Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• substituent in our previous study, for which these copper-catalysed conditions resulted in dimerization [11]. Following the discovery of this substrate-dependent dichotomy with respect to optimal reaction conditions, the entire library of compounds was successfully cyclised. Whilst the yields ranged from low

Microfluidic light-driven synthesis of tetracyclic molecular architectures

• Javier Mateos,
• Nicholas Meneghini,
• Marcella Bonchio,
• Nadia Marino,
• Tommaso Carofiglio,
• Xavier Companyó and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2018, 14, 2418–2424, doi:10.3762/bjoc.14.219

• , producing only traces of the expected sulfur-containing adduct 4i. As a matter of fact, compound 2e showed a high tendency to undergo a light-promoted [2 + 2] dimerization reaction, thus preventing the envisaged [4 + 2] cycloaddition pathway [13]. Next, the chromone scaffold 3a, which is a precursor of

Nucleoside macrocycles formed by intramolecular click reaction: efficient cyclization of pyrimidine nucleosides decorated with 5'-azido residues and 5-octadiynyl side chains

• Jiang Liu,
• Peter Leonard,
• Sebastian L. Müller,
• Constantin Daniliuc and
• Frank Seela

Beilstein J. Org. Chem. 2018, 14, 2404–2410, doi:10.3762/bjoc.14.217

• %) together with the dimeric side product 3 (4.5%, Scheme 1) [37]. The moderate yield of the 5’azido-dC derivative results from incomplete conversion. Possibly, traces of copper used for the Sonogashira cross coupling and high substrate concentration were initiating dimerization of azide 2. Nevertheless, an

• . Conclusion The synthesis of a macrocycle is often described as an intramolecular cyclization of a bifunctional precursor molecule. However, in many cases competition exists with dimerization and polymerization. Therefore, we were delighted to see that the intramolecular cyclization, utilizing dU and dC

Dynamic light scattering studies of the effects of salts on the diffusivity of cationic and anionic cavitands

• Anthony Wishard and
• Bruce C. Gibb

Beilstein J. Org. Chem. 2018, 14, 2212–2219, doi:10.3762/bjoc.14.195

• fluoride and chloride did not induce aggregation of positively charged host 2, this cavitand exhibited marked aggregation as a function of bromide and iodide concentration. Specifically, bromide induced small but significant amounts of dimerization, whilst iodide induced extreme aggregation. Moreover, in

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• -type arrangement in the dimer [34]. Furthermore, the equilibrium between a paramagnetic monomer and a diamagnetic dimer makes the use of electron paramagnetic resonance (EPR) spectroscopy ideal to follow the dimerization process [36]. Mixed-valence and radical-cation interactions in the solid state are

• sometimes described as “conductive” and “isolating” form, respectively. However, in solution both dimers display very low stabilities with dimerization energies of only a few kJ mol−1 at room temperature [36]. Therefore, these weakly associated dimers are virtually absent at ambient conditions in solution

• supramolecular complexes with confined spaces which provide a very high local concentration and shift the equilibrium towards the dimer side. The use of TTF dimerization has been recognized lately as additional possibility to drive motion in MIMs. Recent examples will be discussed in the following section. 2

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• reaction specifically investigated the dimerization of thiols. Some of the experiments carried out by the group were in a flow chemistry set up, exemplifying the scalability of the procedure. In addition, the oxidant that achieves the transformation is molecular oxygen, making this a very sustainable route

A self-assembled photoresponsive gel consisting of chiral nanofibers

• Lei Zou,
• Dan Han,
• Zhiyi Yuan,
• Dongdong Chang and
• Xiang Ma

Beilstein J. Org. Chem. 2018, 14, 1994–2001, doi:10.3762/bjoc.14.174

• compound 3. These two azobenzene moieties within the molecule are close and the dimerization of the UPy moiety results in a more crowded structure. The circular dichroism (CD) spectrum was then measured to trace the different states of aggregation in solution of compound 3 in different solvents. Benzene

