Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

• Leon Buschbeck,
• Aleksandra Markovic,
• Gunther Wittstock and
• Jens Christoffers

Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96

• (compound 2). If the Boc group is replaced by the slightly more electron-withdrawing carboxamide as in compound 3, this bathochromic shift (compared to compound 1) is only ca. 10 nm. Without an N-acceptor moiety, i.e., N-monoalkyl (compounds 4 and 5) or N,N'-dialkyl substitution (compounds 6–8), a stronger

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• antibacterial and antiviral. The presence of a carboxamide unit connected to carbon C-3 of the 4-oxoquinoline core has been associated with various biological activities. Experimentally, the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide occurs at the nitrogen of the oxoquinoline

• group, in a regiosselective way. In this work, we employed DFT methods to investigate the regiosselective ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide, evaluating its acid/base behavior and possible reaction paths. Keywords: alkylation; carboxamide; oxoquinoline; quinolone

• been explored and were successfully described by researchers around the world [3][4], such as antiviral [5][6], antiplasmoidal [7][8], anticancer [9][10], and trypanocide [11] activities. 4-Oxoquinoline-3-carboxamide derivatives, more specifically, have shown to be a promising structural scaffold for

Thermophilic phosphoribosyltransferases Thermus thermophilus HB27 in nucleotide synthesis

• Ilja V. Fateev,
• Ekaterina V. Sinitsina,
• Aiguzel U. Bikanasova,
• Maria A. Kostromina,
• Elena S. Tuzova,
• Larisa V. Esipova,
• Tatiana I. Muravyova,
• Alexei L. Kayushin,
• Irina D. Konstantinova and
• Roman S. Esipov

Beilstein J. Org. Chem. 2018, 14, 3098–3105, doi:10.3762/bjoc.14.289

• APRT limits the number of possible nucleotides that can be synthesized. Thus, for Thermus thermophilus HB27 APRT (TthAPRT), nucleotide synthesis is limited to the closest structural homologs of adenine (Table 1) [1]. Unfortunately, 1,2,4-triazole-3-carboxamide, its analogues, guanine, hypoxanthine, and

• phosphoribosyltransferase only [2]. Unfortunately, we did not find any product in reactions with compounds based on 1,2,4-triazole-3-carboxamide, which was also observed for E. сoli HPRT [15][16]. However, allopurinol and 8-azaguanine are substrates for TthHPRT, and 2-chloroadenine is a substrate for TthAPRT. For 2

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• protein [79]. Indicated key interactions are π-stacking of Y258 with the phenoxy moiety in the tail region and a hydrogen bond formed between the Q194 side chain and the carboxamide in the linker area. Furthermore the benzimidazole core shows hydrophobic contacts with isoleucins 149 and 236. More

• benzimidazole moiety (compound not shown) [80]. In a follow-up patent they generated PqsR inhibitor 45 as a front-runner compound [81], in which the benzimidazole headgroup was replaced by a substituted naphthalene bearing a carboxamide, in analogy to a fragment 44 of Zender et al. [82] and similar to the

• carboxamide-decorated nitro-quinoline scaffold described by Lu et al. (Figure 20) [73]. Compound 45 was highly potent in inhibiting pyocyanin production (stated IC50 in a range of 50–250 nM) and was furthermore able to suppress PQS and HHQ production (50 nM < IC50 < 250 nM). In a murine thigh infection model

Carbonylonium ions: the onium ions of the carbonyl group

• Daniel Blanco-Ania and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2018, 14, 2568–2571, doi:10.3762/bjoc.14.233

• , protonated carboxylic acids and esters (6; Figure 2), in agreement with other terms like “carboxy”, “carboxylic”, “carboxylate” and “carboxamide”. To augment confusion, other researchers have used this term to describe “oxycarbenium ions” 2 [32][33]. Carbonylonium ions: aldehydium and ketonium ions We

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• respect to the parent drug, e.g., temozolomide converted to 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC) [9]. 4) Excretion is the final step and is responsible for the removal of the parent drug and/or its metabolites from the human body. Renal excretion is the predominant route of elimination

