Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• benzyl improves the in vitro antistaphylococcal activity. In contrast, the incorporation of smaller heterocycles like pyridine and imidazole as well as isosteric benzimidazole instead of the indole moieties lead to a loss of antibacterial activity. Kennedy et al. could synthesize a 2-phenyl derivative

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• solution in monomeric form. This product was used for reactions with α-hydroxyiminoketones leading to a new class of 2-unsubstituted imidazole 3-oxides bearing the adamantyloxy substituent at N(1). Their reactions with 2,2,4,4-tetramethylcyclobutane-1,3-dithione or with acetic acid anhydride occurred

• analogously to those of 1-alkylimidazole 3-oxides to give imidazol-2-thiones and imidazol-2-ones, respectively. Treatment of 1-(adamantyloxy)imidazole 3-oxides with Raney-Ni afforded the corresponding imidazole derivatives without cleavage of the N(1)–O bond. Finally, the O-alkylation reactions of the new

• imidazole N-oxides with 1-bromopentane or 1-bromododecane open access to diversely substituted, non-symmetric 1,3-dialkoxyimidazolium salts. Adamantyloxyamine reacts with glyoxal and formaldehyde in the presence of hydrobromic acid yielding symmetric 1,3-di(adamantyloxy)-1H-imidazolium bromide in good yield

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• nucleophilic attack at the chloromethyl moiety by the imidazole of His57, to afford the artificial metathase ArM 3 (Scheme 14). Matsuo et al. tested the RCM of three different substrates with the protein-free catalyst 66 as well as ArM 3 (Table 7). No RCM occurred with substrate 52 (<2 TON) with catalyst 66

Synthesis of C₃-symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step

• Sambasivarao Kotha and
• Saidulu Todeti

Beilstein J. Org. Chem. 2019, 15, 371–377, doi:10.3762/bjoc.15.33

• tetrahydrofuran (THF) to obtain the N-Boc-serine methyl ester (5) in 93% yield [42]. Afterwards, the protected methyl ester 5 was subjected to iodination in the presence of iodine (I2), triphenylphosphane (PPh3) and imidazole in CH2Cl2 at 0 °C to deliver the iodo derivative 6 in 63% yield [43][44]. Finally, the

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

• , reaction with pyrrolidine, imidazole, methanol, allyl alcohol, benzyl alcohol and 9-fluorenemethanol (FmOH) provided the corresponding urea 30, N-carbamoyl imidazole 31 and carbamates 32–35, respectively, in good yields (69–80%). The reaction of isocyanate 28 with tert-butanol was sluggish even by heating

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• ; f) Cs2CO3, MeOH; g) t-BuMe2SiCl, imidazole, DMF; h) NaIO4, KMnO4, then CH2N2, ether; i) TBAF; j) 6 M HCl. Synthesis of dimethyl ester of (2S,3R)-2 employing (1S)-2-exo-methoxyethoxyapocamphane-1-carboxylic acid as a chiral auxiliary. Reagents and conditions: a) PhSeCl, MeOH; b) H2C=CHCH2SnBu3, ether

• and conditions: a) BuLi, THF, then H2C=CHCHO; b) MeI, K2CO3, acetone; c) I2, THF; d) EtCOO– Cs+, DMF; e) K2CO3, EtOH; f) t-BuMe2SiCl, imidazole, DMAP, DMF; g) Na, liquid NH3; h) Boc2O, NaH, THF; i) KOH, MeOH/H2O; j) CH2N2, ether; k) TBAF, THF; l) O2, Pt. Synthesis of N-Boc-protected dimethyl ester of

• (2S,3R)-2 via Sharpless epoxidation. Reagents and conditions: a) TBHP, D-(−)-DIPT, Ti(OiPr)4, MS, CH2Cl2; b) t-BuMe2SiCl, imidazole, DMAP, DMF; c) NaIO4, RuO2, AcOEt/H2O. Synthesis of (2S,3S)-2 from the imide 51. Reagents and conditions: a) NaBH4, MeOH/CH2Cl2; b) Ac2O, pyridinium perchlorate; c) furan

Gold-catalyzed ethylene cyclopropanation

• Silvia G. Rull,
• Andrea Olmos and
• Pedro J. Pérez

Beilstein J. Org. Chem. 2019, 15, 67–71, doi:10.3762/bjoc.15.7

• directly converted into ethyl 1-cyclopropylcarboxylate upon reaction with ethyl diazoacetate (N2CHCO2Et, EDA) in the presence of catalytic amounts of IPrAuCl/NaBArF4 (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene; BArF4 = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate). Keywords: carbene