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

• Leu13 in receptor binding. Alternatively, since the ComD receptors are predicted to dimerize upon activation, Leu13 may have a role in stabilizing the dimerization process prior to phosphorylating the response regulator, ComE. Lastly, it is possible that CSP1 interacts with the ComD1 receptor using more

Synthesis of pyrimido[1,6-a]quinoxalines via intermolecular trapping of thermally generated acyl(quinoxalin-2-yl)ketenes by Schiff bases

• Svetlana O. Kasatkina,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev,
• Ivan G. Mokrushin and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2018, 14, 1734–1742, doi:10.3762/bjoc.14.147

• be explained by a concurrent process of ketene dimerization (Scheme 2) [29] in comparison to the intermolecular trapping of it by benzalaniline (2a). Since the yields of the target product 3a decreased and the yields of compound 5a increased at prolonged time of reaction, the formation of the target

Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells

• Livia Polgár,
• Eszter Lajkó,
• Pál Soós,
• Orsolya Láng,
• Marilena Manea,
• Béla Merkely,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 1583–1594, doi:10.3762/bjoc.14.136

• cleavable oligopeptide spacers (e.g., GFLG, YRRL) [15][21], dimerization of the targeting GnRH-III unit [22], attachment of drugs through different linkages (e.g., ester, amide or oxime bond) [14][23], and multiplication of drugs [24][25] were pursued in order to achieve an increased antitumor effect. The

• types through the whole concentration range measured. These trends correlate with the antitumor activity of the conjugates. It was also found that the dimerization of Dau containing conjugates (9–11) did not lead to a significant change in toxicity on any cardiac cell types, except conjugate {[4N-MeSer

• ]-GnRH-III(Dau=Aoa-C)}2 (10) that showed higher cytotoxicity on cardiomyocytes. It is worth mentioning that the dimerization increased the enzymatic stability of the conjugates without losing their antitumor effect. Because conjugate 9 with significant antitumor effect did not show cytotoxicity either on

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• reaction pathway to proceed via the corresponding N-phenylnitrilimine. The yields (Table 3) are generally lower than those of reactions performed under thermal conditions – most probably due to the lower stability of the key intermediate – N-phenylnitrilimine – which can undergo dimerization or reverse

An unusual thionyl chloride-promoted C−C bond formation to obtain 4,4'-bipyrazolones

• Gernot A. Eller,
• Gytė Vilkauskaitė,
• Algirdas Šačkus,
• Vytas Martynaitis,
• Ashenafi Damtew Mamuye,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2018, 14, 1287–1292, doi:10.3762/bjoc.14.110

• prepared. Moreover, the structure of a representative 5,5'-dioxo-4,4'-bipyrazole-4,4'-dicarboxylate was confirmed by X-ray crystal structure analysis. Keywords: dimerization; NMR (1H; 13C; 15N); pyrazolones; thionyl chloride; X-ray structure analysis; Introduction Many biologically active substances

• corresponding dimers of type 3 were obtained in moderate to good yields (Scheme 3). In order to check if these dimerization reactions also occur with other 5-hydroxypyrazoles carrying a C=O function at pyrazole C4 we subjected ketone 4 and hydrazide 5 to the same reaction conditions. In both cases, a plethora

• → 3 is unclear. Dimerization by air oxidation can be ruled out as performing the reaction under N2 atmosphere provided the same result. It should be mentioned that for the oxovanadium(V)-mediated dimerization of 4-aroyl-5-hydroxypyrazoles mentioned above a radical mechanism was postulated [32

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• spirocyclization of naphthol carboxylic acid [34]. Later Birman et al. reported a new variation of a chiral I(V) reagent, namely 2-(o-iodoxyphenyl)oxazoline derivative 28 [35]. The reagent was applied to an asymmetric [4 + 2] Diels–Alder dimerization of phenolic derivatives 29 to construct tricyclic derivatives 30

• . Asymmetric oxidation of sulfides by chiral hypervalent iodine reagents. Oxidative dearomatization of naphthol derivatives by Kita et al. [4 + 2] Diels–Alder dimerization reported by Birman et al. m-CPBA guided catalytic oxidative naphthol dearomatization. Oxidative dearomatization of phenolic derivatives by

