2011-2015
Publicação 55
Basic Concepts and Applications of Porphyrins, Chlorins and Phthalocyanines as Photosensitizers in Photonic Therapies
Oliveira, K. T.; Souza, J. M.; Gobo, N. R. S; Assis, F. F; Brocksom, T. J. RVQ, v. 7, p. 310-335, 2015.
DOI: 10.5935/1984-6835.20150016
Abstract
Nesta revisão são descritas algumas aplicações da luz em terapias fotônicas, em particular, na terapia fotodinâmica (PDT) que envolve a combinação luz/fotossensibilizador/oxigênio. Foram selecionados e apresentados alguns exemplos mais relevantes dos derivados do tipo porfirina, clorina e ftalocianina que são atualmente comercializados como fotossensibilizadores para uso nesta terapia. O objetivo aqui não é cobrir todas as alternativas de fotossensibilizadores no mercado nem mesmo em fase de estudos acadêmicos, e sim, dar uma visão geral sobre fotossensibilizadores e PDT dentro da perspectiva de como ocorre a interação da luz com a matéria.
Publicação 54
A Practical Deca-gram Scale Ring Expansion of (R)-(-)-carvone to (R)-(+)-3-methyl-6-isopropenyl-cyclohept-3-enone-1.
Alves, L. C; Desiderá, A. L; de Oliveira, K. T; Newton, S; Ley, S. V; Broncksom, T. J. Org Biomol Chem. v.13, p. 7633-7642, 2015.
Abstract
A route to enantiopure (R)-(+)-3-methyl-6-isopropenyl-cyclohept-3-enone-1, an intermediate for terpenoids, has been developed and includes a highly chemo- and regioselective Tiffeneau–Demjanov reaction. Starting from readily available (R)-(−)-carvone, this robust sequence is available on a deca-gram scale and uses flow chemistry for the initial epoxidation reaction. The stereochemistry of the addition of two nucleophiles to the carbonyl group of (R)-(−)-carvone has been determined by X-ray diffraction studies and chemical correlation.
Publicação 53
Selective Vilsmeier-Haack aryl-formylations of tetrathienylporphyrin and its Ni(II) complex
Momo, P. B.; Sampaio, O. M.; Brocksom, T. J; de Oliveira, K. T. J Porphyr Phthalocya, v. 19, p. 745-752, 2015.
DOI: http://dx.doi.org/10.1142/S1088424615500467
Abstract
Regioselective aryl-formylations of tetrathienylporphyrin and its Ni(II) complex were performed with the Vilsmeier–Haack reaction. We have studied different solvents and temperatures to obtain the mono, di, tri and tetra-formylated porphyrins, all at the α-position of the thienyl groups. No β-formylations were observed and the four different formylated products presented here are suitable intermediates for subsequent extended conjugation reactions.
Publicação 52
The New Directions of Organic Synthesis.
Brocksom, T. J.; Desiderá, A; Alves, L .C. ; Oliveira, K. T, Curr Org Synth. v. 12, p. 496-522, 2015.
DOI: 10.2174/157017941205150821121222
Abstract
This review deals with the important changes that have taken place in the last twenty to thirty years, on the directions and objectives of organic synthesis. Target oriented synthesis now competes with diversity oriented synthesis, and variations, in an attempt to occupy chemical space more completely. At the same time practicality, efficiency, scalability and robustness are once again the major goals to be associated with atom, step and function economies, within the context of sustainability.
Publicação 51
Exploiting Novel Process Windows for the Synthesis of meso-Substituted Porphyrins under Continuous Flow Conditions
Momo, P. B; Bellete, B. S;Brocksom, T. J.; de Souza, R. O. M. A; de Oliveira, K. T. RSC Adv, v. 5, p. 84350-84355, 2015.
Abstract
Porphyrin synthesis by classical methods frequently involves the use of high temperatures, toxic and dangerous reagents yielding the product in very low amounts and with poor scalability. Herein, we have studied the synthesis of meso-substituted porphyrins under continuous flow conditions, thus demonstrating scale-up for the porphyrin synthesis in a safe, cost-competitive, highly pure, reproducible and robust manner.
