α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA

• Shital K. Chattopadhyay,
• Subhankar Ghosh,
• Sarita Sarkar and
• Kakali Bhadra

Beilstein J. Org. Chem. 2019, 15, 2524–2533, doi:10.3762/bjoc.15.245

• useful level of bioactivity, α,ß-didehydro SAHA derivatives remain to be explored, to the best of our knowledge. Herein, we disclose two alternative synthetic routes to SAHA and preliminary biological evaluation of some α,ß-didehydro derivatives of SAHA. Results and Discussion Our synthesis of SAHA and α

• . Preliminary biological evaluation of three such analogues involving the measurement of GI50 values against Hela cells and ROS-mediated apoptosis as possible mechanism of action of these analogues, have shown that the data obtained for one compound (11b) are very close to those of SAHA for the cell line

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• photoswitchable diazeno compound 11 was subjected to biological evaluation to test the effect of photoisomerization on the inhibitory activity. The enzyme assay mixture containing 11 was exposed to 5 minutes of 365 nm radiation and compared with the results of a non-irradiated measurement. The applied radiation

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• present the design, synthesis and biological evaluation of novel mannosylated desmuramyl peptide derivatives. Mannose was coupled to dipeptides containing a lipophilic adamantane on N- or C-terminus through a glycolyl or hydroxyisobutyryl linker. Adjuvant activities of synthesized compounds were

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• core structure, 1 only has one stereocenter as compared to seven in AbC. Furthermore, the benzylated derivative 2 was also envisioned to mimic the favorable toxicity profile observed for atrop-O-benzyl-desmethyl-abyssomicin C (Figure 1) [10]. Here we present the synthesis and biological evaluation of 1

• targeted compounds 1 and 2 in 17% and 30% yield over the two steps, respectively. For the final step, several oxidation agents were evaluated, and the highest yields were achieved with Dess–Martin periodinane, which converted 22 and 23 to 1 and 2 in 24% and 41% yield, respectively. Biological evaluation

• Supporting Information File 102: Experimental part (modelling and docking, synthesis and biological evaluation), and copies of NMR spectra. Acknowledgements The Olle Engkvist Byggmästare foundation, the Centre for Antibiotic Resistance Research at the University of Gothenburg (CARe) and the Swedish Research

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• position is reported. These model compounds, never described before in literature, allowed to perform a preliminary biological evaluation as well as an evaluation of their stability. The compatibility of boronic acids/esters in the presence of other functional groups has been reviewed [8]. Usually, β

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• conjugation [62][63]. Cytotoxic spirostan saponins were chosen as model compounds for the preparation of Ugi-derived analogues, such as 55 and 56 suitable for biological evaluation [62]. Besides the glucose unit, other trisaccharidic moieties (e.g., β-chacotrioside) could also be conjugated to functionalized

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• solution inevitably cause the disruption of the supramolecular assembly [23]. Analyses under saline stress were not performed as the ultimate aim is to use of those OMV models under physiological conditions. Biological evaluation of the synthesized compounds Competitive enzyme-linked lectin assays (ELLA

Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

• Constantinos G. Neochoritis,
• Maryam Kazemi Miraki,
• Eman M. M. Abdelraheem,
• Ewa Surmiak,
• Tryfon Zarganes-Tzitzikas,
• Beata Łabuzek,
• Tad A. Holak and
• Alexander Dömling

Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45

• relatively good yields (29–60%). 16 different indole-based macrocycles were synthesized with their size varying from 11–13, 15, 17 and 19 atoms (Scheme 3). Biological evaluation Our previously introduced three-point pharmacophore model on mimicking the hot triad (Phe19, Trp23 and Leu26, F19W23L26) was the

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• ]. Since then, HPA-12 has been the subject of extensive biological evaluation. The HPA-12-mediated CERT knockdown has been associated with restoration of cell death in paclitaxel-resistant ovarian cancer cells [3] and also with the increased rate of ceramide-induced apoptosis following UVB irradiation

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• . Moreover, the O-to-N replacement is expected to increase solubility and possible polar interactions with the target. In this work we report the design, synthesis and biological evaluation of a number of pyrrolidine-based hamamelitannin analogues. The envisioned strategy for the synthesis of the target

