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

• also showed a strong increase in 2-AA and DHQ production, while not affecting the overall production of AQ’s. PqsR In 2017 Kamal et al. investigated the structure–functionality relationship of compounds targeting PqsR. They differentiated between agonists, neutral agonists, inverse agonists and

• several alkylquinolone compounds were investigated in a structure–functionality relationship manner, resulting in four different profiles: (a) agonists, (b) antagonists, (c) inverse agonists and (d) biphasic modulators. These studies revealed that pyocyanin production is only decreased significantly when

• the QS modulators are inverse agonists. It was hypothesized that the already mentioned 3-position is crucial for the functionality. Depending on the groups installed in this position and, hence, the different ligand–protein interactions they introduce, compounds are either agonists, antagonists, or

Synthesis of functionalised β-keto amides by aminoacylation/domino fragmentation of β-enamino amides

• Pavel Yanev and
• Plamen Angelov

Beilstein J. Org. Chem. 2018, 14, 2602–2606, doi:10.3762/bjoc.14.238

• necessitates either a double deprotonation to ambident 1,3-dianions [10] or proper masking of the amide functionality prior to deprotonation [11][12]. Consequently, there are very few published reagents that are synthetically equivalent to primary or secondary amide enolate synthons. With regard to acylation

• reactions, maybe most important among these are some nitriles, which can be successfully acylated at the alpha position [13][14][15] and then hydrated [13][16][17][18][19][20] to reveal a primary amide functionality. The dianion of silylated acetamide is another such example, although with very limited

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

• eight tautomeric forms [28], their N(1')-substituted derivatives, lacking a functionality on pyrazole C-4, can only exist in three equilibrating tautomers (OH, CH and NH) [18][29]. Therefore, further heterocyclizations of 4 were performed with monosubstituted hydrazine derivatives. The reaction with

Practical tetrafluoroethylene fragment installation through a coupling reaction of (1,1,2,2-tetrafluorobut-3-en-1-yl)zinc bromide with various electrophiles

• Ken Tamamoto,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 2375–2383, doi:10.3762/bjoc.14.213

• ., –(CF2)n–, in various fields, such as medicine and materials sciences [1][2][3][4], because incorporation of multiple fluorine atoms into organic substances causes dramatic alterations in the chemical and physical properties of substances, which may significantly enhance their potential functionality [5

• in 60% and 64% yields, respectively. Interestingly, the reaction using ethyl o-iodobenzoate (3j) quite efficiently proceeded to give the coupling product 4j almost quantitatively. Comparing the result from the reaction with the para-substituted analog 3f, the ester functionality at the ortho-position

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

• 10.3762/bjoc.14.206 Abstract The stereoselective total synthesis of strongylodiol H and I has been accomplished. The synthetic procedure comprised the stereoselective reduction of a ketone functionality in an ene–yne–one employing CBS as a catalyst and a Cadiot–Chodkiewicz coupling reaction as the key

Coordination-driven self-assembly of discrete Ru₆–Pt₆ prismatic cages

• Aderonke Ajibola Adeyemo and
• Partha Sarathi Mukherjee

Beilstein J. Org. Chem. 2018, 14, 2242–2249, doi:10.3762/bjoc.14.199

• , the use of a single metal and a single organic ligand design may limit the structural diversity as well as the functionality of homometallic supramolecular architectures. In the last few years, enormous efforts have been channeled towards multicomponent self-assembly involving the construction of

Investigation of the electrophilic reactivity of the biologically active marine sesquiterpenoid onchidal and model compounds

• Melissa M. Cadelis and
• Brent R. Copp

Beilstein J. Org. Chem. 2018, 14, 2229–2235, doi:10.3762/bjoc.14.197

• deconvoluted (+)-ESI mass spectrum, identifying a total lysozyme modification yield of 15% (Table 1). The presence of a large amount of unmodified lysozyme (85%), even after 72 h, was attributed to the slow reactivity of the enol acetate functionality of onchidal, as observed in the original model studies

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

• rearrange by a ring-degenerate process promoted by an increasing electron-donor strength of the imine functionality. It was further demonstrated that this rearrangement could be utilized as a reliable synthetic tool, with 1-phenyl-1H-1,2,3-triazole-4-carbaldehyde being used to prepare 1-substituted-4-formyl