Publicação 50
Oxime derivatives with larvicidal activity against Aedes aegypti L
Lima, T. C; Santos, S. R. L; Uliana, M. P; La Corte Santos, R; Brocksom, T. J; de Holanda Cavalcanti, S. C; de Souza,D. P. Parasitol Res , v. 114, p. 2883-2891, 2015.
DOI: 10.1007/s00436-015-4489-9
Abstract
Oximes containing secondary metabolites constitute an important group of bioactive compounds and have been described and frequently updated in the literature due to their pharmacological properties. Thus, the aim of this study was to evaluate the larvicidal activity of a series of fourteen structurally related [1,4]-Benzoquinone mono-oximes on third-instar Aedes aegypti larvae and to investigate structure-activity relationships (SAR) of these compounds. Results of larvicidal assay revealed that all oximes were found to have larvicidal activity. Compound 2,6-dimethyl-[1,4]-benzoquinone oxime tosylate (11) was the most bioactive (LC50 = 9.858 ppm), followed by 2-methyl-[1,4]-benzoquinone oxime tosylate (9) (LC50 = 14.450 ppm). [1,4]-benzoquinone oxime (1) exhibited the lowest potency, with an LC50 = 121.181 ppm. The molecular characteristics which may help to understand the assayed compounds larvicidal activity were identified. SAR indicates that the addition of alkyl groups attached to the ring, number, position in the unsaturated cyclic structure, and size of these groups influence the larvicidal activity. Moreover, the lipophilicity seems to play an important role in increasing the larvicidal effect, because, in general, tosyl-containing products were more potent than products containing free OH.
Publicação 49
NIR bacteriochlorin chromophores accessed by Heck and Sonogashira cross-coupling reactions on a tetrabromobacteriochlorin derivative.
de Assis, F. F.; Ferreira, M. A. B ; Brocksom, T. J; de Oliveira, K, T. Org Biomol Chem, v. 14, p. 1402-1412, 2015.
Abstract
The synthesis of a new tetrabromobacteriochlorin BCBr4 is reported having the 3,4-dibromo-1H-pyrrole-2-carbaldehyde (10) as the major precursor. The BCBr4 was successfully employed in Pd cross-coupling reactions with methyl acrylate, phenyl acetylene and 4-ethynylanisole. In all three cases, the desired tetra-coupled products were obtained in good to excellent yields, and present a significant red shift in the UV-Vis bands above 800 nm. DFT and TD-DFT theoretical analyses of the NIR bacteriochlorin chromophores were performed in order to evaluate the effect of β substitution on their electronic structures.
Publicação 48
“Synthesis of non-aggregating chlorins and isobacteriochlorins from meso-tetrakis(pentafluorophenyl)porphyrin: a study using 1,3-dipolar cycloadditions under mild conditions”
De Souza, J. M. ; de Assis, F. F. ; Carvalho, C. M.B. ; Cavaleiro, J. A.S. ; Brocksom, T. J. ; de Oliveira, K. T. Tetrahedron Lett. 2014, 55, 1491-1495.
DOI: 10.1016/j.tetlet.2014.01.049
Abstract
The 1,3-dipolar cycloaddition of meso-tetrakis(pentafluorophenyl)porphyrin and its nickel complex, with the bulky azomethine ylide dipole was studied under mild conditions, and yielded chlorin and isobacteriochlorin derivatives self-prevented from aggregation. The reactions were performed at room temperature or 0 °C, and we were able to establish a set of reaction conditions to obtain only the chlorin or the isobacteriochlorin. These compounds were evaluated in solution, and no aggregation was observed at less than 25 mM (~30 mg mL-1) using 1H NMR experiments.
Publicação 47
“Solvent-free Diels-Alder reactions catalyzed by FeCl3 on Aerosil silica”
Donatoni, M. C. ; Junior, G. A.B. ; de Oliveira, K. T. ; Ando, R. A. ; Brocksom, T. J. ; Dos Santos, A. A. Tetrahedron. 2014, 70, 3231-3238.
DOI: 10.1016/j.tet.2014.02.017
Abstract
A mild solvent-free protocol for the promotion of the Diels–Alder reactions of simple dienes and p-benzoquinones, catalyzed by a mixture of iron(III) chloride on Aerosil® silica is reported.
Publicação 46
“Chlorins: Natural Sources, Synthetic Developments and Main Applications”
de Oliveira, K.T. ; Momo, P. B. ; de Assis, F. F. ; Ferreira, M. A. B. ; Brocksom, T. J. Curr. Org. Synth. 2014, 11, 42-58.
