Reinventing the De Mayo reaction: synthesis of 1,5-diketones or 1,5-ketoesters via visible light [2+2] cycloaddition of beta-diketones or beta-ketoesters with styrenes

[EN] A visible light mediated De Mayo reaction between 1,3-diketones and styrenes following a [2+2] cycloaddition pathway via a photosensitization mechanism gives access to 1,5-diketones. The reaction has been applied to substituted styrenes and aryl- and alkyl-substituted ketones. Moreover, the method converts -ketoesters, -amido esters, and -cyano ketones. Seven membered rings, a frequent structural motif of natural products, are also accessible using this methodology.This work was supported by the Deutsche Forschungsgemein-schaft DFG (GRK 1626, Chemical Photocatalysis). L. M. thanks the Alexander von Humboldt foundation for a postdoctoral fellowship. R. M.-H. thanks the DAAD for a short-term research grant. We thank Ms Regina Hoheisel (University of Regensburg) for her assistance in cyclic voltammetry measurements.Martínez-Haya, R.; Marzo, L.; König, B. (2018). Reinventing the De Mayo reaction: synthesis of 1,5-diketones or 1,5-ketoesters via visible light [2+2] cycloaddition of beta-diketones or beta-ketoesters with styrenes. Chemical Communications. 54(82):11602-11605. https://doi.org/10.1039/c8cc07044jS11602116055482Mayo, P. D., & Takeshita, H. (1963). PHOTOCHEMICAL SYNTHESES: 6. THE FORMATION OF HEPTANDIONES FROM ACETYLACETONE AND ALKENES. Canadian Journal of Chemistry, 41(2), 440-449. doi:10.1139/v63-061Begley, M. J., Mellor, M., & Pattenden, G. (1983). New synthetic approaches to fused-ring carbocycles based on intramolecular photocycloadditions of 1,3-dione enol esters. Journal of the Chemical Society, Perkin Transactions 1, 1905. doi:10.1039/p19830001905Oppolzer, W. (1982). The intramolecular [2 + 2] photoaddition/cyclobutane-fragmentation sequence in organic synthesis. Accounts of Chemical Research, 15(5), 135-141. doi:10.1021/ar00077a002Crimmins, M. T. (1988). Synthetic applications of intramolecular enone-olefin photocycloadditions. Chemical Reviews, 88(8), 1453-1473. doi:10.1021/cr00090a002Kärkäs, M. D., Porco, J. A., & Stephenson, C. R. J. (2016). Photochemical Approaches to Complex Chemotypes: Applications in Natural Product Synthesis. Chemical Reviews, 116(17), 9683-9747. doi:10.1021/acs.chemrev.5b00760Winkler, J. D., Rouse, M. B., Greaney, M. F., Harrison, S. J., & Jeon, Y. T. (2002). The First Total Synthesis of (±)-Ingenol. Journal of the American Chemical Society, 124(33), 9726-9728. doi:10.1021/ja026600aWinkler, J. D., Muller, C. L., & Scott, R. D. (1988). A new method for the formation of nitrogen-containing ring systems via the intramolecular photocycloaddition of vinylogous amides. A synthesis of mesembrine. Journal of the American Chemical Society, 110(14), 4831-4832. doi:10.1021/ja00222a053Winkler, J. D., Scott, R. D., & Williard, P. G. (1990). Asymmetric induction in the vinylogous amide photocycloaddition reaction. A formal synthesis of vindorosine. Journal of the American Chemical Society, 112(24), 8971-8975. doi:10.1021/ja00180a049Winkler, J. D., Bowen, C. M., & Liotta, F. (1995). [2 + 2] Photocycloaddition/Fragmentation Strategies for the Synthesis of Natural and Unnatural Products. Chemical Reviews, 95(6), 2003-2020. doi:10.1021/cr00038a010Y.