• given our experience with group 11 metal-based catalysts for carbene-transfer reactions from diazoacetates [15][16], we have investigated this transformation and found that the gold complex IPrAuCl (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene) along with one equivalent of NaBArF4 (BArF4

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

• , acrylamide, N,N'-bisacrylamide, ATP, bromophenol blue, agarose, EDTA, IPTG, ampicillin, sodium dodecylsulfate, imidazole and DMF were purchased from Panreac (Spain, Barselona). Ethanol was purchased from MedChemProm. Coomassie Brilliant Blue R-250 was purchased from Bio-Rad (USA, CA). Bacto yeast extract

• -equilibrated with 50 mM Tris-HCl and 200 mM NaCl at pH 8.0. Ballast proteins were eluted with a solution, containing 50 mM Tris-HCl, 50 mM imidazole, and 200 mM NaCl, pH 8.0 (4 CV, flow rate 2 mL/min). The target enzyme was eluted with solution, contained 50 mM Tris-HCl, 250 mM imidazole, and 200 mM NaCl, pH

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• promising anticancer activity [34], thereby showing the importance of this merged heterocyclic skeleton (Figure 1). The formation of the chromene and imidazole rings in a single-step procedure was independently discovered by us [35][36] and Proença et al. [37][38], who identified 2-iminochromene 3 to be the

Green synthesis of new chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5-diones from the corresponding α-amino acid arylhydrazides in aqueous medium

• Nadia Bouzayani,
• Jamil Kraїem,
• Sylvain Marque,
• Yakdhane Kacem,
• Abel Carlin-Sinclair,
• Jérôme Marrot and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2018, 14, 2923–2930, doi:10.3762/bjoc.14.271

• refluxing α-amino acid phenylhydrazides with levulinic acid in toluene led to the corresponding dihydro-1H-pyrrolo[1,2-a]imidazole-2,5-diones. These authors explained clearly the behavior of the solvent and its influence in the reaction. In addition, substituted 1-hydroxy-1H-imidazo[2,1-a]isoindole-2,5(3H

The influence of the cationic carbenes on the initiation kinetics of ruthenium-based metathesis catalysts; a DFT study

• Magdalena Jawiczuk,
• Angelika Janaszkiewicz and
• Bartosz Trzaskowski

Beilstein J. Org. Chem. 2018, 14, 2872–2880, doi:10.3762/bjoc.14.266

• stable in water and, therefore, environmentally-friendly. The idea of incorporating a quaternary ammonium moiety into the imidazole part of the carbene was later expanded by several other groups, including a number of new water-soluble catalysts synthesized by Skowerski et al. [23][24]. In the meantime

• affect the efficiency of the catalyst in model metathesis reactions in comparison to Skowerski’s complexes with only one –CH2– unit. Curiously, carbenes with the cationic group even closer to the imidazole moiety (with no spacer) or incorporated into the imidazole core have been synthesized only very

• recently and examples of their transition metal complexes are scarce. In 2013 Ganter described a cationic NHC with a fused pyridinium moiety and the formal +1 charge just one bond away from the imidazole core [27]. In 2017 César synthesized a cationic imidazolylidene NHC with an ammonium tag attached

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

• ) 5 mol % Grubbs–Hoveyda II, 1,2-DCE, 50 °C. Synthesis of alternative eastern fragment 23. Reagents and conditions: a) TBSCl, imidazole, CH2Cl2, rt; b) H2NNH2·H2O, MeOH, reflux; c) p-Ns-Cl, Et3N, CH2Cl2, 0 °C. Synthesis of 4. Reagents and conditions: a) PPh3, DEAD, THF, 0 °C to rt; b) Grubbs–Hoveyda

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• from the common 2-azidoglucose precursor 7, the 4,6-O-benzylidene group was removed with TsOH to give the 4,6-diol in 95% yield, followed by selective 6-O-protection using TBDPS-Cl and imidazole (IM) in 90% yield. The 4,6-O-benzylidene motif could also be regioselectively opened using triethylsilane

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• , triazolo[1,2-a]indazoletrione derivatives, tetrasubstituted imidazole derivatives, aromatic/aliphatic sulfide derivatives, and N-substituted pyrrole derivatives. These catalysts were used in cellulose hydrolysis, cellobiose hydrolysis, production of fatty acid ethyl ester, the transesterification of

