΔΨm and increased the resistance of mitochondria to calcium-induced MPT (Table 2). The results of biological evaluation

Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

• John Li,
• May May Leong,
• Alastair Stewart and
• Mark A. Rizzacasa

Beilstein J. Org. Chem. 2013, 9, 2762–2766, doi:10.3762/bjoc.9.310

• ][17] and E3 [18] with full experimental details included for resolvins D3 [11], E2 [16] and E3 [18]. An improved synthesis of the C16–C20 fragment of resolvin E1 has also been reported [19]. We were interested in accessing amounts of RvD2 (1) for biological evaluation but without detailed synthetic

• sequence to follow and given the very high cost [20] of commercial 1 we elected to develop an alternative route to provide this important compound and analogues for further biological evaluation. Herein we describe a synthesis of RvD2 (1) which includes full experimental details so that other researchers

• RvD2 (1) has been completed using a common linchpin Wittig reaction. Using this approach, we were able to prepare sufficient quantities of this important inflammation resolving compound for further biological evaluation. Structures of resolvins D1 (1) and D2 (2). Retrosynthetic analysis of RvD2 (1