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

• substantial contribution of 13B to 13A in the ground state. Moreover, it was found that the photochemical behavior of 230 depended on the state of the irradiation medium. For example, the smooth [π10 + π10] dimerization of 13 to give dimeric product 233 was realized with the irradiation (>420 nm) of 13 in a

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

• ). This has been attributed to strong self-association (dimerization) in an antiparallel, head-to-tail orientation in aqueous solution during complex formation with duplex DNA oligomers verified via NOE experiments [61]. They further reported several structurally diverse MGBs, derived from distamycin, in

Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones

• Keshaba N. Parida,
• Gulab K. Pathe,
• Shimon Maksymenko and
• Alex M. Szpilman

Beilstein J. Org. Chem. 2018, 14, 992–997, doi:10.3762/bjoc.14.84

• path to 1,4-dicarbonyl compounds. However, while oxidative dimerization of enolates is fairly straightforward [6][7], the coupling of two dissimilar enolates is contrastingly highly challenging. The more similar in steric and electronic properties the two dissimilar enolates become, the more difficult

• ) with 4 (R1 = Ph, R2 =H) afforded 20 in 51% yield. Since both meso-23 and rac-23 are well-described in the literature [33], we chose to study the diastereoselectivity of the reaction using the dimerization of enol ether 21. The geometry of the TMS enol ether 21 was established as being exclusively Z

Local energy decomposition analysis of hydrogen-bonded dimers within a domain-based pair natural orbital coupled cluster study

• Ahmet Altun,
• Frank Neese and
• Giovanni Bistoni

Beilstein J. Org. Chem. 2018, 14, 919–929, doi:10.3762/bjoc.14.79

• publications [23][24][25][26][27][28][29][30][31][32][33]. We thus only recall here the main features of this technique. Within a supramolecular approach, the energy of a molecular adduct XY relative to the total energies of noninteracting fragments X and Y, i.e, dimerization energy (ΔE), can be written as

• CCSD(T) result of 2.737 Å with a quintuple−ζ basis [71]. The equilibrium ΔEe and zero-point corrected ΔE0 dimerization energies of water and HF dimers are given in Table 1. These correspond to the equilibrium De and zero-point D0 dissociation energies with opposite sign, respectively. The ΔEe value of

• kcal/mol) values at the CCSD(T)/CBS level [74]. It was shown [74] that the effects of quadruple excitations Q (−0.008 ± 0.004 kcal/mol), relativity (0.016 ± 0.001 kcal/mol), and the diagonal Born–Oppenheimer correction (−0.012 ± 0.000 kcal/mol) to the dimerization energy of the HF dimer are negligible

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

Investigating radical cation chain processes in the electrocatalytic Diels–Alder reaction

• Yasushi Imada,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 642–647, doi:10.3762/bjoc.14.51

• the catalytic cycle (Figure 1). The concentration of substrates must be balanced to lengthen the chain process, since a higher concentration of trans-anethole (1) is effective for the bulk SET, but it can also cause undesired self-dimerization. We intentionally stopped the reaction at 0.01 F/mol in

• ). However, some dimerization of trans-anethole (1) via the trapping of the radical cation (1·+) by neutral trans-anethole was also detected in both cases (Scheme 2). Since the undesired dimerization can decrease the current efficiency, we raised the amount of isoprene (2) from 3 to 10 equivalents in order

• efficiency of 3167% (Table 2, entry 4). Under these conditions, the undesired dimerization of trans-anethole (1) took place to give the dimer 4. However, we found that the electrochemical radical cation Diels–Alder reaction was also possible from the dimer, whose photochemical version was reported by Yoon

An air-stable bisboron complex: a practical bidentate Lewis acid catalyst

• Longcheng Hong,
• Sebastian Ahles,
• Andreas H. Heindl,
• Gastelle Tiétcha,
• Andrey Petrov,
• Zhenpin Lu,
• Christian Logemann and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2018, 14, 618–625, doi:10.3762/bjoc.14.48

• procedure for the synthesis of bisboron compound A via a dimerization requires a high reaction temperature (Scheme 3, top). Due to the use of volatile BCl3, the dimerization reaction is usually carried out in a sealed pressure tube. Using Schlenk technique, the procedure affords compound A in good yield