• 2,2'-bipyridine 25 using the reaction of chlorosulfonic acid and 2,2'-bipyridine as well as its application for the synthesis of the various xanthene derivatives 24, 27, and 28 [41]. In another study, the sulfonated imidazole 26 was prepared via the dropwise addition of chlorosulfonic acid to a

• stirred solution of imidazole in dry CH2Cl2 in an ice bath. In the next step, sulfuric acid 98% was added dropwise to the reaction mixture containing the sulfonated imidazole at room temperature to obtain 1,3-disulfo-1H-imidazolium hydrogen sulfate [Dsim]HSO4 (26) as a viscous pale yellow oil catalyst

Ring-opening metathesis of some strained bicyclic systems; stereocontrolled access to diolefinated saturated heterocycles with multiple stereogenic centers

• Zsanett Benke,
• Melinda Nonn,
• Márton Kardos,
• Santos Fustero and
• Loránd Kiss

Beilstein J. Org. Chem. 2018, 14, 2698–2707, doi:10.3762/bjoc.14.247

• interactions in the intermediate phase between the catalyst chlorine and the substrate may be responsible for the accomplishments of the reactions, which were deeply investigated and discussed in the literature [33][34][35][36][37] and see references therein. In our case it was observed that the imidazole

Transition metal-free oxidative and deoxygenative C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyl lithium as an efficient synthetic approach to azaheterocyclic carboranes

• Lidia A. Smyshliaeva,
• Mikhail V. Varaksin,
• Pavel A. Slepukhin,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2018, 14, 2618–2626, doi:10.3762/bjoc.14.240

• 10.3762/bjoc.14.240 Abstract The direct C–H functionalization methodology has first been applied to perform transition metal-free C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyllithium. This atom- and step-economical approach, based on one-pot reactions of nucleophilic substitution of

• hydrogen (SNH) in non-aromatic azaheterocycles, affords novel imidazolyl-modified carboranes of two types (N-oxides and their deoxygenative analogues), which are particularly of interest in the design of advanced materials. Keywords: carboranes; C–H functionalization; C–H/C–Li cross-coupling; 2H-imidazole

• reactions to functionalize non-aromatic heterocycles. In particular, only few examples of SNH reactions are available in the chemistry of 2H-imidazole 1-oxides [57][58][59][60] that are of interest as promising pharmacoactive azaheterocyclic compounds [61][62][63][64][65]. In this paper, we wish to report

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• magnesium enolate of malonic acid half ester, prepared in situ from potassium methyl malonate, MgCl2 and triethylamine in acetonitrile, was added [24][25]. The acylation of magnesium methyl malonate by the preformed imidazole 3 led to the desired bifunctional starting material 4 in good yield (79

Stereoselective total synthesis and structural revision of the diacetylenic diol natural products strongylodiols H and I

• Pamarthi Gangadhar,
• Sayini Ramakrishna,
• Ponneri Venkateswarlu and
• Pabbaraja Srihari

Beilstein J. Org. Chem. 2018, 14, 2313–2320, doi:10.3762/bjoc.14.206

• ) Red-Al, anh. Et2O, −20 °C, 8 h, 95%; (c) (i) DMSO, CH2Cl2, (COCl)2, −78 °C, (ii) TMS-C≡CH, n-BuLi, THF, −78 °C to rt, 3 h, 89%; (d) K2CO3, MeOH, 0 °C to rt, 1 h, 92%; (e) TBSCl, imidazole, 0 °C to rt, 1 h, 98%; (f) I2, TPP, imidazole, 0 °C to rt, 1 h, 92%. Stereoselective synthesis of (R)-25. Reagents

• and conditions: (a) CuCl, NH2OH·HCl, 30% n-BuNH2, Et2O, 1 h, 68%; (b) DMP, CH2Cl2, 0 °C to rt, 1 h, 87%; (c) (S)-CBS catalyst, BH3·DMS, THF, −50 °C, 16 h, 85%. Synthesis of strongylodiol H (9). Reagents and conditions: (a) TBDPSCl, imidazole, CH2Cl2, 0 °C to rt, 2 h, 95%; (b) PPTS, MeOH, 0 °C to rt, 2

