Synthesis and stereochemical assignment of methyl 3-(3-hydroxyphenoxy) acrylate via cis-trans photoisomerization

Methyl 3-(3-hydroxyphenoxy)acrylate (2), a new and important starting material for several reactions and a potential precursor of the natural product 3-(3-hydroxyphenoxy)-2-propenal (1), was synthesized from resorcinol and methyl propiolate. The trans configuration of the double bond present in 2 was confirmed through a photoisomerization reaction.3-(3-Hidroxi-fenoxi)acrilato de metila (2), um novo e importante material de partida para inúmeras reações e um precursor potencial do produto natural 3-(3-hidroxi-fenoxi)-2-propenal (1), foi sintetizado a partir de resorcinol e propiolato de metila. A configuração trans da dupla ligação presente no composto 2 foi confirmada através de uma reação de fotoisomerização.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Synthesis of Analogues of Thyroid Hormones: Nuclear Receptor Modulators

Thyroid hormones are essential for the development and differentiation of all cells of the human body. This work reports the synthesis of some synthetic structural analogues of thyroid hormones, which may be modulators of the thyroid hormone receptor. The known compounds GC-1 (Sobetirome) and CG-24 were successfully prepared and two novel analogous molecules were also synthesized by a new and efficient synthetic methodology. DOI: http://dx.doi.org/10.17807/orbital.v7i3.73

Monoketonic Curcuminoid Lidocaine Co Deliver Using Thermosensitive Organogels From Drug Synthesis to Epidermis Structural Studies

Organogels ORGs are remarkable matrices due to their versatile chemical composition and straightforward preparation. This study proposes the development of ORGs as dual drug carrier systems, considering the application of synthetic monoketonic curcuminoid m CUR and lidocaine LDC to treat topical inflammatory lesions. The monoketone curcuminoid m CUR was synthesized by using an innovative method via a NbCl5 acid catalysis. ORGs were prepared by associating an aqueous phase composed of Pluronic F127 and LDC hydrochloride with an organic phase comprising isopropyl myristate IPM , soy lecithin LEC , and the synthesized m CUR. Physicochemical characterization was performed to evaluate the influence of the organic phase on the ORGs supramolecular organization, permeation profiles, cytotoxicity, and epidermis structural characteristics. The physico chemical properties of the ORGs were shown to be strongly dependent on the oil phase constitution. Results revealed that the incorporation of LEC and m CUR shifted the sol gel transition temperature, and that the addition of LDC enhanced the rheological G amp; 8242; G amp; 8243; ratio to higher values compared to original ORGs. Consequently, highly structured gels lead to gradual and controlled LDC permeation profiles from the ORG formulations. Porcine ear skin epidermis was treated with ORGs and evaluated by infrared spectroscopy FTIR , where the stratum corneum lipids were shown to transition from a hexagonal to a liquid crystal phase. Quantitative optical coherence tomography OCT analysis revealed that LEC and m CUR additives modify skin structuring. Data from this study pointed ORGs as promising formulations for skin deliver

Synthesis of Analogues of Thyroid Hormones: Nuclear Receptor Modulators

Thyroid hormones are essential for the development and differentiation of all cells of the human body. This work reports the synthesis of some synthetic structural analogues of thyroid hormones, which may be modulators of the thyroid hormone receptor. The known compounds GC-1 (Sobetirome) and CG-24 were successfully prepared and two novel analogous molecules were also synthesized by a new and efficient synthetic methodology. DOI: http://dx.doi.org/10.17807/orbital.v7i3.73

Study about the synthesis of autoregulators butyrolactones of the Streptomyces bacteria.