• (Table 2, entries 1–5). Evaluation of the formyltriazole substituent identity on the rearrangement surprisingly showed that even at room temperature those analogs with electron-poor nitro functionality underwent slow but consistent rearrangement (Table 2, entries 6–8). In contrast, all other analogs

• formyltriazole 1a showed enhanced populations of rearranged formyltriazole and iminotriazole products lacking nitro functionality (Table 2, entries 6–8, and 20). This can be attributed to a two-fold influence by the nitro substituent. As an electron-poor formyltriazole, 1a promotes forward progress of the

Cobalt-catalyzed nucleophilic addition of the allylic C(sp³)–H bond of simple alkenes to ketones

• Tsuyoshi Mita,
• Masashi Uchiyama,
• Kenichi Michigami and
• Yoshihiro Sato

Beilstein J. Org. Chem. 2018, 14, 2012–2017, doi:10.3762/bjoc.14.176

• bonds; cobalt; ketones; Introduction The cleavage of C–H bonds of unreactive hydrocarbon followed by functionalization should be an ideal method for constructing complex molecules without introduction of reactive functionality in advance [1][2][3][4][5][6][7][8][9]. Since terminal alkenes including α

• a slightly higher yield (78%). Electron-withdrawing substituents such as F (2d) and CO2Me (2e) also promoted the reaction with similar levels without damaging the ester functionality. Furthermore, 2-naphtophenone (2f) and propiophenone (2g) were tolerated well, affording branched products

An amphiphilic pseudo[1]catenane: neutral guest-induced clouding point change

• Tomoki Ogoshi,
• Tomohiro Akutsu and
• Tada-aki Yamagishi

Beilstein J. Org. Chem. 2018, 14, 1937–1943, doi:10.3762/bjoc.14.167

• component because of their high functionality and superior host–guest properties with neutral guests [12][13][14][15][16]. The amphiphilic pillar[n]arenes 1 and 2 exhibit clouding points at 41 and 42 °C, respectively [5][6]. The oligo(ethylene oxide) moieties are solvated with water molecules at room

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• will maintain the reaction temperature and components viz. valves, measurement devices and so on. As mentioned earlier, a list of various terms used in this article is given in Table 3. The functionality and nature of the setup can change with the chemistry under investigation and the experience of an

Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepine derivatives by [3⁺ + 2]-cycloaddition/rearrangement reactions

• Lin-bo Luan,
• Zi-jie Song,
• Zhi-ming Li and
• Quan-rui Wang

Beilstein J. Org. Chem. 2018, 14, 1826–1833, doi:10.3762/bjoc.14.155

• electron-withdrawing N-acetyl functionality in compounds 8 was introduced to conceal the basicity of the N(1) atom, thus avoiding the plausible disturbance in the following cationic polar cycloaddition/rearrangement reaction. After the accomplishment of the synthesis of key intermediates 8, we tried to

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• ) and spiropyrrolidines 125 were isolated in good to excellent yields (Scheme 46). However, the presence of an electron-donating functionality at para-position to the phenolic group induced no spirocyclization product. In 2016, Bray and Shirley [125] reported the oxidative spirocyclization of meta

• . This spirocyclic functionality is the basic nucleus found in the phorbaketal family of natural products. 5.2. Stereoselective synthesis of chiral spirocyclic ketals Recently, Ishihara and co-workers [126] synthesized chiral C2-symmetric iodoarene 129a and 129b (Figure 3) in few steps and used as

• of palmarumycin CP1 were synthesized later which were showing good thioredoxin–thioredoxin reductase (Trx-1/TrxR) inhibitory activity [129]. It was observed that the introduction of enone functionality in naphthoquinone spiroketal enhances the biological activity of palmarumycin 138. Furthermore, Ley

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• disubstituted C2-acyloxylglycoside. A plausible mechanism of the reaction is shown in Figure 8. The first step of the reaction between glycal 161 and (diacyloxyiodo)benzene formed the glycosyl ester intermediate 162 bearing a phenyl iodonium(III) functionality at C2, which was transformed to a diacyloxylated

•  22. Either (diacetoxyiodo)benzene or (dibenzoyloxyiodo)benzene could serve as an efficient oxidant, and the reactions utilizing them gave the products installing either the acetate or benzoate functionality, respectively, at the C2-position. Both glucal 115 and galactal 167 were amenable to the

Mild and selective reduction of aldehydes utilising sodium dithionite under flow conditions

