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

• Yong-Chul Jeong Mark G. Moloney Chemistry Research Laboratory, University of Oxford, Mansfield Rd, University of Oxford, OX1 3TA, UK 10.3762/bjoc.9.224 Abstract A chemical library of carboxamide-substituted tetramates designed by analogy with antibacterial natural products, a method for their

• inhibitory activity) [7] and unnatural systems, such as 3-carboxamide tetramic acid 1c and 3-carboxamide piperidine-2,4-dione 1d (undecaprenyl pyrophosphate synthase (UPPS) inhibitory activity) [8] exhibit high levels of antibacterial activity (Figure 1). All these systems share a β-dicarbonyl core. A drug

• discovery programme inspired by these natural products, as promoted by Waldmann [9], was of interest to us. We have recently focused on the construction and evaluation of libraries derived from tetramic acid scaffolds and discovered that bicyclic 3-carboxamide 1e, bicyclic 3-acyl 1f and monocyclic 3-acyl 1g

A Lewis acid-promoted Pinner reaction

• Dominik Pfaff,
• Gregor Nemecek and
• Joachim Podlech

Beilstein J. Org. Chem. 2013, 9, 1572–1577, doi:10.3762/bjoc.9.179

• used. A possible mechanism of this reaction is given in Scheme 7. Double silylation leads to the formation of a good leaving group and the highly electrophilic benzylic carbon is attacked by the nitrile yielding a nitrilium cation. The reaction is finalized by hydrolysis furnishing the carboxamide

• acid-promoted Pinner reaction. Synthesis of monaspilosin. Proposed mechanism of the trimethylsilyl triflate-promoted Ritter reaction. Selection of optimization experiments. Variation of nitriles and alcohols.a Carboxamide formation in a Pinner-type reaction.a Supporting Information Supporting

Gold-catalyzed intermolecular hydroamination of allenes with sulfonamides

• Chen Zhang,
• Shao-Qiao Zhang,
• Hua-Jun Cai and
• Dong-Mei Cui

Beilstein J. Org. Chem. 2013, 9, 1045–1050, doi:10.3762/bjoc.9.117

• [7][8][9][10][11][12][13][14][15]. More recently, Au(I), Au(III), Pt(II) and Rh(I) have been used for the intermolecular hydroamination of allenes with secondary alkylamines, ammonia, or carboxamide [7][16][17][18][19][20][21][22][23][24]. Although some of these advances have been efficiently made in

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

• able to modulate dopamine receptors because of their ability to place the carboxamide NH2 pharmacophore in the same topological space as that seen in the type II β-turn. Extensive studies with the spiro-bicyclic PLG peptidomimetics also established that both positive and negative modes of modulation

• hexafluorophosphate (HATU) as the coupling reagent in order to provide the primary carboxamide intermediate, which could be deprotected to give 48. The lithium enolate of Seebach’s oxazolidinone 30 served as the starting material for the stereoselective synthesis of ethylene-linked biproline derivative 50. The nature

• the Φ, ψ, and ω torsion angles of the type II β-turn, the type VI β-turn, and the polyproline II helix conformational types indicates that they each possess similar torsion angles at their N-termini, but they differ at their C-termini. However, they all place the carboxamide NH2 pharmacophore in the

Chemical–biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target

• Jonathan W. Choy,
• Clifford Bryant,
• Claudia M. Calvet,
• Patricia S. Doyle,
• Shamila S. Gunatilleke,
• Siegfried S. F. Leung,
• Kenny K. H. Ang,
• Steven Chen,
• Jiri Gut,
• Juan A. Oses-Prieto,
• Jonathan B. Johnston,
• Michelle R. Arkin,
• Alma L. Burlingame,
• Jack Taunton,
• Matthew P. Jacobson,
• James M. McKerrow,
• Larissa M. Podust and
• Adam R. Renslo

