Six-membered ring systems: with O and/or S atoms

The most interesting chemistry published in 2020 on the synthesis of O- and S-six-membered heterocycles is reviewed. This personal overview is focused on the developments made on the synthesis of a large variety of natural compounds, specific reactions, and reagents for the preparation of natural and synthetic pyrans, chromenes and chromans, isochromenes and isochromans, pyranones, coumarins and isocoumarins, chromones and chromanones, xanthenes and xanthones, thiopyrans and analogues, dioxanes, dithiins, and also oxathianes.info:eu-repo/semantics/publishedVersio

Síntese e avaliação da actividade antioxidante de 2-estirilcromonas

Na primeira parte desta dissertação reporta-se a síntese de novos derivados de hidroxi-2-estirilcromonas. A síntese destes compostos foi feita recorrendo ao método de Baker-VenKataraman, partindo de 2’ - hidroxiacetofenonas e derivados de ácidos cinâmicos, ambos adequadamente substituídos. Na caracterização estrutural dos compostos sintetizados recorreu-se a técnicas analíticas actuais, em especial através de estudos de espectroscopia de ressonância magnética nuclear (RMN) [espectros de 1H, de 13C e de INEPT selectivo, estudos bidimensionais de correlação espectroscópica homo e heteronuclear e de efeito nuclear de Overhauser (NOE)]. Na segunda parte desta dissertação aborda-se a actividade antioxidante de compostos fenólicos e os métodos para avaliar essa actividade antioxidante. Estudou-se a acção das hidroxi-2- estirilcromonas sintetizadas na primeira parte na redução do radical DPPH*. Verificou-se que a presença de grupos orto-di-hidroxilo no anel B destes compostos é essencial para a actividade antirradicalar apresentada por eles. In the first part of this dissertation is reported the synthesis of some new hydroxy-2-styrylchromones. The synthesis of these compounds were carried out by a Baker-Venkataraman transformation, starting from 2’- hydroxyacetophenones and cinnamic acid derivatives. All synthesised compounds were characterised using modern analytical techniques, especially through nuclear magnetic resonance (NMR) spectroscopic studies. The NMR studies include 1H, 13C, selective INEPT, two dimensional homo and heteronuclear correlated spectroscopy and nuclear Overhauser effect (NOE) experiments. The second part of this dissertation deal with the antioxidant activity of phenolic compounds. We report the influence of hydroxy-2- styrylchromones, synthesised in the first part, in the reduction of DPPH radical. The presence of ortho-di-hydroxyl groups in the B ring of these compounds are essential for the antiradical activity presented by them

Transformações de cetonas α,β- e α,β,γ,δ-insaturadas. Novas rotas de síntese de 2,3-diarilxantonas

