N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

The synthesis of nitrogen-containing heterocycles, including natural alkaloids and other compounds presenting different types of biological activities have proved to be successful employing chiral sulfinyl imines derived from tert-butanesulfinamide. These imines are versatile chiral auxiliaries and have been extensively used as eletrophiles in a wide range of reactions. The electron-withdrawing sulfinyl group facilitates the nucleophilic addition of organometallic compounds to the iminic carbon with high diastereoisomeric excess and the free amines obtained after an easy removal of the tert-butanesulfinyl group can be transformed into enantioenriched nitrogen-containing heterocycles. The goal of this review is to the highlight enantioselective syntheses of heterocycles involving the use of chiral N-tert-butanesulfinyl imines as reaction intermediates, including the synthesis of several natural products. The synthesis of nitrogen-containing heterocycles in which the nitrogen atom is not provided by the chiral imine will not be considered in this review. The sections are organized according to the size of the heterocycles. The present work will comprehensively cover the most pertinent contributions to this research area from 2012 to 2020. We regret in advance that some contributions are excluded in order to maintain a concise format.We thank the continuous financial support from the Spanish Ministerio de Economía y Competitividad (MINECO; project CTQ2014-53695-P, CTQ2014-51912-REDC, CTQ2016-81797-REDC, CTQ2017-85093-P), Ministerio de Ciencia, Innovación y Universidades (RED2018-102387-T, PID2019-107268GB-100), FEDER, the Generalitat Valenciana (PROMETEOII/2014/017), and the University of Alicante (VIGROB-068). We are also grateful for the financial support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The Energy Density of "Wound" Fields in a Toroidal Universe

The observational limits on the present energy density of the Universe allow for a component that redshifts like $1/a^2$ and can contribute significantly to the total. We show that a possible origin for such a contribution is that the universe has a toroidal topology with "wound" scalar fields around its cycles.Comment: 11 pages, 1figur

Effect Of Etching Time And Light Source On The Bond Strength Of Metallic Brackets To Ceramic