DOI: 10.2174/15701794113106660085
Abstract
Chlorin derivatives have attracted considerable attention over the last three decades in different scientific fields. These compounds are present in a large number of bacteria, fungi and in all plants found on Earth. Since the discovery of these pigments, chemists, biologists, medical professionals and materials scientists have devoted pronounced efforts in order to develop new synthetic methods and discover useful applications for these compounds. In this review we wish to cover the main natural chlorins, their natural sources, synthetic approaches to access these compounds, and the major applications.
Publicação 45
“Unequivocal structural assignments of three cycloheptenoid intermediates for guaiane sesquiterpenes: an experimental and theoretical approach”
Barbosa, L. R. ; Vieira, Y. W. ; Lacerda, V. ; de Oliveira, K. T. ; Dos Santos, R. B. ; Greco, S. J. ; Neto, A. C. ; De Castro, E. V. R. ; Brocksom, T. J. Magn. Reson. Chem. 2014, 52, n/a-n/a.
Abstract
Publicação 44
“Photobiological characteristics of chlorophyll a derivatives as microbial PDT agents”
Uliana, M. P. ; Pires, L. ; Pratavieira, S. ; Brocksom, T. J. ; de Oliveira, K. T. ; Bagnato, V. S. ; Kurachi, C. Photoch. Photobio. Sci. 2014, 13, n/a-n/a.
Abstract
Chlorin-e6 (chl-e6) and a hydrogenated derivative (chl-e6H) were semi-synthesized, and their photophysical properties and photodynamic activity against Escherichia coli, Staphylococcus aureus and Candida albicans evaluated. Methyl pheophorbide-a (Mepheo-a) was obtained from S. maxima using methanolic extraction with acid catalysis (CH3OH–H2SO4). Chlorin-e6 was prepared from Mepheo-a by basic hydrolysis with H2O–acetone and NaOH. Hydrogenated Chlorin-e6 was synthesized by a similar procedure starting from the hydrogenated methyl pheophorbide-a (Mepheo-aH). Photophysical studies were performed in order to determine the singlet oxygen quantum yield of chl-e6H which is higher than that of chl-e6. The microorganism inactivation of chl-e6 and chl-e6H was investigated at two concentrations and three fluence levels. Both chl-e6 and chl-e6H showed microorganism inactivation against Gram-positive bacteria and a fungus.
Publicação 43
“Tetrabenzoporphyrins: synthetic developments and applications”
Carvalho, C. M. B. ; Brocksom, T. J. ; de Oliveira, K. T. CHEM SOC REV, 2013, 42, 3302-3317.
Abstract
Tetrabenzoporphyrins have attracted considerable worldwide attention over the last few decades. Since the discovery of these pigments, chemists, biologists, medical professionals and material scientists have devoted pronounced efforts in order to develop synthetic methods and discover useful applications for these compounds. Nowadays, tetrabenzoporphyrins occupy a prominent position in porphyrin chemistry, and this review is intended to cover the main synthetic methods and applications of these compounds.
Publicação 42
‘Harvestman Phenols and Benzoquinones: Characterisation and Biosynthetic Pathway’
Rocha, D. F. O.; Wouters, F. C.; Zampieri, D. S.; Brocksom, T. J.; Machado, G.; Marsaioli, A. J. Molecules, 2013, 18, 11429-11451.
DOI: 10.3390/molecules180911429
Abstract:
Benzoquinones are usually present in arthropod defence exudates. Here, we describe the chemical profiles of 12 harvestman species belonging to the neotropical family Gonyleptidae. Nine of the studied species produced benzoquinones, while three produced alkyl phenols. Two benzoquinones and one phenol exhibited biological activity against bacteria and fungi. We also studied the biosynthesis of 2-ethyl-1,4-benzoquinone by feeding Magnispina neptunus individuals with ¹³C-labelled precursors; the benzoquinones were biosynthesised through a polyketide pathway using acetate and propionate building blocks.
