Thiol-free chemoenzymatic synthesis of β-ketosulfides

• Adrián A. Heredia,
• Martín G. López-Vidal,
• Marcela Kurina-Sanz,
• Fabricio R. Bisogno and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2019, 15, 378–387, doi:10.3762/bjoc.15.34

• , substrates containing diversely substituted aryl moieties at the α-position of the enol ester, underwent smooth conversion (typically 94–99% except for p-nitrophenyl derivative 1f, for which more enzyme was needed to reach 96%, Table 2, entry 6), regardless the electronic nature of the substituents (see

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• ketone was converted to a trimethylsilyl enol ether upon treatment with KHMDS/Me3SiCl. By contrast, an electron-withdrawing p-nitrophenyl group was not tolerated because the intermediate cyclopropene 65i underwent decomposition under the reaction conditions of the Ireland–Claisen rearrangement

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• polysaccharide mannan, composed of linear α(1→6)-linked, and α(1→2)- and α(1→3)-branched mannopyranosides, and the glycoside p-nitrophenyl α-D-mannopyranoside showed even higher hemagglutination inhibitory potency. These initial experiments let to the assumptions that mycotin is a secreted D-arabinoside- and α-D

Non-native autoinducer analogs capable of modulating the SdiA quorum sensing receptor in Salmonella enterica serovar Typhimurium

• Matthew J. Styles and
• Helen E. Blackwell

Beilstein J. Org. Chem. 2018, 14, 2651–2664, doi:10.3762/bjoc.14.243

• as previously described [44][45][53][54][57][64] or purchased. Compounds 1, 2, 3 and A1 were purchased from Sigma-Aldrich. The E. coli reporter assay substrate, ortho-nitrophenyl-β-D-galactopyranoside (ONPG), was purchased from DOT Scientific. Stock solutions of compounds were prepared at 10 mM in

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• in this organ. In screening assays, 2-nitrophenyl galactoside (8) was identified displaying a dissociation constant of 10.6 µM (Figure 2). A detailed optimization program run by the Hultgren and Janetka groups yielded derivatives of N-acetyl galactosamine bearing biphenyl aglycons, such as compound 9

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• condensation position [48][49][50]. An exception to this is the recently reported synthesis of 3-(m-nitrophenyl)-5-nitro-3,4-dihydroquinazoline from m-nitroaniline and 1,3-dioxolane in the presence of strong protic acids [51]. In a related methodology, the ring closure of N-aryl-2-ABA is promoted by formic

• acid or other sources of C2 like ethyl orthoformate [52], diarylformamidines [53] or 1,1-dimethoxy-N,N-dimethylmethanamine [17]. Using an alternative approach, the corresponding 2-ABA was treated with acetic anhydride in concentrated sulfuric acid affording 2-methyl-6-nitro-3-(p-nitrophenyl)-3,4-DHQ

Revisiting ring-degenerate rearrangements of 1-substituted-4-imino-1,2,3-triazoles

• James T. Fletcher,
• Matthew D. Hanson,
• Joseph A. Christensen and
• Eric M. Villa

Beilstein J. Org. Chem. 2018, 14, 2098–2105, doi:10.3762/bjoc.14.184

• four imine products via a dynamic equilibrium of condensation, rearrangement and hydrolysis steps. Kinetic studies utilizing 1-(4-nitrophenyl)-1H-1,2,3-triazole-4-carbaldehyde with varying amines showed rearrangement rates sensitive to both steric and electronic factors. Such measurements were

• elevated temperature conditions. Surprisingly, triazole analogs with electron-withdrawing substituents underwent significant rearrangement even at room temperature. The spontaneous reactivity of 1-(4-nitrophenyl)-1H-1,2,3-triazole-4-carbaldehyde towards Dimroth rearrangement and its generation of a

• -(4-nitrophenyl)-1H-1,2,3-triazole-4-carbaldehyde may stand as a synthon of improved practical utility for preparing 1-substituted-4-formyl-1,2,3-triazole target compounds via this ring-degenerate rearrangement process. Such will be the target of future studies. Conversion of 1-substituted-4

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• . Consequently, α-D-mannopyranosides having an aromatic aglycon portion such as p-nitrophenyl α-D-mannopyranoside (1) and the squaric acid derivative 2 [19] (Figure 3) were identified as FimH ligands with relative high affinity (low μmolar range). Based on this knowledge, we proposed the three diazirine-labeled