This study evaluated the bond strength of brackets to ceramic testing different etching times and light sources for photo-activation of the bonding agent. Cylinders of feldspathic ceramic were etched with 10% hydrofluoric acid for 20 or 60 s. After application of silane on the ceramic surface, metallic brackets were bonded to the cylinders using Transbond XT (3M Unitek). The specimens for each etching time were assigned to 4 groups (n=15), according to the light source: XL2500 halogen light, UltraLume 5 LED, AccuCure 3000 argon laser, and Apollo 95E plasma arc. Light-activation was carried out with total exposure times of 40, 40, 20 and 12 s, respectively. Shear strength testing was carried out after 24 h. The adhesive remnant index (ARI) was evaluated under magnification. Data were subjected to two-way ANOVA and Tukey's test (α=0.05). Specimens etched for 20 s presented significantly lower bond strength (p0.05) were detected among the light sources. The ARI showed a predominance of scores 0 in all groups, with an increase in scores 1, 2 and 3 for the 60 s time. In conclusion, only the etching time had significant influence on the bond strength of brackets to ceramic.223245248Barghi, N., Fischer, D.E., Vatani, L., Effects of porcelain leucite content, types of etchants, and etching time on porcelaincomposite bond (2006) J Esthet Restor Dent, 18, pp. 47-52Nagayassu, M.P., Shintome, L.K., Uemura, E.S., Araújo, J.E., Effect of surface treatment on the shear bond strength of a resin-based cement to porcelain (2006) Braz Dent J, 17, pp. 290-295Shimada, Y., Yamaguchi, S., Tagami, J., Micro-shear bond strength of dual-cured resin cement to glass ceramics (2002) Dent Mater, 18, pp. 380-388Chen, J.H., Matsumura, H., Atsuta, M., Effect of different etching periods on the bond strength of a composite resin to a machinable porcelain (1998) J Dent, 26, pp. 53-58Guler, A.U., Yilmaz, F., Yenisey, M., Guler, E., Ural, C., Effect of acid etching time and a self-etching adhesive on the shear bond strength of composite resin to porcelain (2006) J Adhes Dent, 8, pp. 21-25Kasuya, K., Miyazaki, Y., Ogawa, N., Maki, K., Manabe, A., Itoh, K., Efficacy of experimental dual-cure resin cement for orthodontic direct bond system (2006) Orthod Waves, 65, pp. 107-111Meguro, D., Hayakawa, T., Kasai, K., Efficacy of using orthodontic adhesive resin in bonding and debonding characteristics of a calcium phosphate ceramic bracket (2006) Orthod Waves, 65, pp. 148-154Dall'igna, C.M., Marchioro, E.M., Spohr, A.M., Mota, E.G., Effect of curing time on the bond strength of a bracket-bonding system cured with a light-emitting diode or plasma arc light (2011) Eur J Orthod, 33, pp. 55-59Correr, A.B., Sinhoreti, M.A., Sobrinho, L.C., Tango, R.N., Schneider, L.F., Consani, S., Effect of the increase of energy density on Knoop hardness of dental composites light-cured by conventional QTH, LED and xenon plasma arc (2005) Braz Dent J, 16, pp. 218-224Cekic-Nagas, I., Egilmez, F., Ergun, G., The effect of irradiation distance on microhardness of resin composites cured with different light curing units (2010) Eur J Dent, 4, pp. 440-446Thind, B.S., Stirrups, D.R., Lloyd, C.H., A comparison of tungstenquartz- halogen, plasma arc and light-emitting diode light sources for the polymerization of an orthodontic adhesive (2006) Eur J Orthod, 28, pp. 78-82Filipov, I.A., Vladimirov, S.B., Residual monomer in a composite resin after light-curing with different sources, light intensities and spectra of radiation (2006) Braz Dent J, 17, pp. 34-38Park, J.K., Hur, B., Ko, C.C., García-Godoy, F., Kim, H.I., Kwon, Y.H., Effect of light-curing units on the thermal expansion of resin nanocomposites (2010) Am J Dent, 23, pp. 331-334Price, R.B., Labrie, D., Rueggeberg, F.A., Felix, C.M., Irraciance differences in the violet (405 nm) and blue (460 nm) spectral ranges among dental light-curing units (2010) J Esthet Restor Dent, 22, pp. 363-377Yen, T.W., Blackman, R.B., Baez, R.J., Effect of acid etching on the flexural strength of a feldspathic porcelain and a castable glass ceramic (1993) J Prosthet Dent, 70, pp. 224-233Reynolds, I.R., Composite filling materials as adhesives in orthodontics (1975) Br Dent J, 138, p. 83Rueggeberg, F., Contemporary issues in photocuring (1999) Compend Contin Educ Dent, (SUPPL.), pp. 4-15Olsen, M.E., Bishara, S.E., Boyer, D.B., Jakobsen, J.R., Effect of varying etching times on the bond strength of ceramic brackets (1996) Am J Orthod Dentofacial Orthop, 109, pp. 403-409Sant'anna, E.F., Monnerat, M.E., Chevitarese, O., Stuani, M.B., Bonding brackets to porcelain - in vitro study (2002) Braz Dent J, 3, pp. 191-196Canay, S., Hersek, N., Ertan, A., Effect of different acid treatments on a porcelain surface (2001) J Oral Rehabil, 28, pp. 95-10

Evaluation of the AR4 CMIP3 and the AR5 CMIP5 model and projections for precipitation in northeast Brazil