Publicação 41
(+-)-(4aR,5R,8S,8aR)-8-(tert-Butyl-dimethylsilyloxy)-2,5,8a-Trimethyl-4a,5,8,8a-Tetrahydronaphthalene-1,4-Dione
Delling, F. N.; Zukerman-Schpector, J.; Brocksom, T. J.; Brocksom, U.; Finelli, F. G.; Tiekink, E. R. T. Acta Cryst. 2013, E69, o325.
DOI:
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Publicação 40
“Synthesis and photophysical studies of a chlorin sterically designed to prevent self-aggregation”
de Assis, F. F. ; de Souza, J. M. ; Assis, B. H.K. ; Brocksom, T. J. ; de Oliveira, K. T.
DYES PIGMENTS 2013, 98, 153-159.
DOI: 10.1016/j.dyepig.2013.02.011
Abstract
Synthesis and photophysical evaluations of a new non-aggregating chlorin derivative are described. A β-octa(carboxyethyl)porphyrin 3 was synthesized in 2 steps starting from pyrrole-3,4-dicarboxylic acid diethyl ester (2). The new chlorin derivative 6 was obtained through a 1,3-dipolar cycloaddition using benzyl azomethine ylide. Chlorin 6 presents a molecular scaffold in an “L” shape avoiding aggregation in solutions at 1–27 mM. Photophysical properties were measured, and indicate that this new compound can be considered a useful candidate for PDT studies.
Publicação 39
“Synthesis of functionalized chlorins sterically-prevented from self-aggregation”
dos Santos, F. A. B. ; Uchoa, A. F. ; Baptista, M. S. ; Iamamoto, Y. ; Serra, O. A. ; Brocksom, T. J. ; de Oliveira, K. T. DYES PIGMENTS, 2013, 99, 402-411.
DOI: 10.1016/j.dyepig.2013.05.024
Abstract
The synthesis of six new regioisomeric chlorin derivatives sterically-prevented from self-aggregation is described. The compounds were prepared by the Diels–Alder reaction between protoporphyrin IX dimethyl ester, and N-[p-(1,3-dithiolan)phenyl]maleimide and N-(p-formylphenyl)maleimide. The protopophyrin IX dimethyl ester was synthesized in 2 steps from natural hematoporphyrin using a modified procedure from literature, and the substituted maleimides were conveniently synthesized, aiming at producing formyl-chlorins for subsequent functionalization with amphiphilic groups. The Diels–Alder reactions were systematically studied in order to establish optimized conditions for the cycloadditions.
The regioisomers were fully characterized and the aggregation studies were performed by NMR, UV–Vis spectroscopy, and also HRMS (ESI-TOF and MALDI-TOF). Preliminary evaluations on the photosensitizing activities and amphiphilicity were carried out indicating that these new compounds are potential candidates, to be studied in more advanced tests of Photodynamic Therapy (PDT). This work represents on advance on our previous study, with respect to these new structures, their photophysical properties and amphiphilicity.
Publicação 38
“Synthesis of an Octa-tert-butylphthalocyanine: A Low-Aggregating and Photochemically Stable Photosensitizer”
Gobo, N. R. S. ; Brocksom, T. J. ; Zukerman-Schpector, J. ; de Oliveira, K. T. EUR J ORG CHEM 2013, 23, n/a-n/a.
Abstract
The synthesis of a new octa-tert-butylphthalocyanine is described. First, the 4,5-di-tert-butylphthalonitrile building block was synthesized in a six-step approach, in which the last step is a three reaction domino sequence. Then, this phthalonitrile was cyclotetramerized to furnish a new phthalocyanine dye, which presented no aggregation in solution and good photophysical properties.
Publicação 37
“Synthesis and photophysical evaluations of ß-fused uracil-porphyrin derivatives”
Carvalho, C. M. B. ; Fujita, M. A. ; Brocksom, T. J. ; de Oliveira, K. TETRAHEDRON, 2013, 69, 9986-9993.
DOI : 10.1016/j.tet.2013.09.069
Abstract
New β-fused uracil-porphyrin conjugates were synthesized by the tetramerization of uracil-pyrroles under acidic conditions. Two different synthetic approaches were systematically studied in order to evaluate their efficiency, as well as the possibility to obtain a single regioisomer. Metallation effects were studied for aggregation in solution, and preliminary photophysical experiments were also performed in order to evaluate the potential of these new compounds.