Beilstein J. Org. Chem. 2013, 9, 15–25, doi:10.3762/bjoc.9.3

• )-1-(benzenesulfonyl)-5-phenylpent-1-en-3-yl]amino]-3-(4-methylphenyl)-1-oxopropan-2-yl]pyridine-4-carboxamide (4), which is trypanocidal at ten-fold lower concentrations than for 1. We now find that the trypanocidal activity of 4 derives primarily from the inhibition of T. cruzi 14-α-demethylase

Features of the behavior of 4-amino-5-carboxamido-1,2,3-triazole in multicomponent heterocyclizations with carbonyl compounds

• Eugene S. Gladkov,
• Katerina A. Gura,
• Svetlana M. Sirko,
• Sergey M. Desenko,
• Ulrich Groth and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2012, 8, 2100–2105, doi:10.3762/bjoc.8.236

• of the NH2-group and endocyclic NH (Figure 2, compound VII or its position isomer VIII), or an alternative pathway involving the NH2-group and carboxamide fragment [25][26] (compound IX). Thus, there are several alternative directions for reactions between 4-amino-5-carboxamido-1,2,3-triazole

• '-cyclopentane}-3-carboxamide (4a) or 5,6,7,8-tetrahydro-4H-spiro{[1,2,3]triazolo[5,1-b]quinazoline-9,1'-cyclohexane}-3-carboxamide (4b) under all the conditions tested. The best results were observed in the case of microwave-assisted synthesis in methanol at 120 °C. Spirocompound 4c may be obtained by a

Total synthesis and biological evaluation of fluorinated cryptophycins

• Christine Weiß,
• Tobias Bogner,
• Benedikt Sammet and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 2060–2066, doi:10.3762/bjoc.8.231

• homoallyl alcohol 16. The magnesium bromide diethyl etherate mediated allylation proceeded under substrate control and with complete diastereoselectivity [23][32]. Cross-metathesis of homoallyl alcohol 16 with the unit B derived acrylamide 17 provided the α,β-unsaturated δ-hydroxy carboxamide 18 (Scheme 2

• B was synthesized by the same convergent route as described for derivative 22. Homoallyl alcohol 27 [23] was reacted with the D-pentafluorophenylalanine derivative 26 in a cross-metathesis reaction in the presence of Grubbs II catalyst (Scheme 4). The resulting α,β-unsaturated δ-hydroxy carboxamide

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• -methyl-2-butene. Proposed mechanism of the N-indolyl prenylation. Regioselective arylation of indoles by dual C–H functionalization. Plausible mechanism of the selective indole arylation. Chemoselective cyclization of N-allyl-1H-indole-2-carboxamide derivatives. Intramolecular annulations of

An intramolecular inverse electron demand Diels–Alder approach to annulated α-carbolines

• Zhiyuan Ma,
• Feng Ni,
• Grace H. C. Woo,
• Sie-Mun Lo,
• Philip M. Roveto,
• Scott E. Schaus and
• John K. Snyder

Beilstein J. Org. Chem. 2012, 8, 829–840, doi:10.3762/bjoc.8.93

• dried over sodium sulfate, and then the solvent was removed in vacuo. The residue was purified by flash chromatography to yield the desired amide 13. Representative example: N-Methyl-5-[(4-methylbenzene)sulfonyl]-N-(prop-2-yn-1-yl)-5H-[1,2,4]triazino[5,6-b]indole-3-carboxamide (13a). According to

Aryl nitrile oxide cycloaddition reactions in the presence of pinacol boronic acid ester

• Sarah L. Harding,
• Sebastian M. Marcuccio and
• G. Paul Savage

Beilstein J. Org. Chem. 2012, 8, 606–612, doi:10.3762/bjoc.8.67

• -3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4,5-dihydroisoxazole-5-carboxamide (7d): Isolated as a colourless oil (85 mg, 49%) after purification by column chromatography (80% Et2O in petroleum ether, Rf 0.43, 50% Et2O in petroleum ether); 1H NMR (CDCl3, 400 MHz) δ 7.82 (d, J = 8.3 Hz

Synthesis and characterization of new diiodocoumarin derivatives with promising antimicrobial activities