Streptomycetes são bactérias filamentosas Gram-positivas bastante conhecidas pela capacidade de produzir uma grande variedade de metabólitos secundários e substâncias biologicamente ativas. Essas atividades são controladas por alguns compostos de baixo peso molecular, denominados butirolactonas autoreguladoras. A maioria desses compostos com propriedades autoreguladoras possuem como característica estrutural comum a presença de um esqueleto g-butirolactônico 2,3-dissubstituído, mas mostram pequenas diferenças estruturais na cadeia lateral. Essas moléculas, cujas estruturas são mostradas abaixo, são classificadas nos tipos: virginiae butanolidas (VB) A-E, fatores de Gräfe, butanolida IM-2, o fator-I e o fator-A. Neste trabalho foram desenvolvidos estudos visando testar um novo caminho sintético para a obtenção de análogos do fator-A e, através da redução enantiosseletiva da carbonila da cadeia lateral dos compostos obtidos, seria possível sintetizar também as outras butirolactonas autoreguladoras. Inicialmente, o intermediário necessário para a síntese dos compostos desejados foi preparado através de uma reação de transesterificação, a qual foi amplamente estudada. Em seguida, uma reação de ciclização intramolecular deste intermediário daria origem aos análogos do fator-A de interesse. Entretanto, após várias tentativas empregando diferentes condições reacionais, não foi possível obter tais compostos. Com intuito de explicar e confirmar os resultados experimentais obtidos realizou-se cálculos teóricos que possibilitaram concluir este estudo de maneira apropriada. Outras duas abordagens sintéticas para a preparação de análogos do fator-A foram também desenvolvidas e testadas. No entanto, apresentaram dificuldades no decorrer da execução e, consequentemente, não forneceram resultados promissores. Então, um novo estudo de reações químicas, baseado em um método de síntese de butirolactonas através de uma reação intermolecular, foi desenvolvido. Esta nova estratégia sintética possibilitaria a obtenção de análogos do fator-A em apenas 3 etapas, constituindo-se de uma reação de abertura de um anel oxirano, seguida de uma reação de ozonólise e de uma redução seletiva de um grupo aldeído. Os diferentes substituintes presentes nos epóxidos testados apresentaram efeitos bastante distintos, os quais foram mais bem entendidos com o auxílio de cálculos teóricos. A obtenção, com 52% de rendimento, da butirolactona desejada, um produto intermediário contendo uma olefina terminal em uma das cadeias laterais, demonstra o sucesso desta nova estratégia sintética. Entretanto, com os reagentes utilizados até o momento, a reação de ozonólise que forneceria o aldeído desejado não apresentou resultados satisfatórios. Provavelmente, a dificuldade encontrada nesta etapa está relacionada com a volatilidade, a solubilidade em água e/ou a degradação do aldeído formado, tornando difícil o seu isolamento. No entanto, como esse tipo de reação já foi descrito com sucesso na literatura empregando-se K2OsO4, N-óxido de N-metilmorfolina (NMO) e NaIO4 como reagentes da reação de clivagem da dupla ligação olefínica, temos a convicção de que o nosso objetivo será alcançado em breve com as modificações das condições reacionais e/ou dos reagentes necessários para efetuar com sucesso essa última etapa.Streptomycetes are Gram-positive filamentous bacteria well known for the ability to produce a wide variety of secondary metabolites and biologically active substances. These activities are controlled by low-molecular-weight compounds called butyrolactone autoregulators. The greater number of these compounds with autoregulators properties have as common characteristic a 2,3-disubstituted-g-butyrolactone sketeton, but show minor structural differences in the side chain. These molecules, whose structures are shown below, are classified following the types: virginiae butanolides (VB) A-E, Gräfe\'s factors, IM-2 butanolide, I-factor and A-factor. In this work, studies were developed with aim to test a new synthetic pathway to obtain A-factor analogous, which by enantioselective reduction of the carbonyl group of the side chain can be converted into others butyrolactone autoregulators. First of all, the necessary intermediary for the synthesis of the desired compounds was prepared by a transesterification reaction, which was widely studied. After that, an intramolecular cyclization reaction of this intermediary could to produce the A-factor analogous. However, after several attempts employing different reactional conditions, the desired compounds were not obtained. Theoretical calculation was realized as an attempt to explain the experimental results obtained and should possible to conclude this study adequately. Two other two synthetic approaches for the preparation A-factor analogous were developed and tested, but the results were not good enough. Thus, a new study based on a method of intermolecular synthesis of butyrolactones was developed. This new synthetic strategy would allow to obtain the A-factor in only 3 steps: a reaction of oxirane ring opening, followed by an ozonolysis reaction and a selective reduction of an aldehyde group. The different groups present in the epoxides tested showed different effects, which were better understood with the aid of theoretical calculation. The attainment of the desired butyrolactone with 52% yield, a product containing a terminal olefin, confirm the success of this new synthetic strategy. However, up to this moment, the ozonolysis reaction was not giving good results. The difficulty for this step is probably associated with the volatileness, the high solubility in water and/or the degradation of the aldehyde formed, making difficult its isolation. However, as this type of reaction is already reported in the literature employing the reagents K2OsO4, N-methylmorpholine N-oxide (NMO) and NaIO4 to cleave the terminal double, we have the conviction that our aim could be accomplished with modifications on the reactional conditions and/or of the reagents which are necessary to realize with success this final step