Publicação 36
Chemical Constituents of Essential Oils as Raw Materials in the Synthesis of Bioactive Compounds, in Medicinal Essential Oils: Chemical, Pharmacological, and Therapeutic Aspects
Brocksom, T. J.; Donatoni, M. C.; Uliana, M. P.; de Sousa, D. P. Nova Science Publishers ,2012, 3, 23-49
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Publicação 35
Antinociceptive Activity of Thymoquinone and its Structural Analogues: a Structure-Activity Relationships Study
De Sousa, D. P.; Nóbrega, F. F. F.; Santos, C. C. M. P.; Benedito, R. B.; Vieira, Y. W.; Uliana M. P.; Brocksom, T. J.; de Almeida, R. N. Tropical Journal of Pharmaceutical Research, 2012, 13, 605-610.
Abstract:
Purpose: To investigate the structural features that influence the antinociceptive activity of thymoquinone and their structural analogues.
Methods: The quinones were prepared by an oxidation procedure using molecular oxygen and catalysis with [CoII(salen)] from the respective phenols. The antinociceptive activity of para-benzoquinones (10 mg/kg, ip) was evaluated using formalin test in mice. Vehicle (5 % Tween 80) or morphine (10 mg/kg) were used as control group and standard drug, respectively. The amount of time spent licking the injected paw was considered as the nociceptive response.
Results: Among the compounds tested, five para-benzoquinones showed antinociceptive activity. The 2-isopropyl-para-benzoquinone presented the highest potency in first and second phases and produced a near-maximal inhibition (p < 0.001) in the formalin test, similar to morphine (p < 0.001).
Conclusion: Our experimental results show that by appropriate structural modification of parabenzoquinones it may be possible to develop novel analgesic drugs.
Keywords: Quinones, Antinociceptive activity, Analgesic, Central nervous system, Structure-activity relationship, Medicinal plant.
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Publicação 34
‘Anticonvulsant activity of thymoquinone and its structural analogues’
De Sousa, D. P.; Nóbrega, F. F. F.; Santos, C. C. M. P.; Benedito, R. B.; Vieira, Y. W.; Uliana, M. P.; Brocksom, T. J.; de Almeida, R. N.
Rev. Bras. Farmacognosia 2011, 21, 427-431.
DOI: 10.1590/S0102-695X2011005000040
Abstract:
It has been widely reported that the crude oil of Nigella sativa L., Ranunculaceae, seeds and its major chemical component thymoquinone present anticonvulsant activity. These facts led us to verify the pharmacological potential of five structurally related para-benzoquinones on the pentylenotetrazol-induced seizures model, and establish the structural characteristics that influence the anticonvulsant activity of thymoquinone. The unsubstituted para-benzoquinone was the compound that exhibited the highest potency, while 2-methyl-p-benzoquinone was inactive. It was found that the presence of alkyl groups attached to the ring influence the pharmacological activity of the para-benzoquinones. In addition, the number, position, and size of these groups change the anticonvulsant potency of the compounds.
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Publicação 33
(4R,4aS,4bS,7R,10aR)-4-Hydroxy-4a,7-dimethyl-2-(propan-2-yl)-1,4,4a,4b,5,6,7,8,10,10a-decahydrophenanthren-1-one
Caracelli, I.; Zukerman-Schpector, J.; Machado, A. T. L.; Brocksom, T. J.; Ferreira M. L.; Tiekink, E. R. T.
Acta Cryst. 2011, E67, o3136.
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Publicação 32
(4aS,4bR,7R,10aS)-3,7-Dimethyl-10a-(propan-2-yl)-1,4,4a,4b,5,6,7,8,10,10a-decahydrophenanthrene-1,4-dione
Caracelli, I.; Zukerman-Schpector, J.; Machado, A. T. L.; Brocksom, T. J.; Ferreira M. L.; Tiekink, E. R. T.
Acta Cryst. 2011, E67, o3192.
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Publicação 31
(4R *,4aS *,4bS *,5R *,10aR *)-4-Hydroxy-4a,5-dimethyl-2-(propan-2-yl)-1,4,4a,4b,5,6,7,8,10,10a-decahydrophenanthren-1-one
Caracelli, I.; Zukerman-Schpector, J.; Machado, A. T. L.; Brocksom, T. J.; Ferreira M. L.; Tiekink, E. R. T. Acta Cryst. 2011, E67, o3338.
DOI:
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