This article compares the sensitivity of IPCC CMIP3-AR4 and CMIP5-AR5 models used on the latest reports from the Intergovernmental Panel on Climate Change (IPCC) in representing the annual average variations (austral summer and autumn) on three regions in Northeastern Brazil (NNEB) for the periods 1979–2000 using the CMAP (Climatology Merged Analysis of Precipitation) data as reference. The three areas of NNEB chosen for this analysis were the semiarid, eastern, and southern regions. The EOF analysis was performed to investigate how the coupled models resolve the temporal variability of the spatial modes in the Tropical Atlantic Sea Surface Temperature (SST), which drives the interannual variations of the rainfall in the Northeastern Brazil. CMIP3-AR4 and CMIP5-AR5 models presented a good representation of the annual cycle of precipitation. Results from correlation and mean absolute error analysis indicate that both CMIP3 and CMIP5 models produce large errors and barely capture the interannual rainfall variance during austral summer and autumn in Northeast Brazil, this features is closely related to the poor representation of the modes of SST variability in the Tropical Atlantic Ocean. For the summer and autumn rainfall projections (2040–2070) in the semiarid region, there was no convergence between the CMIP3 and CMIP5 models. During the summer and autumn in the eastern sector, both the CMIP3 and CMIP5 models projected rainfall above the mean for the 2040–2070 period

Antisymmetric Tensor Fields in Randall Sundrum Thick Branes

In this article we study the issue of localization of the three-form field in a Randall-Sundrum-like scenario. We simulate our membrane by kinks embedded in D=5, describing the usual case (not deformed) and new models coming from a specific deformation procedure. The gravitational background regarded includes the dilaton contribution. We show that we can only localize the zero-mode of this field for a specific range of the dilaton coupling, even in the deformed case. A study about resonances is presented. We use a numerical approach for calculations of the transmission coefficients associated to the quantum mechanical problem. This gives a clear description of the physics involved in the model. We find in this way that the appearance of resonances is strongly dependent on the coupling constant. We study the cases $p=1,3$ and 5 for $\alpha=-1.75$ and $\alpha=-20$. The first value of $\alpha$ give us one resonance peak for $p=1$ and no resonances for $p=3,5$. The second value of $\alpha$ give us a very rich structure of resonances, with number deppending on the value of $p$.Comment: 7 pages, 3 figure

(Twisted) Toroidal Compactification of pp-Waves

The maximally supersymmetric type IIB pp-wave is compactified on spatial circles, with and without an auxiliary rotational twist. All spatial circles of constant radius are identified. Without the twist, an S$^1$ compactification can preserve 24, 20 or 16 supercharges. $T^2$ compactifications can preserve 20, 18 or 16 supercharges; $T^3$ compactifications can preserve 18 or 16 supercharges and higher compactifications preserve 16 supercharges. The worldsheet theory of this background is discussed. The T-dual and decompactified type IIA and M-theoretic solutions which preserve 24 supercharges are given. Some comments are made regarding the AdS parent and the CFT description.Comment: 22 pages REVTeX 4 and AMSLaTeX. v3: References and a paragraph on nine dimensional Killing spinors were added. v4: A few typos corrected and a footnote was modifie

Enantioselective Synthesis, DFT Calculations, and Preliminary Antineoplastic Activity of Dibenzo 1-Azaspiro[4.5]decanes on Drug-Resistant Leukemias

The addition of 2-bromobenzylmagnesium bromide to chiral N-tert-butanesulfinyl imines derived from tetralone-type ketones proceeds with high levels of diastereocontrol. The resulting sulfinamide derivatives were transformed into dibenzoazaspiro compounds after a palladium-catalyzed intramolecular N-arylation. DFT calculations have been performed to rationalize the stereochemical course of the reaction. Similar results have been obtained considering either diethyl ether or toluene as a solvent, in both cases in an excellent agreement with experimental findings. NCI topological calculations have also been used to evidence crucial noncovalent interactions. In addition, the azaspiro compounds reduced the viability of chronic myeloid leukemia cells in the micromolar range. Notably, both the halogen-substituted (R)- and (S)-8g and -8h as well as (R)-8j were at least two times more effective on a multidrug-resistant derivative than on the parental cell line, exerting a collateral sensitivity effect.We acknowledge the continued financial support from the Spanish Ministerio de Economía y Competitividad (MINECO; project CTQ2014-53695-P, CTQ2014-51912-REDC, CTQ2016-81797-REDC, CTQ2016-76155-R, CTQ2017-85093-P), FEDER, the Generalitat Valenciana (PROMETEOII/2014/017), and the University of Alicante. We thankfully acknowledge the resources from the supercomputers “Memento” and “Cierzo” and technical expertise and assistance provided by BIFI-ZCAM (Universidad de Zaragoza, Spain). We also thank Prof. Vivian M. Rumjanek for providing FEPS cells and Prof. Adriano D. Andricopulo for the preliminary cytotoxicity screening. This study was also financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001