Influência do gás de proteção na soldagem com arames de aços inoxidáveis ferríticos

Para obter uma boa soldabilidade dos aços inoxidáveis ferríticos, na maioria das vezes, as empresas recorrem ao arames inoxidáveis austenítico em função de sua boa resistência mecânica, tenacidade e ductilidade. Arames de aço inoxidável ferrítico estabilizados ao nióbio e titânio estão sendo desenvolvidos para obter boa qualidade e baixo custo. O objetivo deste trabalho é estudar a influência da composição do gás de proteção (argônio puro e misturas com oxigênio ou dióxido de carbono) na composição química e microestrutura do cordão de solda do processo GMAW com transferência por curto-circuito. Foram utilizados dois arames eletrodos estabilizados (ER430Ti e ER430LNb) e um arame eletrodo não estabilizado (ER430) e como metal de base o aço inoxidável ferrítico UNS 43932. Os resultados mostraram que o aumento do dióxido de carbono no gás de proteção aumenta o teor de carbono no cordão de solda, tendo como conseqüência para o arame não estabilizado um aumento significativo da quantidade de martensita no cordão de solda, caso não observado de forma significativa com o aumento do oxigênio. Para o arame ER430LNb não verificou a presença da martensita de contorno de grão. O aumento tanto do dióxido de carbono como do oxigênio diminuiu os teores de Mn e Si para os arames ER430LNb e ER430, caso não verificado no arame ER430Ti.For a good ferritics stainless steel weldability, most of the time, the companies use the austenitic stainless wires because they have good mechanical resistance, tenacity and ductility. Ferritics stainless steel wires stabilized with niobium and titanium are being developed to obtain good quality and low costs. The aim of this work is to study the influence of shielding gas composition (pure argon and mixtures with oxygen or carbon dioxide) on the chemical composition and microstructures of weld fillet with the GMAW process with short-circuit transfer. It was used two stabilized electrode wires (ER430Ti and ER430LNb) and a non-stabilized electrode wire (ER430) and ferritic stainless steel UNS 43932 was used as base metal. The results showed that the increase of carbon dioxide in the shielding gas increases the carbon content in the weld fillet and in the non stabilized wire increases significantly the quantity of martensite in the weld fillet, which was not observed with the increase of oxygen. To ER430LNb wire it was not observed martensite in the grain boundary. It was observed that increasing either carbon dioxide or oxygen generates a decline of Mn e Si to ER430LNb and ER430 wires, case not observed in ER430Ti wire

Monoketonic Curcuminoid-Lidocaine Co-Deliver Using Thermosensitive Organogels: From Drug Synthesis to Epidermis Structural Studies

Organogels (ORGs) are remarkable matrices due to their versatile chemical composition and straightforward preparation. This study proposes the development of ORGs as dual drug-carrier systems, considering the application of synthetic monoketonic curcuminoid (m-CUR) and lidocaine (LDC) to treat topical inflammatory lesions. The monoketone curcuminoid (m-CUR) was synthesized by using an innovative method via a NbCl5–acid catalysis. ORGs were prepared by associating an aqueous phase composed of Pluronic F127 and LDC hydrochloride with an organic phase comprising isopropyl myristate (IPM), soy lecithin (LEC), and the synthesized m-CUR. Physicochemical characterization was performed to evaluate the influence of the organic phase on the ORGs supramolecular organization, permeation profiles, cytotoxicity, and epidermis structural characteristics. The physico-chemical properties of the ORGs were shown to be strongly dependent on the oil phase constitution. Results revealed that the incorporation of LEC and m-CUR shifted the sol-gel transition temperature, and that the addition of LDC enhanced the rheological G′/G″ ratio to higher values compared to original ORGs. Consequently, highly structured gels lead to gradual and controlled LDC permeation profiles from the ORG formulations. Porcine ear skin epidermis was treated with ORGs and evaluated by infrared spectroscopy (FTIR), where the stratum corneum lipids were shown to transition from a hexagonal to a liquid crystal phase. Quantitative optical coherence tomography (OCT) analysis revealed that LEC and m-CUR additives modify skin structuring. Data from this study pointed ORGs as promising formulations for skin-delivery