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• triphosphates they inhibit the NS5B polymerase as did the triphosphates of the guanosine analogues [71]. The library of adenosine analogues was further expanded by introducing functional groups at C7 (16–19), which exhibit potent activity in RNA replication assays, with the carboxamide group in particular

Synthesis and stability of strongly acidic benzamide derivatives

• Frederik Diness,
• Niels J. Bjerrum and
• Mikael Begtrup

Beilstein J. Org. Chem. 2018, 14, 523–530, doi:10.3762/bjoc.14.38

• ; found, 434.0006. 4'-Methoxy-N-((trifluoromethyl)sulfonyl)-[1,1'-biphenyl]-4-carboxamide (15): Palladium(II) acetate (6 mg, 27 μmol), triphenylphosphine (20 mg, 76 μmol) and H2O (0.5 μL, 28 μmol) were mixed in degassed dimethylacetamide (1.0 mL). The catalyst was preformed by heating the mixture in a

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• -amines 198 possessing 4-(1H-benzimidazol-2-yl)phenylamine moiety at C4 position and primary as well as secondary amines at C6 position starting from 5-aminopyrazole-4-carboxamide (194). Compound 194 was treated with urea to give 1H-pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-dione (195) followed by chlorination

• 200 from the cyclocondensation of 5-amino-1-(2,4-dinitrophenyl)-1H-pyrazole-4-carboxamide (199) with aromatic aldehydes in the presence of iodine in acetonitrile (Scheme 55). The synthesized pyrazolo[3,4-d]pyrimidines were evaluated for antibacterial activities. Venkatesan et al. [132] also used 4

• -carboxamide-5-aminopyrazole 199 for the synthesis of pyrazolo[3,4-d]pyrimidines 207 (Scheme 56). The condensation of 199 with benzoyl isothiocyanate under reflux conditions in dry acetone provided benzoylthioureido derivatives 201 which were converted to methylthio derivative 202 with iodomethane in aqueous

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• followed a general procedure to access to (2S,3S)-CF3-threonine through an aldol reaction of CF3CHO with the Ni(II) complex of the chiral Schiff base of glycine which was introduced by Belokon et al. [23][24]. The chiral auxiliary (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamide (11) was obtained

Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• + calcd for C16H16N2O5, 316.3086; found, 316.1051. (S)-N-(2,4-Bis((E)-3,3,3-trifluoroprop-1-en-1-yl)phenyl)-1-(2-(1,3-dioxo-2H-isoindolin-2-yl)acetyl)pyrrolidine-2-carboxamide (7): 5 (2 mmol) and lithium hydroxide (12 mmol) were placed in a flask. To the flask was added THF (4.8 mL), methanol (1.5 mL

• residue was purified by column chromatography to give (S)-N-(2,4-bis((E)-3,3,3-trifluoroprop-1-en-1-yl)phenyl)-1-(2-(1,3-dioxo-2H-isoindolin-2-yl)acetyl)pyrrolidine-2-carboxamide (7) in 31% yield (71.9 mg, 0.12 mmol). A white solid: mp 181–182 °C; 1H NMR (CDCl3) δ 1.87–1.97 (m, 1H), 2.14–2.28 (m, 2H

• = 2.2, 6.4 Hz, 3F); MS m/z: M+ 565, 468, 285, 257, 188, 160; HRMS m/z: M+ calcd for C27H21F6N3O4, 565.1436; found, 595.1437. N-(S)-1-(2-Aminoacetyl)-N-(2,4-bis((E)-3,3,3-trifluoroprop-1-en-1-yl)phenyl)pyrrolidine-2-carboxamide (H-Gly-Pro-1): To solution of 7 (0.05 mmol) in ethanol was added hydrazine

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• propargylamines without an acidifying Cα-substituent. Synthesis of propargylamines containing polar or acidic functional groups The synthesis of propargylamines with polar substituents to mimic polar amino acids such as serine (alcohol), cysteine (thiol) or glutamine (carboxamide) requires special protective

• groups (Table 3). The cyano moiety was used as precursor of the carboxamide moiety of glutamine, since the cyano group is stable in the presence of nucleophiles and strong bases. The synthesis started with the Kolbe nitrile synthesis of 4-iodobutan-1-ol with NaCN. Performing this transformation in DMSO