-J. Wu , in Name Reactions for Carbocyclic Ring Formations , ed. J. J. Li , John Wiley & Sons, Inc. , Hoboken, New Jersey , 2010 , ch. 5, pp. 451–488A. C. Weedon , in CRC Handbook of Organic Photochemistry and Photobiology , ed. W. M. Horspool and P.-S. Song , CRC Press , Boca Raton , 1995 , pp. 670–684Ravelli, D., Protti, S., & Fagnoni, M. (2016). Carbon–Carbon Bond Forming Reactions via Photogenerated Intermediates. Chemical Reviews, 116(17), 9850-9913. doi:10.1021/acs.chemrev.5b00662Skubi, K. L., Blum, T. R., & Yoon, T. P. (2016). Dual Catalysis Strategies in Photochemical Synthesis. Chemical Reviews, 116(17), 10035-10074. doi:10.1021/acs.chemrev.6b00018Goddard, J.-P., Ollivier, C., & Fensterbank, L. (2016). Photoredox Catalysis for the Generation of Carbon Centered Radicals. Accounts of Chemical Research, 49(9), 1924-1936. doi:10.1021/acs.accounts.6b00288Yoon, T. P. (2016). Photochemical Stereocontrol Using Tandem Photoredox–Chiral Lewis Acid Catalysis. Accounts of Chemical Research, 49(10), 2307-2315. doi:10.1021/acs.accounts.6b00280Margrey, K. A., & Nicewicz, D. A. (2016). A General Approach to Catalytic Alkene Anti-Markovnikov Hydrofunctionalization Reactions via Acridinium Photoredox Catalysis. Accounts of Chemical Research, 49(9), 1997-2006. doi:10.1021/acs.accounts.6b00304Staveness, D., Bosque, I., & Stephenson, C. R. J. (2016). Free Radical Chemistry Enabled by Visible Light-Induced Electron Transfer. Accounts of Chemical Research, 49(10), 2295-2306. doi:10.1021/acs.accounts.6b00270Ghosh, I., Marzo, L., Das, A., Shaikh, R., & König, B. (2016). Visible Light Mediated Photoredox Catalytic Arylation Reactions. Accounts of Chemical Research, 49(8), 1566-1577. doi:10.1021/acs.accounts.6b00229Meggers, E. (2015). Asymmetric catalysis activated by visible light. Chemical Communications, 51(16), 3290-3301. doi:10.1039/c4cc09268fGuo, L.-N., Wang, H., & Duan, X.-H. (2016). Recent advances in catalytic decarboxylative acylation reactions via a radical process. Organic & Biomolecular Chemistry, 14(31), 7380-7391. doi:10.1039/c6ob01113fMarzo, L., Pagire, S. K., Reiser, O., & König, B. (2018). Visible-Light Photocatalysis: Does It Make a Difference in Organic Synthesis? Angewandte Chemie International Edition, 57(32), 10034-10072. doi:10.1002/anie.201709766Lu, Z., & Yoon, T. P. (2012). Visible Light Photocatalysis of [2+2] Styrene Cycloadditions by Energy Transfer. Angewandte Chemie International Edition, 51(41), 10329-10332. doi:10.1002/anie.201204835Mojr, V., Svobodová, E., Straková, K., Neveselý, T., Chudoba, J., Dvořáková, H., & Cibulka, R. (2015). Tailoring flavins for visible light photocatalysis: organocatalytic [2+2] cycloadditions mediated by a flavin derivative and visible light. Chemical Communications, 51(60), 12036-12039. doi:10.1039/c5cc01344ePagire, S. K., Hossain, A., Traub, L., Kerres, S., & Reiser, O. (2017). Photosensitised regioselective [2+2]-cycloaddition of cinnamates and related alkenes. Chemical Communications, 53(89), 12072-12075. doi:10.1039/c7cc06710kZhao, J., Brosmer, J. L., Tang, Q., Yang, Z., Houk, K. N., Diaconescu, P. L., & Kwon, O. (2017). Intramolecular Crossed [2+2] Photocycloaddition through Visible