• from p-nitrophenyl α-D-mannopyranoside (1), which was first reduced to the corresponding amine 6 [26][27] by catalytic hydrogenation (Scheme 1). HATU-mediated peptide coupling with Boc-protected glycine under basic conditions led to 7. After removal of the Boc protecting group using trifluoroacetic

• carbene after extrusion of nitrogen and a crosslinked product after insertion reaction; X = e.g., NH, O, CH2. FimH crystal structure (pdb code 1KLF) with docked p-nitrophenyl α-D-mannopyranoside (1, pNPMan). FimH is a two-domain protein comprising a lectin domain (FimHL) with the carbohydrate binding site

Defining the hydrophobic interactions that drive competence stimulating peptide (CSP)-ComD binding in Streptococcus pneumoniae

• Bimal Koirala,
• Robert A. Hillman,
• Erin K. Tiwold,
• Michael A. Bertucci and
• Yftah Tal-Gan

Beilstein J. Org. Chem. 2018, 14, 1769–1777, doi:10.3762/bjoc.14.151

• incubating the culture for 30 minutes at 37 °C with 20 µL of 0.1% Triton X-100. In a new plate, 100 µL of Z-buffer solution (60.2 mM Na2HPO4, 45.8 mM NaH2PO4, 10 mM KCl, and 1.0 mM MgSO4 in 18 MΩ H2O; pH was adjusted to 7.0 and the buffer was sterilized before use) containing 2-nitrophenyl-β-D

An amine protecting group deprotectable under nearly neutral oxidative conditions

• Shahien Shahsavari,
• Chase McNamara,
• Mark Sylvester,
• Emily Bromley,
• Savannah Joslin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2018, 14, 1750–1757, doi:10.3762/bjoc.14.149

• ; 13C NMR (100 MHz, CDCl3) δ 25.9, 27.4, 30.9, 61.0, 73.4 ppm; HRMS (ESI) m/z: [M + K]+ calcd for C7H14OS2K, 217.0123; found, 217.0121. 2-(1,3-Dithian-2-yl)propan-2-yl (4-nitrophenyl) carbonate (4): To a solution of 2-(1,3-dithian-2-yl)propan-2-ol (6.4 g, 36 mmol, 1 equiv) and pyridine (2.9 mL, 54 mmol

• –7.33 (m, 4H) ppm; 13C NMR (100 MHz, CDCl3) δ 24.6, 26.1, 31.1, 56.3, 85.3, 127.8, 128.2, 128.6, 138.7, 151.0 ppm; HRMS (ESI) m/z: [M + K]+ calcd for C14H19NO2S2K, 336.0754; found, 336.0760. 2-(1,3-Dithian-2-yl)propan-2-yl (4-nitrophenyl)carbamate (5f): Brown oil (37 mg, 42%); IR (thin film) ν 3305

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• the p-nitrophenyl ester method (Scheme 4, method A). The other one was described by Agrigento and co-workers, the cyclization was completed via the p-chlorophenyl thioester method with peptide-thioester being the precursor (Scheme 4, method B) [39]. Herein, we realized the synthesis of pseudostellarin

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• be used to analyze the content of samples withdrawn at suitable intervals. That is why many research groups prefer to use a simpler model, 2-hydroxypropyl p-nitrophenyl phosphate (HPNP; 1, Figure 5), the hydrolysis of which can be followed by UV-spectrophotometry. A lot of useful observations have

• attacking 2´-O−, the KIE is inverted, 16knuc/18knuc = 0.984 ± 0.004 [54]. Both effects are large and consistent with advanced P–O5´ fission and P–O2´ formation in the transition state. For comparison, with uridine 3´-(p-nitrophenyl phosphate), the leaving group KIE expectedly is small, 16klg/18klg = 1.0059

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• for the terminal galactose part of GM1 [37][38][39]. They screened a number of galactose derivatives with substitution at O1 and C2 and found that the most potent molecule in this library was m-nitrophenyl α-D-galactoside (4) which was 100 times better than galactose for binding to CTB [38][39]. In

• another report, Mitchell et al. designed and synthesised twenty 3,5-substituted phenylgalactosides, e.g., 5 and when these compounds were tested on CT it was found that they have a six-fold higher affinity than m-nitrophenyl α-D-galactopyranoside (Figure 4) [40]. Vrasidas et al. synthesised a simple