• Hany M. Mohamed,
• Ashraf H. F. Abd EL-Wahab,
• Ahmed M. EL-Agrody,
• Ahmed H. Bedair,
• Fathy A. Eid,
• Mostafa M. Khafagy and
• Kamal A. Abd-EL-Rehem

Beilstein J. Org. Chem. 2011, 7, 1688–1696, doi:10.3762/bjoc.7.199

• with p-phenylenediamine in boiling AcOH afforded the 6,8-diiodocoumarin-3-carboxamide derivatives 4 and 5, respectively. Interaction of 3 with glycine in dry benzene under reflux gave the new 6,8-diiodocoumarin-3-N,N-dimethylcarboxamide (7) instead of 6,8-diiodocoumarin-3-ylcarbonylglycine (6). The

• and p-aminophenylacetic acid), was successful, and the corresponding 6,8-diiodocoumarin-3-carboxamide derivatives 8–11 were obtained (Scheme 3). The structures of compounds 8–11 were established by IR, 1H NMR, 13C NMR and MS. The IR spectra of compound 8 showed 3287 cm–1 (OH, NH) and 1719 cm–1 (CO

• that the activity is considerably affected by the presence of the diiodocoumarino[3,4-c]pyridine, 2-methyl-8,10-diiodobenzo[2,1-g]-2H-1,3-oxazocine, diiodocoumarin-3-carboxamide or 2,3-dimethyl-8,10-diiodobenzo[2,1-g]-2H-1,3-oxazocine, and slightly decreases with the presence of different amide groups

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

• Cécile Verrier,
• Pierrik Lassalas,
• Laure Théveau,
• Guy Quéguiner,
• François Trécourt,
• Francis Marsais and
• Christophe Hoarau

Beilstein J. Org. Chem. 2011, 7, 1584–1601, doi:10.3762/bjoc.7.187

• in favour of the C5 position (Scheme 16) [64]. Miura first highlighted the reactivity of the C4 position of the oxazole ring in a direct substitutive-coupling methodology by reacting N-phenyl-2-phenyloxazole-5-carboxamide with phenylbromide (Scheme 17) [65]. Nevertheless, the introduction of a phenyl

Access to pyrrolo-pyridines by gold-catalyzed hydroarylation of pyrroles tethered to terminal alkynes

• Elena Borsini,
• Gianluigi Broggini,
• Andrea Fasana,
• Chiara Baldassarri,
• Angelo M. Manzo and
• Alcide D. Perboni

Beilstein J. Org. Chem. 2011, 7, 1468–1474, doi:10.3762/bjoc.7.170

• either from direct cyclization or from a formal rearrangement of the carboxamide group. Terminal alkynes are essential to achieve bicyclic pyrrolo-fused pyridinones by a 6-exo-dig process, while the presence of a phenyl group at the C–C triple bond promotes the 7-endo-dig cyclization giving pyrrolo

• . Cyclization reactions of pyrrole-carboxamides A solution of the appropriate pyrrole-carboxamide (2 mmol) was stirred, under an argon atmosphere, with AuCl3 (0.01 mmol) in 30 mL of an appropriate solvent (see Table 3 and Table 4 for solvents, temperatures and times). At the end of the reaction, the solvent was

NMR studies of anion-induced conformational changes in diindolylureas and diindolylthioureas

• Damjan Makuc,
• Jennifer R. Hiscock,
• Mark E. Light,
• Philip A. Gale and
• Janez Plavec

Beilstein J. Org. Chem. 2011, 7, 1205–1214, doi:10.3762/bjoc.7.140

• -indole-2-carboxamide (0.27 g, 1.07 mM) with 7-isothiocyanato-N-phenyl-1H-indole-2-carboxamide (0.31 g, 1.07 mM) in pyridine in 27% yield (see Supporting Information File 1 for details). Structural features and NMR chemical shifts The conformational properties of diindolylureas and diindolylthioureas 1–4

• are spatially close and the C2α carbonyl group is oriented towards the indole H1 proton. NOE enhancements between H2β and H3 protons were observed also in the 3·AcO− and 3·BzO− complexes, which suggests that the orientation of the carboxamide group along the C2–C2α bond is retained in 3 upon addition