Light-Induced Energy Transfer. Journal of the American Chemical Society, 139(29), 9807-9810. doi:10.1021/jacs.7b05277Hörmann, F. M., Chung, T. S., Rodriguez, E., Jakob, M., & Bach, T. (2018). Evidence for Triplet Sensitization in the Visible‐Light‐Induced [2+2] Photocycloaddition of Eniminium Ions. Angewandte Chemie International Edition, 57(3), 827-831. doi:10.1002/anie.201710441Alonso, R., & Bach, T. (2014). A Chiral Thioxanthone as an Organocatalyst for Enantioselective [2+2] Photocycloaddition Reactions Induced by Visible Light. Angewandte Chemie International Edition, 53(17), 4368-4371. doi:10.1002/anie.201310997Blum, T. R., Miller, Z. D., Bates, D. M., Guzei, I. A., & Yoon, T. P. (2016). Enantioselective photochemistry through Lewis acid–catalyzed triplet energy transfer. Science, 354(6318), 1391-1395. doi:10.1126/science.aai8228Miller, Z. D., Lee, B. J., & Yoon, T. P. (2017). Enantioselective Crossed Photocycloadditions of Styrenic Olefins by Lewis Acid Catalyzed Triplet Sensitization. Angewandte Chemie International Edition, 56(39), 11891-11895. doi:10.1002/anie.201706975Hanss, D., Freys, J. C., Bernardinelli, G., & Wenger, O. S. (2009). Cyclometalated Iridium(III) Complexes as Photosensitizers for Long-Range Electron Transfer: Occurrence of a Coulomb Barrier. European Journal of Inorganic Chemistry, 2009(32), 4850-4859. doi:10.1002/ejic.200900673Prier, C. K., Rankic, D. A., & MacMillan, D. W. C. (2013). Visible Light Photoredox Catalysis with Transition Metal Complexes: Applications in Organic Synthesis. Chemical Reviews, 113(7), 5322-5363. doi:10.1021/cr300503rTeegardin, K., Day, J. I., Chan, J., & Weaver, J. (2016). Advances in Photocatalysis: A Microreview of Visible Light Mediated Ruthenium and Iridium Catalyzed Organic Transformations. Organic Process Research & Development, 20(7), 1156-1163. doi:10.1021/acs.oprd.6b00101Flamigni, L., Barbieri, A., Sabatini, C., Ventura, B., & Barigelletti, F. (s. f.). Photochemistry and Photophysics of Coordination Compounds: Iridium. Topics in Current Chemistry, 143-203. doi:10.1007/128_2007_131Luo, J., & Zhang, J. (2016). Donor–Acceptor Fluorophores for Visible-Light-Promoted Organic Synthesis: Photoredox/Ni Dual Catalytic C(sp3)–C(sp2) Cross-Coupling. ACS Catalysis, 6(2), 873-877. doi:10.1021/acscatal.5b02204Fukuzumi, S., & Ohkubo, K. (2014). Organic synthetic transformations using organic dyes as photoredox catalysts. Org. Biomol. Chem., 12(32), 6059-6071. doi:10.1039/c4ob00843jRomero, N. A., & Nicewicz, D. A. (2016). Organic Photoredox Catalysis. Chemical Reviews, 116(17), 10075-10166. doi:10.1021/acs.chemrev.6b00057Ni, T., Caldwell, R. A., & Melton, L. A. (1989). The relaxed and spectroscopic energies of olefin triplets. Journal of the American Chemical Society, 111(2), 457-464. doi:10.1021/ja00184a008Xie, Z.-F., Suemune, H., & Sakai, K. (1989). A Facile Ring Enlargement. Synthetic Communications, 19(5-6), 987-992. doi:10.1080/00397918908051019Li, C.-J., Chen, D.-L., Lu, Y.-Q., Haberman, J. X., & Mague, J. T. (1998). Metal-mediated two-atom carbocycle enlargement in aqueous medium. Tetrahedron, 54(11), 2347-2364. doi:10.1016/s0040-4020(98)00004-0Hong, B.-C., Chen, S.-H., Kumar, E. S., Lee, G.-H., & Lin, K.