Esta dissertação é constituída por duas partes: na primeira parte reportam-se estudos de epoxidação em cetonas α,β- e α,β,γ,δ-insaturadas, catalisados por um complexo de salen Mn(III), conhecido como catalisador de Jacobsen; na segunda parte desenvolvem-se novas rotas de síntese de 2,3-diarilxantonas em que se recorre à reacção de Heck de cromonas bromadas com estirenos. Os estudos de epoxidação apresentados na primeira parte desta dissertação foram efectuados em três sistemas carbonílicos α,β- e α,β,γ,δ-insaturados: (E)-calconas, (E,E)-cinamilidenoacetofenonas e (E)-2-estirilcromonas e utilizando o peróxido de hidrogénio e o iodosilbenzeno como oxidantes. As reacções de epoxidação de (E)-calconas originaram os respectivos trans-epóxidos em bons rendimentos enquanto que nas (E)-2’-hidroxicalconas isolaram-se os produtos de ciclização dos respectivos trans-epóxidos, as trans-3-hidroxiflavanonas em rendimentos moderados. As reacções de epoxidação de (E,E)-cinamilidenoacetofenonas proporcionaram a formação dos respectivos γ,δ-trans-monoepóxidos e α,β:γ,δ- trans,trans-diepóxidos. De referir que no caso da (E)-4-nitrocinamilidenoacetofenona foi também possível isolar o α,β-trans-monoepóxido. Para as (E,E)-2’-hidroxicinamilidenoacetofenonas, além dos γ,δ-trans-monoepóxidos, isolaram-se os produtos resultantes da ciclização de α,β-trans-monoepóxidos, as (E)-2,3-trans-3-hidroxi-2-estiril-4-cromanonas. A epoxidação de (E,E)-γ-metilcinamilidenoacetofenonas originou uma mistura diasteriomérica dos γ,δ-trans-monoepóxidos, o que leva a considerar um mecanismo radicalar para este tipo de reacção. As reacções de epoxidação de (E)-2-estirilcromonas e (E)-5-hidroxi-2-estirilcromonas originaram os respectivas α,β-epóxidos, tendo sido necessário recorrer à técnica de HPLC para isolar os resultantes da epoxidação de (E)-5-hidroxi-2-estirilcromonas. Estudos de RMN e HPLC revelaram que apesar de ter sido utilizado um catalisador quiral na reacção de epoxidação, este não conseguiu induzir quiralidade em quaisquer dos produtos obtidos dos três tipos de compostos estudados. Na segunda parte desta dissertação aborda-se a síntese de novos derivados de xantona, nomeadamente 2,3-diarilxantonas. Para o efeito foram desenvolvidas duas rotas sintéticas. A primeira via de síntese utiliza como reagente de partida a 3-bromo-2-metilcromona e a segunda envolve a utilização de (E)-3-bromo-2-estirilcromonas.preparação de 3-bromo-2-metilcromonas envolveu; i) acetilação de 2’-hidroxiacetofenonas seguida de transposição do grupo acetilo; ii) bromação dos compostos cetónicos formados e ciclização do produto obtido, num passo único, originando as 3-bromo-2-metilcromonas. O derivado não substituído foi obtido em bom rendimento, os derivados 4’-benziloxilo e 6’-benziloxilo foram obtidos em rendimentos moderados, nao tendo sido possível isolar a 4’,6’-dibenziloxi-3-bromo-2-metilcromona. A preparação de (E)-3-bromo-2-estirilcromonas foi efectuada recorrendo ao método de Baker-Venkataraman, partindo de 2’-hidroxiacetofenonas e derivados de ácidos cinâmicos, ambos adequadamente substituídos. Os ésteres assim obtidos foram tratados com base originando as 3-hidroxi-1,4-pentadieno-4-onas que foram sujeitas, num só passo, a condições de bromação e ciclização do produto obtido, de forma a originar as pretendidas (E)-3-bromo-2-estirilcromonas. A síntese de 2,3-diarilxantonas partindo da 3-bromo-2-metilcromona envolveu reacções de Heck com estirenos comerciais e catalisadas por reagentes de paládio, obtendo-se (E)-2-metil-3-estirilcromonas. Por condensação aldólica destas com benzaldeídos originaram (E,E)-2,3-diestirilcromonas, que após refluxo em 1,2,4-triclorobenzeno dão origem às pretendidas 2,3-diarilxantonas. A reacção de Heck de (E)-3-bromo-2-estirilcromonas e estirenos levou à formação directa de 2,3-diarilxantonas. Esta transformação explica-se pela formação de (E,E)-2,3-diestirilcromonas, seguida de processos de electrociclização e oxidação. Foi também possível isolar neste tipo de reacção 2,3-diaril-3,4-di-hidroxantonas, intermediários semi-oxidados das xantonas obtidas. A última etapa deste trabalho consistiu na desalquilação das benziloxi- e metoxi-2,3-diarilxantonas sintetizadas. Na caracterização estrutural dos compostos sintetizados recorreu-se a técnicas analíticas actuais, em especial através de estudos de espectroscopia de ressonância magnética nuclear (RMN) [espectros de 1H, de 13C e estudos bidimensionais de correlação espectroscópica homo e heteronuclear e de efeito nuclear de Overhauser (NOESY)]. Estes estudos foram também essenciais no estabelecimento da estereoquímica presente na maioria dos compostos sintetizados. Os novos produtos obtidos foram igualmente caracterizados por espectrometria de massa recorrendo em alguns casos à técnica de impacto electrónico noutros, à técnica de “electrospray” e sempre que possível acompanhados de microanálise elementar ou espectrometria de massa de alta resolução.This dissertation is constituted by two parts: in the first one we report the epoxidation studies of α,β-and α,β,γ,δ-unsaturated ketones, catalysed by the well-known Jacobsen catalyst; in the second one novel routes of 2,3-diarylxanthones were developed, in which we use the Heck reaction of bromochromones with styrenes. The epoxidation studies presented in the firs part of this dissertation were accomplished in three α,β-unsaturated carbonylic systems: (E)-chalcones, (E,E)-cinnamylideneacetophenones and (E)-2-styrylchromones using hydrogen peroxide and iodosylbenzene as oxidants. Good yields were obtained in the synthesis of chalcone trans-epoxides; concerning the (E)-2’-hydroxychalcones, the cyclisation products of the epoxides, trans-3-hydroxyflavanones, were obtained in moderated yields. The epoxidation of (E,E)-cinnamylideneacetophenones