Ligand-Free Palladium-Catalyzed Oxyarylation of Dihydronaphthal­enes and Chromenequinone with o-Iodophenols and 3-Iodolawsone in PEG-400: An Efficient Synthesis of 5-Carbapterocarpans and Pterocarpanquinones

Dihydronaphthalenes were oxyarylated with o-iodophenols, in PEG-400 at 140 or 170 °C, leading regio- and stereoselectively to 5-carbapterocarpans. By using Pd(OAc)2 (5–10 mol%) as precatalyst and Ag2CO3 (1.1 equiv) as base (conditions A), products were obtained in good to excellent chemical yields, in 5–30 minutes, irrespective of the pattern of substitution the starting materials. Alternatively, when p-hydroxyacetophenone oxime derived palladacycle (1 mol%) was used as precatalyst, and dicyclohexylamine (2 equiv) was used as base (silver-free, conditions B), the corresponding adducts were obtained in moderate to good yields, in 0.5 to 4 hours. Finally, the oxyarylation of dihydronaphthalenes­ and chromenquinone with o-iodophenols and 3-iodolawsone in PEG-400 under conditions A led regio- and stereoselectively to the formation of carbapterocarpanquinones and pterocarpanquinones in moderate yield.Financial support from Brazilian agencies CAPES-DGU (Project 200/09), CNPq, FAPERJ and UFRJ are acknowledged. Spanish MICINN (Projects PHB2008-0037-PC, CTQ2007-62771/BQU, CTQ2010-20387, Consolider INGENIO 2010 CSD2007-00006), FEDER, Generalitat Valenciana (Project PROMETEO/2009/038), and the University of Alicante are acknowledged

Antitumoral, antileishmanial and antimalarial activity of pentacyclic 1,4-naphthoquinone derivatives

Pterocarpanquinones 8a-c, previously synthesized in our laboratory, and an homologous series of derivatives, compounds 9a-c prepared in this work, were evaluated on breast cancer cells (MCF-7) and on the parasites Leishmania amazonensis and Plasmodium falciparum, in culture. Compounds 8a-c were more potent than 9a-c on tumor cells and Leishmania amazonensis. On the other hand, 9a-c showed to be more active on Plasmodium falciparum. All the compounds studied were bioselective, presenting negligible cytotoxicity against fresh murine lymphocytes and human lymphocytes activated by the mitogen phytohemaglutinin (PHA)

Copper- versus palladium-catalyzed aromatization of 2-(methoxycarbonyl) tetralones: synthesis of methyl 1-hydroxy-2-naphthoates

The aromatization of α-tetralones substituted at the β-position by an ester group is reported using either CuI or Pd2(dba)3. In the case of using CuI (10 mol %) as catalyst and Cs2CO3 as base in dioxane, 2-(methoxycarbonyl)-α-tetralones are smoothly converted into the corresponding methyl 1-hydroxy-2-naphthoates at 70 °C under air. Alternatively, Pd2(dba)3 (1.25 mol %) can also be used as catalyst in the presence of K3PO4 as base in toluene also at 70 °C under argon. These are the most straightforward methodologies for the aromatization of these types of α-tetralones. CuI is the catalyst of choice due to higher efficiency, economical and practical reasons.The Spanish Ministerio de Ciencia e Innovación (MICINN) (projects CTQ2010-20387, and Consolider Ingenio 2010, CSD2007-00006), the Spanish Ministerio de Economia y Competitividad (MINECO) (projects CTQ2013-43446-P and CTQ2014-51912-REDC), the Generalitat Valenciana (PROMETEO 2009/039 and PROMETEOII/2014/017) and the University of Alicante are gratefully acknowledged for financial support. Financial support from Brazilian agencies: CAPES-DGU (Project 200/09), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (BJT-2014), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (PVE-2015), Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro and UFRJ is also acknowledged