-J. (2003). Intramolecular [2+2] Photocycloaddition-Fragmentation: Facile Entry to a Novel Tricyclic 5-6-7 Ring System. Journal of the Chinese Chemical Society, 50(4), 917-926. doi:10.1002/jccs.200300129Roscini, C., Davies, D. M. E., Berry, M., Orr-Ewing, A. J., & Booker-Milburn, K. I. (2008). Product Selection through Photon Flux: Laser-Specific Lactone Synthesis. Angewandte Chemie International Edition, 47(12), 2283-2286. doi:10.1002/anie.200704816Tobita, S., Ohba, J., Nakagawa, K., & Shizuka, H. (1995). Recovery mechanism of the reaction intermediate produced by photoinduced cleavage of the intramolecular hydrogen bond of dibenzoylmethane. Journal of Photochemistry and Photobiology A: Chemistry, 92(1-2), 61-67. doi:10.1016/1010-6030(95)04158-xMoriyasu, M., Kato, A., & Hashimoto, Y. (1986). Kinetic studies of fast equilibrium by means of high-performance liquid chromatography. Part 11. Keto–enol tautomerism of some β-dicarbonyl compounds. J. Chem. Soc., Perkin Trans. 2, (4), 515-520. doi:10.1039/p29860000515Casey, B. M., Eakin, C. A., Jiao, J., Sadasivam, D. V., & Flowers, R. A. (2009). Solvent-dependent oxidative coupling of 1-aryl-1,3-dicarbonyls and styrene. Tetrahedron, 65(52), 10762-10768. doi:10.1016/j.tet.2009.06.118Ko, T. Y., & Youn, S. W. (2016). Cooperative Indium(III)/Silver(I) System for Oxidative Coupling/Annulation of 1,3-Dicarbonyls and Styrenes: Construction of Five-Membered Heterocycles. Advanced Synthesis & Catalysis, 358(12), 1934-1941. doi:10.1002/adsc.201600280Casals, P.-F., Ferard, J., & Ropert, R. (1976). Photoaddition de dicetones-1,3 aromatiques sur divers carbures styreniques : orientation et stereospecificite de l’addition. Tetrahedron Letters, 17(35), 3077-3080. doi:10.1016/0040-4039(76)80074-3Kikuchi, A., Oguchi, N., & Yagi, M. (2009). Optical and Electron Paramagnetic Resonance Studies of the Excited States of 4-tert-Butyl-4′-Methoxydibenzoylmethane and 4-tert-Butyl-4′-Methoxydibenzoylpropane. The Journal of Physical Chemistry A, 113(48), 13492-13497. doi:10.1021/jp905236mTurro, N. J. (1966). Triplet-triplet excitation transfer in fluid solution: Applications to organic photochemistry. Journal of Chemical Education, 43(1), 13. doi:10.1021/ed043p13Dilling, W. L. (1969). Photochemical cycloaddition reactions of nonaromatic conjugated hydrocarbon dienes and polyenes. Chemical Reviews, 69(6), 845-877. doi:10.1021/cr60262a005N. J. Turro , in Modern Molecular Photochemistry , Benjamin/Cummings , California , 1978 , ch. 9, pp. 296–359Albini, A. (1981). Photosensitization in Organic Synthesis. Synthesis, 1981(04), 249-264. doi:10.1055/s-1981-29405Kalyanasundaram, K. (1982). Photophysics, photochemistry and solar energy conversion with tris(bipyridyl)ruthenium(II) and its analogues. Coordination Chemistry Reviews, 46, 159-244. doi:10.1016/0010-8545(82)85003-0Juris, A., Balzani, V., Barigelletti, F., Campagna, S., Belser, P., & von Zelewsky, A. (1988). Ru(II) polypyridine complexes: photophysics, photochemistry, eletrochemistry, and chemiluminescence. Coordination Chemistry Reviews, 84, 85-277. doi:10.1016/0010-8545(88)80032-8Cismesia, M. A., & Yoon, T. P. (2015). Characterizing chain processes in visible light photoredox catalysis. Chemical Science, 6(10), 5426-5434. doi:10.1039/c5sc02185