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• as T-cells and macrophages followed by viral fusion and entry into white blood cells. Maraviroc blocks this pathway by acting as an antagonist for the CCR-5 receptor hence disrupting HIV life cycle. The structural features of this molecule are a geminal difluorocyclohexyl carboxamide which is linked

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• reviewed in two books published in 1964 [5] and in 1967 [6]. Structurally simple 5-amino-1-tert-butylpyrazole-4-carboxamide I was found to inhibit p56 Lck [7] (Figure 1). 5-Amino-1-(4-methylphenyl) pyrazole II has been tested as an NPY5 antagonist [8]. 5-Amino-4-benzoyl-3-methylthio-1-(2,4,6

• al. [71] have reported that the reaction of α-cyano-β-dimethylaminocrotonamide (103) with hydrazine hydrate yields 5-amino-3-methylpyrazole-4-carboxamide (104). The reaction proceeds by loss of dimethylamine in first step followed by cyclization via nucleophilic attack on cyano group (Scheme 29). 3

• -heteroaryl-3-methyl/aryl-4-cyanopyrazoles. Synthesis of 5-amino-3-methylpyrazole-4-carboxamide. Synthesis of 4-acylamino-3(5)-amino-5(3)-arylsulfanylpyrazoles. Synthesis of 5-amino-1-aryl-4-diethoxyphosphoryl-3-halomethylpyrazoles. Synthesis of substituted 5-amino-3-trifluoromethylpyrazoles 114 and 118

A new fluorescent chemosensor for fluoride anion based on a pyrrole–isoxazole derivative

• Zhipei Yang,
• Kai Zhang,
• Fangbin Gong,
• Shayu Li,
• Jun Chen,
• Jin Shi Ma,
• Lyubov N. Sobenina,
• Albina I. Mikhaleva,
• Guoqiang Yang and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2011, 7, 46–52, doi:10.3762/bjoc.7.8

• recognition and sensing purposes in aprotic solvents. We present here a new example of a receptor, 3-amino-5-(4,5,6,7-tetrahydro-1H-indol-2-yl)isoxazole-4-carboxamide (receptor 1), which contains pyrrole, amide and amino subunits. This receptor shows both changes in its UV–vis absorption and fluorescence

• advantageous to develop high-effective sensors that can detect fluoride anion in food and animal feed. In this work, we report a new fluoride receptor 1 (Figure 1), 3-amino-5-(4,5,6,7-tetrahydro-1H-indol-2-yl)isoxazole-4-carboxamide [9], which contains receptive groups toward anions and no urea/thiourea

Oxalyl retro-peptide gelators. Synthesis, gelation properties and stereochemical effects

• Janja Makarević,
• Milan Jokić,
• Leo Frkanec,
• Vesna Čaplar,
• Nataša Šijaković Vujičić and
• Mladen Žinić

Beilstein J. Org. Chem. 2010, 6, 945–959, doi:10.3762/bjoc.6.106

• carboxylic acid, methyl ester and carboxamide, namely (S,S)-bis(LeuLeu) 1a, b, c; (S,S)-bis(PhgPhg) 3a, b, c and (S,S)-bis(PhePhe) 5a, b, c and, the second containing two different amino acids, (S,S)-bis(LeuPhg) 2a, b, c and (S,S)-bis(PhgLeu) 4a, b, c (configurations of only two of the four stereogenic

• additional examples that some racemates could be more effective gelators of specific solvents than the pure enantiomers; (iii) among the terminal carboxamide gelators the heterochiral (S,R)-1c diastereoisomer is capable of immobilizing up to 10 and 4 times larger volumes of dichloromethane and toluene

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

An enantiomerically pure siderophore type ligand for the diastereoselective 1 : 1 complexation of lanthanide(III) ions

• Markus Albrecht,
• Olga Osetska,
• Thomas Abel,
• Gebhard Haberhauer and
• Eva Ziegler