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• from 1-iodoisoquinolines 8a–c. Synthesis of the alkaloids 6-O-demethylmenisporphine (4), dauriporphinoline (5), and bianfugecine (6). Attempted synthesis of bianfugecine (6) via directed remote metalation and subsequent trapping of the carboxamide group. Outcome of a D2O quenching experiment after

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• -binucleophile, acid – catalyst). Literature data indicate [14][25][59][97][98][99][100][101] that 5-aminopyrazoles bearing in the fourth position electron-withdrawing substituents like carboxamide, carboxylate or a carbonitrile group, posses chemical properties being different from other 5-aminopyrazoles but

• sometimes similar to 3-amino-1,2,4-triazole that was described as a component of GBB-3CR earlier [71][72][73][74][75]. Therefore, the first type of aminoazoles studied in our work was 5-amino-N-aryl-1H-pyrazole-4-carboxamide that showed 1,3-binucleophile properties in the condensation with aromatic

• -pyrazole-4-carboxamide (2b), methyl benzaldehyde-4-carboxylate (1f) and tert-butylisocyanide (3a, Table 2). Obviously, this reaction requires a longer reaction time (min. 48 h) and a moderate temperature (not more than 85 °C) to avoid tarring. Thus, after 48 h of heating (oil bath) at 85 °C the starting

Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates

• Anna Wrona-Piotrowicz,
• Marzena Witalewska,
• Janusz Zakrzewski and
• Anna Makal

Beilstein J. Org. Chem. 2017, 13, 1032–1038, doi:10.3762/bjoc.13.102

• evaporated. The products were isolated by flash chromatography (eluent: CH2Cl2). 2,7-Di-tert-butyl-N-ethylpyrene-1-carboxamide (3a). White solid (293 mg, 76%). Mp 258–259 °C; 1H NMR (600 MHz, CDCl3) δ 8.26 (s, 1H), 8.20 (d, J = 1.8 Hz, 1H), 8.18 (d, J = 1.8 Hz, 1H), 8.03 (m, 3H), 7.98 (d, J = 9.0 Hz, 1H

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• catalytic hydrogenolysis. The latter reaction simultaneously cleaves the benzyl and isopropylidene groups affording compound 2 as a single isomer [22]. In the case of 5-(2’-deoxy-2’-methyl-2’-fluoro-β-D-ribosyl)-1,2,3-triazole-4-carboxamide (3) the synthesis was more delicate as it is necessary to

• procedures for compounds 2, 5–7, and 10–18 are covered by the Ph.D. thesis of Fanny Cosson [22]. 5-(2’-C-Methyl-β-D-ribofuranosyl)-1,2,3-triazole-4-carboxamide (2) [22]: Through the solution of compound 7 (mixture of 7a and 7b, 0.49 g, 1.1 mmol) in anhydrous methanol (14 mL) was bubbled ammonia gas for 2 h

• at 0 °C. Then the mixture was stirred for 12 h at rt and concentrated in vacuum. The residue was purified by flash chromatography (EtOAc/cyclohexane, 3:7 to 1:0) affording the mixture of the corresponding 1-benzyl-4-(2’,3’-O-isopropylidene-2’-C-methyl-β-D-ribofuranosyl)-1,2,3-triazole-5-carboxamide

Characterization of the synthetic cannabinoid MDMB-CHMCZCA

• Carina Weber,
• Stefan Pusch,
• Dieter Schollmeyer,
• Sascha Münster-Müller,
• Michael Pütz and
• Till Opatz

Beilstein J. Org. Chem. 2016, 12, 2808–2815, doi:10.3762/bjoc.12.279

• legislation in 17 of the 30 member states of the EMCDDA [8]. It contains an N-alkylated indole core structure with carboxamide substituent in C-3 position, linked to an tert-leucine methyl ester and in previous studies, the amino acid was shown to be S-configurated [9]. Lately, the new synthetic cannabinoid