• exhibit binding affinity one order higher than m-nitrophenyl galactopyranoside (4) [48]. In another recent report, low molecular weight poly(N-acryloylmorpholine) was used to link galactose residues to form a bivalent inhibitor, but the biological assay demonstrated only moderate inhibitory activity [49

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

• , protected at O6 and O4 with a 2-(2-nitrophenyl)propyl (NPP) group, into siRNA (Scheme 20A) [81]. The most efficient siRNAs targeting EFGP expression in transfected HeLa cells were those modified in the central part of the siRNA – that is, in the nucleobases neighboring the argonaute cleavage site of mRNA

One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates

• Jun Ki Kim,
• Hwan Jung Lim,
• Kyung Chae Jeong and
• Seong Jun Park

Beilstein J. Org. Chem. 2018, 14, 243–252, doi:10.3762/bjoc.14.16

• compounds 7f and 7g, the low reactivity resulted from the decreased mesomeric effect of the furan structure: the higher electronegativity of oxygen facilitated the polarized form [71]. Among various arenes, the 4-nitrophenyl substituent 7p only afforded the desired thiophene 8p in a moderated yield (42

Transition-metal-free [3 + 3] annulation of indol-2-ylmethyl carbanions to nitroarenes. A novel synthesis of indolo[3,2-b]quinolines (quindolines)

• Michał Nowacki and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2018, 14, 194–202, doi:10.3762/bjoc.14.14

• ]. Several methods use prerequisite quinoline derivatives for the construction of the pyrrole ring of quindoline. 2-(2-Aminophenyl)-3-bromoquinoline cyclized to quindoline by reacting with pyridinium hydrochloride (d) [14]. Insertion of nitrene generated from 2-(2-nitrophenyl)quinoline by triethylphosphite

Synthesis and spectroscopic properties of β-meso directly linked porphyrin–corrole hybrid compounds

• Baris Temelli and
• Hilal Kalkan

Beilstein J. Org. Chem. 2018, 14, 187–193, doi:10.3762/bjoc.14.13

• with aldehydes [42]. When electron-withdrawing 4-nitrophenyl and pentafluorophenyl substituents were used on the dipyrromethane, hybrid compounds 4c and 4e were isolated in 16% and 20% yields, respectively. The synthesis of 4e with InCl3 afforded a very low yield, thus an equimolar amount of AlCl3 was

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

Binding abilities of polyaminocyclodextrins: polarimetric investigations and biological assays

• Marco Russo,
• Daniele La Corte,
• Annalisa Pisciotta,
• Serena Riela,
• Rosa Alduina and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2751–2763, doi:10.3762/bjoc.13.271

• slight excess (ca. 10%) of the proper amine in DMSO at 70 °C for 4 hours in the presence of Na2CO3 (1 equiv). The same procedure was adapted for the synthesis of guest 4. N-(4-Nitrophenyl)iminodiacetic acid disodium salt (4) Iminodiacetic acid (1.33 g, 10 mmol) was treated with an equimolar amount of

Binding abilities of a chiral calix[4]resorcinarene: a polarimetric investigation on a complex case of study

• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2698–2709, doi:10.3762/bjoc.13.268

• buried under those of the host, and cannot be identified). This indicates that the p-nitrophenyl group is allocated in the deshielding region provided by the aryl subunits of the host. Therefore, we can conclude that the aromatic moiety of the guest is specifically included into the cavity, in a quite

• macrocycle cavity. Consequently, the inclusion of the guest forces them in a conformation that is more exposed to the solvent bulk. Finally, taking back to the guest, the inclusion of its p-nitrophenyl group into the cavity implies that the aliphatic moiety protrudes out of the proline-decorated host rim

• subunit. The case of the imidazolium derivative 12 is intriguing, because in principle its 1:1 complex might involve the inclusion of either aromatic ring. However, the preferential inclusion of the p-nitrophenyl group may be reasonably presumed on the grounds of the fact that the complex formed by the

p-tert-Butylthiacalix[4]arenes functionalized by N-(4’-nitrophenyl)acetamide and N,N-diethylacetamide fragments: synthesis and binding of anionic guests