Beilstein J. Org. Chem. 2009, 5, No. 78, doi:10.3762/bjoc.5.78

• -carboxamide) 1a-H3 The ether 4 (0.18 g, 0.13 mmol) was placed in a Schlenk flask. The rearrangement proceeded at 165 °C under dry inert atmosphere of N2. The dark brown residue was purified by a short silica column (EtOAc, Rf = 0.26) to furnish a bright brown solid. Yield: 0.16 g (90 %); mp 189–196 °C. 1H NMR

• (m), 848 (s), 809 (w), 774 (m), 723 (m), 662 (w). HRMS (ESI): calcd. for C81H99N15O9 [M + Na]+: m/z = 1448.7619; found 1448.7637. Synthesis and characterization of a mononuclear lanthanum(III) complex with cyclohexapeptide based tris(N,N-diethyl-8-hydroxyquinoline-2-carboxamide) [(1a)La] LaCl3 · 7

Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity

• Nisachon Khunnawutmanotham,
• Nitirat Chimnoi,
• Arunee Thitithanyanont,
• Patchreenart Saparpakorn,
• Kiattawee Choowongkomon,
• Pornpan Pungpo,
• Supa Hannongbua and
• Supanna Techasakul

Beilstein J. Org. Chem. 2009, 5, No. 36, doi:10.3762/bjoc.5.36

• . Then amine 27 and the acid 30 underwent coupling to produce carboxamide 31. Diazepinone ring closure was performed by heating 31 in hexamethyldisilazane. Afterwards, the nitro group was reduced to produce the hydrochloride salt 10. Treatment of 10 with 50% aqueous NaOH yielded its corresponding free

Synthesis of rigidified flavin–guanidinium ion conjugates and investigation of their photocatalytic properties

• Harald Schmaderer,
• Mouchumi Bhuyan and
• Burkhard König

Beilstein J. Org. Chem. 2009, 5, No. 26, doi:10.3762/bjoc.5.26

• -dihydrobenzo[g]pteridin-10(2H)-yl]ethyl}-3-azabicyclo[3.3.1]nonane-7-carboxamide; Flavin-Boc-guanidin 7 To a solution of HOBt·H2O (89 mg, 580 μmol), EDC (90 mg, 580 μmol) and DIPEA (171 μL, 970 μmol) in CH2Cl2 (6.5 mL) were added compound 6 (252 mg, 480 μmol) and mono Boc-protected guanidine (86 mg, 530 μmol

• -7-carboxamide; Flavin-Boc-guanidin 10 To a solution of HOBt·H2O (226 mg, 1.67 mmol), EDC (226 mg, 1.45 mmol) and DIPEA (498 μL, 970 μmol) in CHCl3 (10 mL) was added compound 9 (548 mg, 969 μmol) and mono Boc-protected guanidine (231 mg, 1.45 mmol) at 0 °C. The mixture was stirred at room temperature

• -azabicyclo[3.3.1]nonane-7-carboxamide; Flavin-guanidinium 1 Compound 7 (210 mg, 317 μmol) was dissolved in CHCl3 (25 mL) and hydrogen chloride saturated diethyl ether (3 mL) was added dropwise. After stirring for 24 h, the solution was evaporated to 5 mL and diethyl ether (15 mL) was added to precipitate the

Synthesis of (S)-1-(2-chloroacetyl)pyrrolidine- 2-carbonitrile: A key intermediate for dipeptidyl peptidase IV inhibitors

• Santosh K. Singh,
• Narendra Manne and
• Manojit Pal

Beilstein J. Org. Chem. 2008, 4, No. 20, doi:10.3762/bjoc.4.20

• , 166.1, 166.4, 174.8, 174.9; m/z 192.1 [M+1]; Anal. Calcd for C7H10ClNO3: C, 43.88; H, 5.26; N, 7.31. Found: C, 43.25; H, 4.91; N, 6.98. Preparation of (S) 1-(2-chloroacetyl)pyrrolidine-2-carboxamide (9) To a solution of compound 8 (10.0 g, 0.052 mol) in dichloromethane (200 mL) was added slowly a