• Nicole C. Neyt and
• Darren L. Riley

Beilstein J. Org. Chem. 2018, 14, 1529–1536, doi:10.3762/bjoc.14.129

• % (Table 3, entries 3.1 and 3.2). The reaction was further tested by the reduction of 3-acetylbenzaldehyde which contained an aldehyde and ketone functionality on the same molecular scaffold. In this instance an aldehyde conversion of 85% was observed with <1% reduction of the ketone (Table 3, entry 3.8

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• addition. The latter would release the iodoarene that could be coupled to a suitable functionality previously introduced on the starting material. The strategy has been first validated from TMS-protected alkyne derivatives via a tandem of C(sp3)–H amination/sila-Sonogashira–Hagihara coupling (Scheme 43

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• -diaminocyclohexane moiety from (1R,2R) to (1S,2S) without loss of activity or selectivity. Bifunctional organic molecules combining the thiourea moiety with a tertiary amine functionality are remarkably useful catalysts capable of simultaneous activation of both electrophiles and nucleophiles [51]. Therefore, a

• reactions, optically active calix[4]arene-imine derivative 92 containing an L-prolinamide functionality was also tested as a catalyst for enantioselective aldol reactions between 70 and a variety of aromatic aldehydes 72. The anti-aldol adducts were obtained in high yields and ees (Scheme 26). Based on the

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• (the carboxylate or alcoholate) is covalently attached to the aryl iodide and hence does not get lost during the reaction cascade (Scheme 1, reaction (d)). This is very effective, if this ortho-functionality is a desired part of the final reaction product or if it can be readily transformed into

Rapid transformation of sulfinate salts into sulfonates promoted by a hypervalent iodine(III) reagent

• Elsa Deruer,
• Vincent Hamel,
• Samuel Blais and
• Sylvain Canesi

Beilstein J. Org. Chem. 2018, 14, 1203–1207, doi:10.3762/bjoc.14.101

• , decarboxylation, and fragmentation [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. The sulfonate group is a useful functionality frequently employed as a leaving group in substitution reactions. Production of sulfonates [28] from alcohols generally involves reaction with a

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• bonds and functionality towards the construction of synthetic scaffolds. The synthesis of spirocyclic oxindoles has always been of key interest to organic chemists because of significant biological activity [16][17][18][19][20] and their presence in naturally occurring molecules [21][22][23

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• -catalyzed, stereo- and regioselective epoxide opening and subsequent nucleophilic substitution of an azide functionality. This approach enables the synthesis of the naturally D- and unnaturally L-configured GalNAc, as well as both enantiomers of the largely unknown N-acetylidosamine (IdoNAc). Keywords

• of the four desired stereogenic centers. By extending compound 5 via a Horner–Wadsworth–Emmons (HWE) reaction [15] and subsequent stereoselective introduction of the corresponding nitrogen functionality, a route to four different 2-amino sugar stereoisomers has been elaborated. Results and Discussion

• -diethyl tartrate (L-DET) directing the reaction towards the D-galacto-configured epoxythreitol 5a. Alternatively, epoxidation of 4b with D-DET was used to access L-galacto-configured epoxythreitol 5b. A procedure by Miyashita et al. [19] for nucleophilic substitution of epoxides by an azide functionality

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

• ]. Guanidine is the side-chain functionality of arginine, an active component of the catalytic center of some nucleases, e.g., Staphylococcal nuclease [70] and topoisomerase [71]. Additionally, it is a substructure of guanine base that in hammerhead [72][73] and hairpin [74] ribozymes participates in proton

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• , reduction, nitro-aldol reaction, and dehydration (Scheme 1). Methylation of the ester 2 in the alpha position proceeded easily with LDA as a base and methyl iodide as an alkylating agent. The ester functionality was then reduced with DIBAL in dichloromethane to afford aldehyde 4 in 90% yield. A base

Electrochemical Corey–Winter reaction. Reduction of thiocarbonates in aqueous methanol media and application to the synthesis of a naturally occurring α-pyrone

• Ernesto Emmanuel López-López,
• José Alvano Pérez-Bautista,
• Fernando Sartillo-Piscil and
• Bernardo A. Frontana-Uribe

Beilstein J. Org. Chem. 2018, 14, 547–552, doi:10.3762/bjoc.14.41

• functionality [34], which was not reduced under the reaction conditions. The high stereospecificity of this electrochemical Corey–Winter-type reaction might be explained in terms of the stabilizing β-oxygen effect [35][36] of the radical intermediate E. This stereoelectronic interaction, which refers to the