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

• ]-4'-carboxamide (6e): Yellow oil (Yield: 52 mg, 38%); IR (neat) νmax: 1705, 1686, 1628 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.71–7.67 (m, 1H), 7.62–7.26 (m, 8H), 4.17 (d, J = 12.7 Hz, 1H), 4.10–4.03 (m, 1H), 3.99 (d, J = 12.7 Hz, 1H), 3.88–3.79 (m, 1H), 3.74–3.66 (m, 1H), 3.62–3.54 (m, 1H), 3.54–3.40 (m

Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

• Vladimir A. Stepchenko,
• Anatoly I. Miroshnikov,
• Frank Seela and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2016, 12, 2588–2601, doi:10.3762/bjoc.12.254

• ) and the role of some amino acid residues of the catalytic site was characterized by the single-site mutagenesis [41]. It was suggested that the uracil binding site includes Gln166, the carboxamide group of which forms two strong hydrogen bonds 3N(H)···(O=)C(R)-NH2···(O=)C-2. Moreover, the carbonyl

Diastereoselective synthesis of 3,4-dihydro-2H-pyran-4-carboxamides through an unusual regiospecific quasi-hydrolysis of a cyano group

• Mikhail Yu. Ievlev,
• Oleg V. Ershov,
• Mikhail Yu. Belikov,
• Angelina G. Milovidova,
• Viktor A. Tafeenko and
• Oleg E. Nasakin

Beilstein J. Org. Chem. 2016, 12, 2093–2098, doi:10.3762/bjoc.12.198

• TCNE and ketones) with aldehydes in an acidic media. An unusual process of quasi hydrolysis of the cyano group was observed in the course of the described regio- and diastereoselective transformation. Keywords: diastereoselectivity; 3,4-dihydro-2H-pyran-4-carboxamide; nitriles; pyran; quasi-hydrolysis

• been recently described is the involvement of diazolactones in an inverse electron-demand Diels–Alder reaction [13]. At the same time the synthesis of 3,4-dihydro-2H-pyrans with a carboxamide group is a not sufficiently explored area. There is only one way to produce 3,4-dihydro-2H-pyran-4-carboxamides

• diastereoselective cascade reaction [23]. The crucial stage of the described transformation is the formation of a pyran-4-carboxamide intermediate. A trace amount of it was isolated accidentally and we could not repeat this procedure and characterize the compound by spectra. Results and Discussion In continuation of

A flow reactor setup for photochemistry of biphasic gas/liquid reactions

• Josef Schachtner,
• Patrick Bayer and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2016, 12, 1798–1811, doi:10.3762/bjoc.12.170

• convenience, reductive work-up with triphenylphosphine (PPh3) was performed to obtain the stable allyl alcohol derivative 3a which offers ample opportunities for chemical manipulations at the alcohol, alkene, and carboxamide functions. The choice of solvent is crucial as it determines the solubility of the

Synthesis of pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones: Rearrangement of pyrrolo[1,2-d][1,3,4]oxadiazines and regioselective intramolecular cyclization of 1,2-biscarbamoyl-substituted 1H-pyrroles

• Kkonnip Son and
• Seong Jun Park

Beilstein J. Org. Chem. 2016, 12, 1780–1787, doi:10.3762/bjoc.12.168

• of 3-chloro-1H-pyrrole-2-carboxylic acid (13) using the Vilsmeier reagent [9], followed by further amination to produce 1H-pyrrole-2-carboxamide 14 in good to excellent yield [9]. A reaction mixture of 14 with NaOH, NH4Cl, and NaClO led to the formation of the N-aminopyrrole 15 [11]. The addition of

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• as well as amino and carboxamide nucleophiles in lieu of a hydroxy group in 132 were accepted, yielding δ-lactam and glutarimide moieties, respectively [131][132]. When the B-domain of the rhiPKS was exchanged with an X-domain of glutarimide-producing PKS from the 9-methylstreptimidone PKS of S

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• -aminobutyric acid, Py – N-methylpyrrole carboxamide and Dp – N,N-dimethylaminopropylamine residues) was synthesized in the laboratory by solid-phase method [36][37] and used as a polyamide component. The first model is interesting for an anti-HIV strategy, but it is not suitable for visualization of dsDNA