Smoking Habits Among Patients Diagnosed with Oral Lichen Planus

<p>Abstract</p> <p>Introduction</p> <p>Oral lichen planus (OLP) is one of the most common dermatologic diseases that manifests in the oral cavity. The purpose of this study was to evaluate the association between smoking habits and the clinical subtypes of OLP.</p> <p>Methods</p> <p>Oral findings and smoking data from 187 charts of OLP patients from an oral medicine clinic was reviewed and compared to data from 76 matched control patients.</p> <p>Results and Discussion</p> <p>Ninety-three patients were diagnosed with reticular OLP, 55 with atrophic and 39 with erosive forms of the disease. Symptomatic OLP occurred in 63.6% of patients. Fewer cases of reticular OLP were symptomatic than erosive OLP (p < 0.001). Significantly fewer OLP patients smoked than the control group (16% versus 25%) (p = 0.04). More patients with reticular OLP smoked than those with atrophic and erosive OLP (p = 0.002). It is hypothesized that the heat and irritation of smoking may aggravate symptomatic OLP lesions, and the risk of malignant transformation associated with tobacco use may play a role in patients stopping tobacco use. Because there were fewer smokers in patients with OLP, and because OLP carries an increased malignant risk, transformation of OLP may be due to a different etiology and of a different pathogenesis than squamous cell carcinoma not arising from lichen planus. Close follow-up of patients with OLP is indicated.</p

Early Inititation of Breastfeeding and Vitamin a Supplementation with Nutritional Status of Children Aged 6-59 Months

Toddler period, especially the first two years of life is considered as golden age for children because of their rapid growth and development. Therefore, the occurrence of nutritional disorders in the period can be permanent and irreversible. This study tried to assess correlation between early initiation of breastfeeding and vitamin A with nutritional status. The total of samples analyzed in this study was 1,592 toddlers aged 6-59 months that were drawn from 2015 Indonesia Nutritional Status Monitoring Survey in Bengkulu. Data including age, sex, early initiation of breastfeeding, birth length, birth weight, vitamin A supplementation were collected by using questionnaire. Weight and height of children were obtained through anthropometric measurements. More than half of the toddlers (54.6%) did not get early initiation of breastfeeding. Based on multivariate analysis results, most dominant variables related to weight/age, height/age and weight/height indicators were early initiation of breastfeeding and Vitamin A supplementation. Toddlers who did not get early initiation of breastfeeding are at risk of 1.555 times stunting compared to toddlers who got early initiation of breastfeeding. The most dominant variable related to height/age isvitamin A supplementation. Children who do not get vitamin A supplementation are at risk of stunting 2.402 times compared to children who get vitamin A supplementation

Antenatal Care Practice and the Chance of Having Nurse/midwife Birth Attendant: a Study in Central Mountain of Papua

Background: Papua has one of the highest maternal mortality rates in Indonesia. Nurse/midwife birth attendants and regular antenatal care (ANC) are important factors in decreasing maternal mortality rate. This study aimed to identify the association of ANC to nurse/midwife-assisted birth in Papua.Methods: The subjects of this cross-sectional study and purposive sampling consisted of females with toddlers in the family visiting the integrated community center on 15-30 January 2014 in 24 villages in Central Mountain of Jayawijaya, Papua. Several demographic characteristics, ANC practices, and labor practices were collected by interview. Analysis was carried out by Cox regression with constant time.Results: There were 469 subjects, but only 391 subjects were available for analysis which consisted of 280 subjects with self/family-assisted births and 111 with nurse/midwife-assistedbirths. There were only 3 subjects that gave birth in the forest or stable (“kandang hina”). Compared with those who never had ANC, those who had ANC in the integrated community center had 5.6-fold possibility to have a nurse/ midwife-assisted birth [adjusted relative risk (RRa) = 5.60; 95% confidence interval (CI) = 2.99-10.47]. In addition, compared with those who never had ANC, those who had ANC by midwife and 4 ANC visits had higher possibility to have nurse/midwife-assisted birth, 4.9-fold (RRa = 4.89; 95% CI = 2.70-8.86) and 6.9-fold (RRa = 6.90; 95% CI = 3.59-13.27) respectively.Conclusion: Antenatal care service is a possible way to increase the proportion of deliveries by nurse/midwife in Central Mountain of Jayawijaya, Papua. (Health Science Indones 2014;2:60-6