leads to the formation of the respective γ,δ-trans-monoepoxides and α,β:γ,δ-trans,trans-diepoxides. In the case of the (E)-4-nitrocinnamylideneacetophenone it was also possible to isolate the α,β-trans-monoepoxide. For (E,E)-2’-hydroxycinnamylideneacetophenones besides the γ,δ-trans-monoepoxides it was also possible to isolate the cyclisation products of the α,β-trans-monoepoxides, (E)-2,3-trans-3-hydroxy-2-styryl-4-chromanones. The epoxidation of (E,E)-γ-methylcinnamylideneacetophenones gives a diasteriomeric mixture of γ,δ-trans-monoepoxides which lead us to propose a stepwise radicalar mechanism. The epoxidation of (E)-2-styrylchromones and (E)-5-hydroxystyrylchromones leads to the formation of the respective α,β-trans-epoxides, being necessary the use of HPLC to separate those obtained from (E)-5-hydroxystyrylchromones. NMR and HPLC studies showned that no chirality were induced in the epoxidation products of any of the studies, in spite of the use of chiral catalyst. The second part of this dissertation is dedicated to the synthesis of novel xantone derivatives, mainly 2,3-diarylxanthones. To achive the target, two synthetic routes were developed: The first uses the 3-bromo-2-methylchromone as starting material and the second one uses (E)-3-bromo-2-styrylchromones.This dissertation is constituted by two parts: in the first one we report the epoxidation studies of α,β-and α,β,γ,δ-unsaturated ketones, catalysed by the well-known Jacobsen catalyst; in the second one novel routes of 2,3-diarylxanthones were developed, in which we use the Heck reaction of bromochromones with styrenes. The epoxidation studies presented in the firs part of this dissertation were accomplished in three α,β-unsaturated carbonylic systems: (E)-chalcones, (E,E)-cinnamylideneacetophenones and (E)-2-styrylchromones using hydrogen peroxide and iodosylbenzene as oxidants. Good yields were obtained in the synthesis of chalcone trans-epoxides; concerning the (E)-2’-hydroxychalcones, the cyclisation products of the epoxides, trans-3-hydroxyflavanones, were obtained in moderated yields. The epoxidation of (E,E)-cinnamylideneacetophenones leads to the formation of the respective γ,δ-trans-monoepoxides and α,β:γ,δ-trans,trans-diepoxides. In the case of the (E)-4-nitrocinnamylideneacetophenone it was also possible to isolate the α,β-trans-monoepoxide. For (E,E)-2’-hydroxycinnamylideneacetophenones besides the γ,δ-trans-monoepoxides it was also possible to isolate the cyclisation products of the α,β-trans-monoepoxides, (E)-2,3-trans-3-hydroxy-2-styryl-4-chromanones. The epoxidation of (E,E)-γ-methylcinnamylideneacetophenones gives a diasteriomeric mixture of γ,δ-trans-monoepoxides which lead us to propose a stepwise radicalar mechanism. The epoxidation of (E)-2-styrylchromones and (E)-5-hydroxystyrylchromones leads to the formation of the respective α,β-trans-epoxides, being necessary the use of HPLC to separate those obtained from (E)-5-hydroxystyrylchromones. NMR and HPLC studies showned that no chirality were induced in the epoxidation products of any of the studies, in spite of the use of chiral catalyst. The second part of this dissertation is dedicated to the synthesis of novel xantone derivatives, mainly 2,3-diarylxanthones. To achive the target, two synthetic routes were developed: The first uses the 3-bromo-2-methylchromone as starting material and the second one uses (E)-3-bromo-2-styrylchromones.The preparation of 3-bromo-2-methylchromones was made through: i) acetylation of 2’-hydroxyacetophenones followed by the transposition of the acetyl group, ii) bromination of the formed ketonic compounds and cyclisation in one step, giving the desired 3-bromo-2-methylchromones. The unsubstituted derivative was obtained in good yield, the 4’-benzyloxy and 6’-benzyloxy derivatives were obtained in moderate yields and it was not possible to isolate 4’,6’-dibenzyloxy-3-bromo-2-methylchromone. (E)-3-Bromo-2-styrylchromones were obtained by the Baker-Venkataraman method, starting with 2’-hydroxyacetophenones and cinnamic acid derivatives, both appropriated substituted. The formed esters were treated with base giving 3-hydroxy-1,4-pentadiene-1-ones which were submitted to bromination and cyclisation in one step in order to achive the desired (E)-3-bromo-2-styrylchromones. The synthesis of 2,3-diarylxanthones starting from the 3-bromo-2-methylchromones involved a Heck reaction with commercial styrenes, catalysed by palladium catalysts, to afford (E)-2-methyl-3-styrylchromones. The aldol condensation of these products with benzaldehydes leads to (E,E)-2,3-distyrylchromones, which after reflux in 1,2,4-trichlorobenzene gives the desired 2,3-diarylxanthones. A Heck reaction between (E)-3-bromo-2-styrylchromones and commercial styrenes aforded directly the desired 2,3-diarylxanthones. This transformation is explained by the formation of (E,E)-2,3-distyrylchromones followed by electrocyclisation and oxidation processes. It was also possible to isolate in this type of reaction 2,3-diaryl-3,4-di-hidroxanthones, semi-oxidized intermediates of the obtained xanthones. Finally the dealkylation of the benzyloxy- and methoxy-2,3-diarylxanthones synthetized were performed in order to prepare hydroxy-2,3-diarylxanthones. All the synthesised compounds were characterised using modern analytical techniques, with special emphasis on exhaustive nuclear magnetic resonance (NMR) spectroscopic studies [1H and 13C spectra, two dimensional homonuclear and heteronuclear spectroscopy and NOESY]. All the new compounds were also characterized by mass spectrometry, in some cases using electronic impact and in others electrospray ionization technique and as long as possible elemental analysis or high resolution mass spectrometry were also carried on

