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Abstract(s)
A oxidação alílica é um processo sintético de grande importância industrial devido à sua ampla variedade de aplicações na síntese de produtos químicos e farmacêuticos. Alguns exemplos relevantes deste tipo de reação incluem a oxidação de ?5-esteroides aos seus derivados ?5-7-oxoesteroides correspondentes. Os métodos clássicos para realização destas reações envolvem o uso de um excesso de reagentes indesejáveis de crómio, manganésio ou selénio. Recentemente o uso de hidroperóxidos, em combinação com diferentes tipos de catalisadores metálicos em formas homogéneas e heterogéneas, tem despertado interesse. Posteriormente, outros processos diferentes foram relatados e, entre estes, a combinação de clorito de sódio, como oxidante, e N-hidroxiftalimida, como catalisador, revelou ser um procedimento eficiente e mais aceitável em termos ambientais para esta transformação. Para acelerar esta reação de oxidação, o potencial de vários catalisadores metálicos foi explorado. Na presente dissertação descrevem-se oxidações alílicas de ?5-esteroides nestas condições, mas explorando o uso de compostos de vanádio, como o VO(acac)2, bem como de outros catalisadores metálicos. Curiosamente, o consumo total de substrato foi observado após 15 minutos de reação; no entanto, um produto secundário também foi detetado, além dos ?5-7-oxoesteroides esperadas. Na tentativa de ultrapassar esta observação, diferentes condições de oxidação foram também investigadas com o objetivo de melhorar este processo oxidativo.
Para além disso, foi também estudado o efeito antiproliferativo de alguns ?5-esteroides e os seus correspondentes ?5-7-oxoesteroides, em linhas celulares PC3 e N27. Este estudo foi realizado com o intuito de avaliar o potencial destes compostos como agentes anticancerígenos, tendo sido calculado o IC50 de cada um destes compostos. Interessantemente, verificou-se que os compostos 7-oxidados da diosgenina e da pregnenolona se apresentaram mais tóxicos que os percursores não oxidados para a linha celular PC3.
Allylic oxidations are industrially important synthetic processes due to their wide variety of applications in the synthesis of pharmaceuticals and fine chemicals. Relevant examples include the oxidation of ?5-steroids to the corresponding ?5-7-ketone derivatives. Classical methods to perform these reactions involve the use of large excess of undesirable chromium, manganese or selenium reagents. Of particular interest is the use of hydroperoxides, combined with different types of metal catalysts in homogeneous and heterogeneous forms. Later, other different processes were reported and, among these, the combination of sodium chlorite as the oxidant and N-hydroxyphthalimide as catalyst revealed to be a green procedure for this transformation. In order to accelerate this oxidation reaction, the potential interest of several metal catalysts was explored. Here is reported the very fast allylic oxidations of ?5-steroids by using vanadium compounds such as VO(acac)2 as well as other metal catalysts. Interestingly, total substrate consumption was observed after 15 minutes of reaction; however, a side product was also detected in addition to the expected ?5-7-ketones. Therefore, different oxidation conditions were also explored to improve this oxidation process. Moreover, it was also studied the antiproliferative effects of some ?5-steroids and their corresponding ?5-7-ketones on PC3 and N27 cell lines to understand the potential of these compounds as anticancer agents and the corresponding IC50 was also calculated. Interestingly, it was observed that 7-oxodiosgenin and 7-oxopregnenolone have higher cytotoxicity against PC3 cells than the observed with the corresponding precursors.
Allylic oxidations are industrially important synthetic processes due to their wide variety of applications in the synthesis of pharmaceuticals and fine chemicals. Relevant examples include the oxidation of ?5-steroids to the corresponding ?5-7-ketone derivatives. Classical methods to perform these reactions involve the use of large excess of undesirable chromium, manganese or selenium reagents. Of particular interest is the use of hydroperoxides, combined with different types of metal catalysts in homogeneous and heterogeneous forms. Later, other different processes were reported and, among these, the combination of sodium chlorite as the oxidant and N-hydroxyphthalimide as catalyst revealed to be a green procedure for this transformation. In order to accelerate this oxidation reaction, the potential interest of several metal catalysts was explored. Here is reported the very fast allylic oxidations of ?5-steroids by using vanadium compounds such as VO(acac)2 as well as other metal catalysts. Interestingly, total substrate consumption was observed after 15 minutes of reaction; however, a side product was also detected in addition to the expected ?5-7-ketones. Therefore, different oxidation conditions were also explored to improve this oxidation process. Moreover, it was also studied the antiproliferative effects of some ?5-steroids and their corresponding ?5-7-ketones on PC3 and N27 cell lines to understand the potential of these compounds as anticancer agents and the corresponding IC50 was also calculated. Interestingly, it was observed that 7-oxodiosgenin and 7-oxopregnenolone have higher cytotoxicity against PC3 cells than the observed with the corresponding precursors.
Description
Keywords
Esteroides Oxodesidroepiandrosterona Oxoesteroides Citotoxicidade Desidroepiandrosterona Oxidação Alílica