Four problems with global carbon markets: a critical review

This article offers a critique of global carbon markets and trading, with a special focus on the Clean Development Mechanism of the Kyoto Protocol. It explores problems with the use of tradable permits to address climate change revolving around four areas: homogeneity, justice, gaming, and information. Homogeneity problems arise from the non-linear nature of climate change and sensitivity of emissions, which complicate attempts to calculate carbon offsets. Justice problems involve issues of dependency and the concentration of wealth among the rich, meaning carbon trading often counteracts attempts to reduce poverty. Gaming problems include pressures to promote high-volume, least-cost projects and the consequences of emissions leakage. Information problems encompass transaction costs related to carbon trading and market participation and the comparatively weak institutional capacity of project evaluators

Freezing of hard spheres confined in narrow cylindrical pores

Monte Carlo simulations for the equation of state and phase behavior of hard spheres confined inside very narrow hard tubes are presented. For pores whose radii are greater than 1.1 hard sphere diameters, a sudden change in the density and the microscopic structure of the fluid is neatly observed, indicating the onset of freezing. In the high-density structure the particles rearrange in such a way that groups of three particles fit in sections across the por

Studies on vascular response to full superantigens and superantigen derived peptides:Possible production of novel superantigen variants with less vasodilation effect for tolerable cancer immunotherapy

Superantigens (SAgs) are a class of antigens that cause non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release and causing symptoms similar to sepsis, e.g. hypotension and subsequent hyporeactivity. We investigated the direct effect of SAgs on vascular tone using two recombinant SAgs, SEA and SPEA. The roles of Nitric Oxide (NO) and potentially hyperpolarization, which is dependent on the K + channel activation, were also explored. The data show that SEA and SPEA have direct vasodilatory effects that were in part NO-dependent, but completely dependent on activation of K + channels. Our work also identified the functional regions of one of the superantigens, SPEA, that are involved in causing the vasodilation and possible hypotension. A series of 20 overlapping peptides, spanning the entire sequence of SPEA, were designed and synthesized. The vascular response of each peptide was measured, and the active peptides were identified. Our results implicate the regions, (61–100), (101–140) and (181–220) which cause the vasodilation and possible hypotension effects of SPEA. The data also shows that the peptide 181–220 exert the highest vasodilation effect. This work therefore, demonstrates the direct effect of SAgs on vascular tone and identify the active region causing this vasodilation. We propose that these three peptides could be effective novel antihypertensive drugs. We also overexpressed, in E.coli, four superantigens from codon optimized genes

Computer simulation study of the nematic–vapour interface in the Gay–Berne model

We present computer simulations of the vapour–nematic interface of the Gay–Berne model. We considered situations which correspond to either prolate or oblate molecules. We determine the anchoring of the nematic phase and correlate it with the intermolecular potential parameters. On the other hand, we evaluate the surface tension associated to this interface. We find a corresponding states law for the surface tension dependence on the temperature, valid for both prolate and oblate molecules.Fundación Portuguesa para la Ciencia y la Tecnología EXCL / FIS-NAN / 0083/2012Ministerio de Economía y Competitividad FIS2012-32455Junta de Andalucía P09-FQM-493

Metabolomics Approaches for the Diagnosis, Treatment, and Better Disease Management of Viral Infections

Metabolomics is an analytical approach that involves profiling and comparing the metabolites present in biological samples. This scoping review article offers an overview of current metabolomics approaches and their utilization in evaluating metabolic changes in biological fluids that occur in response to viral infections. Here, we provide an overview of metabolomics methods including high-throughput analytical chemistry and multivariate data analysis to identify the specific metabolites associated with viral infections. This review also focuses on data interpretation and applications designed to improve our understanding of the pathogenesis of these viral diseases.This research was funded by the Qatar National Research Fund (QNRF), grant number (NPRP11S-1212-170092).Scopu