Synthesis of new hydroxy-2-styrylchromones

http://apps.isiknowledge.com/full_record.do?product=UA&search_mode=GeneralSearch&qid=5&SID=V1M67gPH3IpI7j5a98j&page=1&doc=1&colname=WOSHydroxy-2-styrylchromones 5a−i were prepared by debenzylation of benzyloxy-2-styrylchromones 3a−i, which were synthesised by the Baker−Venkataraman method. The last step of this method, the cyclodehydration 5-aryl-3-hydroxy- 1-(2-hydroxyaryl)-2,4-pentadien-1-ones 2a−i, was carried out with a catalytic amount of iodine, or p-toluenesulfonic acid, in DMSO. Benzyloxy-3-cinnamoyl-2-styrylchromones 4a−f were obtained as by-products in both procedures, but the latter procedure gave benzyloxy-2- styrylchromones 3a−i in better yields. The structures of all new compounds were established by extensive NMR studies

Novel Hydroxy-9H-xanthen-9-ones derivatives: synthesis and bioactive properties

9H-Xanthen-9-ones commonly referred as xanthones are a large group of natural heterocyclic compounds with significant bioactive properties (e.g. anti-inflammatory, antibacterial, antimalarial, cytotoxicity and radical scavenging activity).1 In order to explore some of these biological assessments, we developed two methodologies for the synthesis of novel hydroxylated 2,3-diarylxanthone derivatives. The first synthetic route is based on the Heck reaction of the 3-bromochromone 2 followed by aldol condensation and electrocyclisation/oxidation processes to afford the 2,3-diaryl-9H-xanthen-9-ones 1. An efficient and more general approach is the Heck reaction of 3-bromo-2-styrylchromones 3 with styrenes as olefins followed by the in situ electrocyclisation/oxidation processes.2 Pharmacological studies involving the hydroxy-9H-xanthen-9-ones 1,3 which are obtained after cleavage of the methyl group, will also be presented and discussed

Epoxidação de (E,E)-Cinamilidenoacetofenonas com Peróxido de Hidrogénio

As (E,E)-cinamilidenoacetofenonas pertencem a um importante grupo de cetonas a,β,Y,∂-insaturadas, cuja síntese envolve a condensação aldólica de acetofenonas com cinamaldeídos adequadamente substituídos. Certos derivados saturados, as 1,5-diaril-1-pentanonas, foram isolados a partir de plantas usadas na medicina tradicional da Africa tropical, da Ásia e da Austrália e demonstraram possuir forte actividade anti-bacteriana.2 No entanto, os compostos desta família com mais aplicações são as (E,E)-2'-hidroxicinamilidenoacetofenonas, as quais constituem uma importante classe de intermediários na síntese de 2- estirilcromonas.3 A epoxidação deste tipo de compostos com dimetildioxirano ou com o método de epoxidação assimétrica de Juliá já foi descrita, embora neste último caso se tenha utilizado um só derivado.4 Tendo em conta o nosso estudo da reactividade de (E,E)- cinamilidenoacetofenonas e a potencialidade dos epóxidos obtidos na síntese duma grande variedade de novos compostos, decidiu-se estudar o efeito da utilização do catalisador de salen Mn(III) na epoxidação da (E,E)-cinamilidenoacetofenona 1a usando o H2O2 como oxidante