• which the cationic character of the pyrrolidine nitrogen is removed, were also synthesized. The correct stereochemistry of the synthesized analogues was unequivocally proven via X-ray structural analysis of compound 3a (Figure 2). Biological evaluation The synthesized analogues were tested in a S

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• , the current process is mild enough to be applied on a broad range of functional groups. Further studies on the application of this reaction with broader substrate scope as well as the biological evaluation of the synthesized pyridines are in progress which will be documented in due course of time

Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• primary amines 12, which following metal-catalysed cyclisation would give 1,2-disubstituted quinolones 14. Upon the successful synthesis of analogues of the form 14, biological evaluation of these and the natural products 1, 4 and 5–7 (synthesised during our previous study [11]) would then be possible. In

The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• chelating groups of the siderophore. The synthesis is readily amenable to the preparation of analogues whereby the siderophore component of the conjugate can be modified. The route will be used to prepare a library of siderophore–phenothiazine conjugates for full biological evaluation of much needed new

• Supporting Information File 328: Full experiential protocols, characterisation of compounds including 1H and 13C NMR spectra, and biological evaluation of compound 4. Acknowledgements We thank the Royal Society for funding this research. We would also like to acknowledge Mick Lee for HRMS data of final

• number of techniques where investigated for purification including standard chromatography, recrystallization and trituration as the crude 1H NMR revealed the majority of the desired product. However, purification by semi-preparative HPLC was required to obtain analytically pure material for biological

Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase

• Nisachon Khunnawutmanotham,
• Cherdchai Laongthipparos,
• Patchreenart Saparpakorn,
• Nitirat Chimnoi and
• Supanna Techasakul

Beilstein J. Org. Chem. 2018, 14, 2545–2552, doi:10.3762/bjoc.14.231

• that may be useful for binding with this enzyme. Herein, we report our progress on the synthesis, biological evaluation, and molecular docking of 3-aminocoumarin linked with the benzylpyridinium moiety through an amide bond. Results and Discussion Chemistry The target 3-aminocoumarin-N-benzylpyridinium

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• potential for chemotherapy. Since targeted therapy provides new perspectives for treatment of cancer, new potent analogues of cytotoxic agents containing functional groups for conjugation to homing devices are required. We describe the design, synthesis and biological evaluation of three new unit B

• column chromatography. The allyl ether in 23 was cleaved using Pd(PPh3)4 as Pd(0) source and phenylsilane as scavenger to obtain the cryptophycin analogue 24 in good purity. Biological evaluation The biological activity of the modified unit B analogues was determined in a cell viability assay using the

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• yields that made biological evaluation impossible. Consequently, for about ten years, research in the field of carboxyesterase-responsive ONs protected at the phosphate backbone had waned until Dowdy reported on the synthesis, delivery and in vivo activity of siRNA prodrugs containing charge-neutralizing

• linkage (Scheme 14) [59]. Consequently, the presence of only one phosphate monoester function in an fma ON significantly increased the solubility. Unfortunately, no biological evaluation of such modified ONs was performed, and only the complete conversion of modified CpG into unmodified CpG upon elevated

Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting

• Lizeth Bodero,
• Paula López Rivas,
• Barbara Korsak,
• Torsten Hechler,
• Andreas Pahl,
• Christoph Müller,
• Daniela Arosio,
• Luca Pignataro,
• Cesare Gennari and
• Umberto Piarulli

Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29

• = 9.9), especially when compared to the strictly related cyclo[DKP-RGD]-Val-Ala-PTX conjugate 5 (TI = 2.4) [30]. Results and Discussion In the present paper, we report the synthesis and biological evaluation of two cyclo[DKP-RGD]-α-amanitin and three cyclo[DKP-isoDGR]-α-amanitin conjugates. In these

Synthesis of fluoro-functionalized diaryl-λ³-iodonium salts and their cytotoxicity against human lymphoma U937 cells

• Prajwalita Das,
• Etsuko Tokunaga,
• Hidehiko Akiyama,
• Hiroki Doi,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24

• biological evaluation, this is the first report to highlight the cytotoxicity of diaryliodonium salts against U937 cells. Since diaryliodonium salts are fundamentally oxidizing agents, there might be a stronger correlation between cytotoxicity and the oxidation potential of these salts. We will continue the

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

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