• optimized procedure, BBr3 was used to replace BCl3 and the dimerization reaction can be carried out in a normal Schlenk tube without any solvent. The methylation reagent, AlMe3 can be added in situ followed by the complexation with pyridazine. The one-pot procedure is also applicable to the synthesis of

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• dimers formed in a Diels–Alder dimerization process by heating the corresponding Mannich bases under reflux in dichloromethane for 2 hours. In the synthesis of 3,4-dihydro-2-aryl-2H-benzo[f]chromenes and 2-aryl-6,7-dimethylchromans starting from substituted styrenes and 1-dimethylaminomethyl-2-naphthol

• unexpected side products. As mentioned above [71], Osyanin et al. reported the synthesis of Uvaria scheffleri alkaloid (±)-schefflone. In this publication, the dimerization of the o-QM resulting in intermediate 41 is a key step in the synthesis of the final natural trimer compound. Reactions with C=N

• various conditions applied in the synthesis of amidoalkylnaphthols 4. Formation and substrate scope of phenolic Mannich bases. Reactions of o-QMs with different dienophile species. Dimerization of o-QMs. Acknowledgements The authors thank the Ministry of National Economy, National Research Development

Oxidative cycloaddition of hydroxamic acids with dienes or guaiacols mediated by iodine(III) reagents

• Hisato Shimizu,
• Akira Yoshimura,
• Keiichi Noguchi,
• Victor N. Nemykin,
• Viktor V. Zhdankin and
• Akio Saito

Beilstein J. Org. Chem. 2018, 14, 531–536, doi:10.3762/bjoc.14.39

• of 1a with simple dienes or guaiacols, benzoyl anhydride was detected as a byproduct. Since benzoyl anhydride is known to be formed via the dimerization of benzoylnitroso compounds [35], these results suggest that acylnitroso species would be generated from 1a by iodine(III) reagents. Therefore, the

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• catalytic amount of copper salt was required in this reaction. The hydrogens on the ortho and para positions of phenols have higher reactivity. Thus, undesired side reactions were often involved in the trifluoromethylation of less substituted phenols, including oxidative dimerization and oligomerization

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• -inflammatory signaling cascade. The lipid A portion of hexaacyl LPS (e.g., in E. coli LPS) is recognized and bound by a co-receptor protein MD-2 which is physically asssociated with TLR4. The binding of lipid A initiates dimerization of two copies of the TLR4∙MD-2–LPS complexes which results in the formation

• -inflammatory signaling and activation of the host innate immunity (Figure 3B) [42][45][46]. Compounds which compete with LPS in binding to the same site on MD-2 are capable of inhibiting the induction of the signal transduction pathway by preventing the LPS-induced receptor complex dimerization (Figure 3C

•  4B) [42][64]. Thus, lipid A directly participates in the formation of an active multimeric ligand–receptor complex, whereas the tightness and efficiency of dimerization strongly depends on specific structural characteristics such as the acylation pattern and the number of negative charges (e.g

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• and phenyl-substituted tetraoxaadamantanes 1a and 1b were obtained by Arnold [1] and Almqvist [2] through the dimerization of β-ketoaldehydes (reactions 1 and 2 in Scheme 1). This was confirmed by Opitz et al., but the attempted synthesis of further analogs by these procedures failed [3]. Takeda et al

• . performed the dimerization of β-ketoaldehydes with SO2Cl2 (reaction 3 in Scheme 1) [4], and the X-ray crystal structure of 1b was reported [5]. Chekalov et al. described the preparation of the tetramethyl derivative 1d by dimerization of acetylacetone induced by SiF4 (reaction 4 in Scheme 1) [6] and also

• dimerization of dipivaloylketene (2), itself obtained in high yield by FVP of furan-2,3-dione 6 (Scheme 3). Ketene 3 reacts with a variety of nucleophiles in an addition reaction to the ketene function, thereby transforming the ketene to enol derivatives 14 or 9 of 1,3-dioxin-4-ones. Subsequently, these enols