• ) TBDPSCl, imidazole, CH2Cl2, 0 °C to rt, 1 h, 96%; (ii) PPTS, MeOH, 0 °C to rt, 2 h, 87%; (iii) IBX, DMSO/THF 1:1, 0 °C to rt, 1 h, 98%; (b) 16, n-BuLi, THF, −78 °C to rt, 2 h, 81%; (c) TBAF, THF, 0 °C to rt, 2 h, 82%. Comparison of 1H and 13C NMR data of strongylodiol H (isolated natural product vs

Selective formation of a zwitterion adduct and bicarbonate salt in the efficient CO₂ fixation by N-benzyl cyclic guanidine under dry and wet conditions

• Yoshiaki Yoshida,
• Naoto Aoyagi and
• Takeshi Endo

Beilstein J. Org. Chem. 2018, 14, 2204–2211, doi:10.3762/bjoc.14.194

• was estimated by using DFT calculation with B3LYP/6-31G* method (Wavefunction, Inc., Spartan’06 Windows version 1.1.0) [41]. Synthesis of N-benzyl cyclic guanidine 2-Benzylamino-4,5-dihydro-1H-imidazole (N-benzyl cyclic guanidine, 1) was synthesized according to the literature [42]. mp 79.9–83.1 °C

Bi-mediated allylation of aldehydes in [bmim][Br]: a mechanistic investigation

• Mrunesh Koli,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2018, 14, 2198–2203, doi:10.3762/bjoc.14.193

•  1, entry 16). In addition, as previously reported in case of crotylation [40], the allylation did not proceed in absence of oxygen (Table 1, entry 17), or when the C-2 imidazole proton was absent in the RTIL (in 1-butyl-2,3-dimethylimidazolium bromide ([bmmim][Br]), Table 1, entry 18). This result

Chiral bisoxazoline ligands designed to stabilize bimetallic complexes

• Deepankar Das,
• Rudrajit Mal,
• Nisha Mittal,
• Zhengbo Zhu,
• Thomas J. Emge and
• Daniel Seidel

Beilstein J. Org. Chem. 2018, 14, 2002–2011, doi:10.3762/bjoc.14.175

• instance, treatment of 6 with two equivalents of copper perchlorate hexahydrate led to the formation of a bis-copper complex [49][50]. The two Cu(ΙΙ) ions, which have a Cu∙∙∙Cu distance of 2.947 Å, are coordinated to the pentadentate bisoxazoline-imidazole moiety and are bridged by the central phenoxy

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• -introduced into the catalytic cycle. Several copper salts (CuCl, CuCl2, CuOAc and Cu(OAc)2) were evaluated as part of optimizing the reaction conditions and they all provided poor yields. 3.3.3 Acetoxysulfenylation of Baylis–Hillman alcohols. Yadav and Aswathi reported a regioselective CuI-imidazole

Phosphoramidite building blocks with protected nitroxides for the synthesis of spin-labeled DNA and RNA

• Timo Weinrich,
• Eva A. Jaumann,
• Ute M. Scheffer,
• Thomas F. Prisner and
• Michael W. Göbel

Beilstein J. Org. Chem. 2018, 14, 1563–1569, doi:10.3762/bjoc.14.133

• , Et3N, CH2Cl2, rt, 4.5 h. Synthesis of phosphoramidite 8. Reagents and conditions: (a) Addition of 10, diisopropylethylamine, 1-propanol, 75 °C, 7 h, rt, 14 h; (b) 7 N NH3 in MeOH, 0 °C → rt, 3 h; (c) dimethoxytrityl chloride, pyridine, rt, 20 h; (d) tert-butyldimethylsilyl chloride, imidazole, DMF, rt

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

• significant antibacterial activity against Gram-positive bacterial strains [50]. Several other distamycin analogs were synthesized by replacing one or more pyrrole rings with other heterocycles such as pyrazoles [51], benzofurans [52], thiazoles, thiophenes, imidazole and oxazoles [53] in order to establish a

• possess the ideal crescent shape required to wrap around the minor groove of DNA, which limit their efficacy to recognize longer stretches of DNA sequence. In order to achieve better sequence specificity, a series of oligomeric “hairpin (HP)” polyamides containing pyrrole and imidazole ring systems (Py/Im

• ) were designed and synthesized by Dervan et al. and followed by other groups. It was observed that pyrrole/imidazole polyamides were able to bind side-by-side in the minor groove of DNA with high affinity and in a sequence-specific manner. Crystal structure studies confirmed the existence of a hydrogen

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