NMR in the epoxidation of (E,E)-Cinnamylideneacetophenones

The epoxidation of cinnamylideneacetophenones have been already performed with hydrogen peroxide as an oxidant in Julia's method [1] and with dimethyldioxirane [2], however no studies were performed using salen Mn(III) complexes as catalysts.The epoxidation of cinnatnylideneacetophenones have been already performed with hydrogen peroxide as oxidant in Julia's method [1] and with dimethyldioxirane [2], however no studies were performed using salen Mn(lll) complexes as catalysts. On these basis, we developed a study on the epoxidation of cinnamylideneacetophenones 1, catalyzed by coinmercially available Jacobsen's catalyst [salen Mn(IIl)] and using iodosy I benzene and hydrogen peroxide as oxidants. The structure of the epoxidation products 2-5, their stereochemistry and the regiochemistry of the monoepoxides 2 fotmation were established by ID and 2D NMR spectroscopy. These studies will be presented and discussed

Cholesterol-based compounds: Recent advances in synthesis and applications

This review reports on the latest developments (since 2014) in the chemistry of cholesterol and its applications in different research fields. These applications range from drug delivery or bioimaging applications to cholesterol-based liquid crystals and gelators. A brief overview of the most recent synthetic procedures to obtain new cholesterol derivatives is also provided, as well as the latest anticancer, antimicrobial, and antioxidant new cholesterol-based derivatives. This review discusses not only the synthetic details of the preparation of new cholesterol derivatives or conjugates, but also gives a short summary concerning the specific application of such compoundsThanks are due to the University of Aveiro, Instituto Politécnico de Bragança, FCT/MEC for financial support of the QOPNA (FCT UID/QUI/00062/2013) and CIMO (UID/AGR/00690/2013) research units, through national funds, and where applicable cofinanced by the FEDER, within the PT2020 Partnership Agreement; and also to the Portuguese NMR Network. This work was also supported by the Integrated Programme of SR&TD “pAGE–Protein aggregation Across the Lifespan” (reference CENTRO-01-0145-FEDER-000003), co-funded by the Centro 2020 program, Portugal 2020, European Union, through the European Regional Development Fund. H. M. T. Albuquerque thanks the pAGE project for his Post-Doc grant (BPD/UI98/4861/2017).info:eu-repo/semantics/publishedVersio

A comprehensive review on xanthone derivatives as α-glucosidase inhibitors

α-Glucosidase plays an important role in carbohydrate metabolism and is therefore an attractive therapeutic target for the treatment of diabetes, obesity and other related complications. In the last two decades, considerable interest has been given to natural and synthetic xanthone derivatives in this field of research. Herein, a comprehensive review of the literature on xanthones as inhibitors of α-glucosidase activity, their mechanism of action, experimental procedures and structure-activity relationships have been reviewed for more than 280 analogs. With this overview we intend to motivate and challenge researchers (e.g. chemistry, biology, pharmaceutical and medicinal areas) for the design of novel xanthones as multipotent drugs and exploit the properties of this class of compounds in the management of diabetic complications.This work received financial support from the European Union (FEDER funds POCI/01/0145/FEDER/007265) and National Funds (FCT/MEC, Fundação para a Ciência e Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreement PT2020 UID/QUI/50006/2013; FCT UID/QUI/00062/2013, and “Programa Operacional Competitividade e Internacionalização” (COMPETE) (POCI- 01-0145-FEDER-029241), and under the framework of QREN (NORTE-01-0145-FEDER-000024). Thanks are also due to Faculdade de Farmácia da Universidade do Porto and Instituto Politécnico de Bragança.info:eu-repo/semantics/publishedVersio

Synthesis and transformation of halochromones

Chromones (4H-1-benzopyran-4-ones) are one of the most abundant groups of naturally occurring oxygen containing heterocyclic compounds possessing a benzo-γ-pyrone framework, 1a. The significance of these widely spread and highly diverse compounds is far beyond the important biological functions they assume in nature [1, 2]. Natural and synthetic chromone derivatives have been assigned as lead structures in drug development with some already being marketed [3]. The majority of the naturally occurring chromones are 2- and 3-aryl derivatives, called flavones 1b and isoflavones 1c, respectively. However, other types of chromones have also been found in the plant kingdom, such as 3-methylchromones 1d and 2- styrylchromones 1e (Fig. 1).University of Aveiro, Fundação para a Ciência e a Tecnologia (FCT, Portugal), European Union, QREN, FEDER and COMPETE for funding the QOPNA Research Unit