• Alena A. Vavilova and
• Ivan I. Stoikov

Beilstein J. Org. Chem. 2017, 13, 1940–1949, doi:10.3762/bjoc.13.188

• Alena A. Vavilova Ivan I. Stoikov Kazan Federal University, Kremlevskaya, 18, Kazan 420008, Russian Federation 10.3762/bjoc.13.188 Abstract New p-tert-butylthiacalix[4]arenes, which are mono-, 1,2-di- and tetrasubstituted at the lower rim containing N-(4’-nitrophenyl)acetamide and N,N

• receptors for F−, CH3CO2− and H2PO4− ions, which based on the synthesized thiacalix[4]arenes, have been obtained. It was shown that p-tert-butylthiacalix[4]arene tetrasubstituted at the lower rim by N-(4’-nitrophenyl)acetamide moieties bonded to the anions studied with association constants within the range

• receptor. In contrast to the 1,3-disubstituted macrocycle containing two N-(4’-nitrophenyl)acetamide moieties, the 1,2-disubstituted thiacalix[4]arene, which contains only one such fragment and a N,N-diethylacetamide moiety, selectively binds F− anions. Keywords: anion binding; synthesis; thiacalixarenes

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• in 1:1 ratios – were always formed, which is a serious drawback of this approach. Another well-known method based on retrosynthetic disconnections at the same C–C bond employed intramolecular vicarious nucleophilic substitution of hydrogen in the substituted N-(3-nitrophenyl)chloromethylsulfonamides

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• milling was performed at low temperatures (−30 °C) using an in-house ball mill equipped with a cooling jacket. As isothiocyanate component, liquid phenyl isothiocyanate and solid methyl, 1-naphthyl, 4-bromophenyl and 4-nitrophenyl isothiocyanates were screened. While ammonia, methylamine and dimethylamine

• next screened as catalysts in Morita–Baylis–Hillman reaction, and their performance matched the previously published catalytic activity. An analogous click-type reaction between 4-nitrophenyl isothiocyanate and trans-1,2-diaminocyclohexane quantitatively afforded enantiomeric (1R,2R)-10 and (1S,2S)-10

• one or two equivalents of phenyl, 4-methoxyphenyl, 4-chlorophenyl or 4-nitrophenyl isothiocyanate. In the 1:1 reaction, solvent-free mechanosynthesis selectively provided stable mono-thioureas 19a–d in ≥95% after 30 minutes (Scheme 6a). When the reactants were milled in a 1:2 ratio for 3 hours (9

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

• Juraj Dobiaš,
• Marek Ondruš,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2017, 13, 1350–1360, doi:10.3762/bjoc.13.132

• substituted o-phenylenediamine 11. Sakata et al. reported an interesting one-pot procedure yielding 6-substituted SYN quinoxalin-2(1H)-ones from substituted N-(2-nitrophenyl)-3-oxobutanamides [28]. Another example for preparation of the desired regioisomer starts from the nucleophilic substitution of o

Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• , 55.4, 51.6; IR (ATR): 2951, 2257, 1719, 1605, 1543, 1515, 1458, 1438, 1416, 1361, 1334, 1265, 1246, 1179, 1168, 1100, 1069, 1027, 948, 830, 735, 598, 583; HRMS: [M + H]+ calcd for C14H11NO2, 256.09682; found, 256.09730. Methyl 1-[(4-nitrophenyl)ethynyl]-1H-pyrrole-2-carboxylate (7b). To a solution of 1

• , 2920, 1670, 1605, 1510, 1473, 1373, 1341, 1242, 1176, 1021, 965, 830, 800, 736, 634, 595; HRMS: [M + H]+ calcd for C13H8INO2, 256.10805; found, 256.10860. 4-(4-Nitrobenzyl)pyrrolo[1,2-d][1,2,4]triazin-1(2H)-one (13b). Methyl 1-[(4-nitrophenyl)ethynyl]-1H-pyrrole-2-carboxylate (7b, 0.30 g, 1.46 mmol) in

• , 1371, 1332, 1089, 1055, 766, 729, 696, 685; HRMS: [M + H]+ calcd for C13H8INO2, 337.96791; found, 337.97070. 4-Iodo-3-(4-nitrophenyl)-1H-pyrrolo[2,1-c][1,4]oxazin-1-one (19b). To a solution of methyl 1-[(4-nitrophenyl)ethynyl]-1H-pyrrole-2-carboxylate (7b, 0.108 g, 0.400 mmol) in DCM (20 mL), I2 (0.101