{"id":111084,"date":"2018-03-11T10:37:27","date_gmt":"2018-03-11T10:37:27","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/sa%c2%adntesis-del-esqueleto-tetraca%c2%adclico-de-las-welwistatinas\/"},"modified":"2018-03-11T10:37:27","modified_gmt":"2018-03-11T10:37:27","slug":"sa%c2%adntesis-del-esqueleto-tetraca%c2%adclico-de-las-welwistatinas","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/quimica\/sa%c2%adntesis-del-esqueleto-tetraca%c2%adclico-de-las-welwistatinas\/","title":{"rendered":"S\u00edntesis del esqueleto tetrac\u00edclico de las welwistatinas"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Miriam Ruiz Serrano <\/strong><\/h2>\n<p>Las welwitindolinonas constituyen un grupo de alcaloides de gran inter\u00e9s qu\u00edmico y farmacol\u00f3gico, tanto por su estructura novedosa como por la actividad biol\u00f3gica que presentan. Concretamente la welwistatina, ha mostrado una potente actividad anti-md r que ha sido el motivo por el cual la hemos elegido como modelo para la s\u00edntesis del esqueleto tetrac\u00edclico de las welwistatinas.  las principales transformaci\u00f3n de inter\u00e9s sint\u00e9tico que se han puesto a punto en este trabajo de tesis doctoral y que nos han permitido sintetizar el n\u00facleo  tetrac\u00edclico  de las welwistatinas pueden resumirse en los siguientes puntos: 1-\tpreparaci\u00f3n de derivados de ?-Isopropilidenciclohexanonas cuyo tratamiento posterior con el indol o el n-metilindol por irradiaci \u00f3n ultras\u00f3nica en presencia de \u00e1cido p-toluenosulf\u00f3nico, proporciona los aductos de michael esperados sobre los que se ensayaron diversas condiciones de ciclaci\u00f3n, una de las cuales, nos proporciona un nuevo acceso a la s\u00edntesis de n-tosil-?-Cetoamid as c\u00edclicas, cuando la reacci\u00f3n tiene lugar entre derivados de 2-formilciclohexanona y tosilhidrazina, seguida del tratamiento del crudo de reacci\u00f3n con trifluoroacetato de rodio.    2-\tse ha conseguido la formaci\u00f3n del anillo c del sistema ciclohexa [cd]indol de los derivados de welwistatina, por expansi\u00f3n e inserci\u00f3n regioselectiva de diazoacetato de etilo en presencia, de tetrafluoroborato de trietiloxonio, de la cenota de kornfeld.    3-\tel acceso al n\u00facleo tetrac\u00edclico de las welwistatina es  trav\u00e9s de una secuencia de reacciones domin\u00f3 ani\u00f3nicas que incluye una adici\u00f3n de  michael, adici\u00f3n ald\u00f3lica e hidr\u00f3lisis del grupo pivaloilo, lo cual constituye la s\u00edntesis m\u00e1s eficaz de las descritas hasta la fecha de este tipo de estructuras; ade m\u00e1s esta estrategia sint\u00e9tica deja un grupo hidroxilo en la posici\u00f3n 13 del anillo d que permitir\u00e1 su posterior funcionalizaci\u00f3n. As\u00ed mismo la reacci\u00f3n de los derivados tetrac\u00edclicos ind\u00f3licos con n-bromosuccinimida en alcohol terc-but\u00edlico, seguida de deshalogenaci\u00f3n reductora en condiciones radicalarias. Permite la obtenci\u00f3n diastereoselectiva de derivados de oxindol con la configuraci\u00f3n relativa de la 3-epiwelwistatina.    3- finalmente se ha desarrollado un nuevo m\u00e9todo de desprotecci\u00f3n de s istemas de n-pivaloilindol y n-pivaloilcarbazol por reacci\u00f3n de estos con dbu en tetrahidrofurano h\u00famedo.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>S\u00edntesis del esqueleto tetrac\u00edclico de las welwistatinas<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 S\u00edntesis del esqueleto tetrac\u00edclico de las welwistatinas <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Miriam Ruiz Serrano <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Complutense de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 27\/09\/2011<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>alvarado Gutierrez Lopez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Elena de la Cuesta el\u00f3segui <\/li>\n<li>david D\u00edez mart\u00edn (vocal)<\/li>\n<li>Juan  Jos\u00e9 Vaquero l\u00f3pez (vocal)<\/li>\n<li>arasu Ganesan (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Miriam Ruiz Serrano Las welwitindolinonas constituyen un grupo de alcaloides de gran inter\u00e9s qu\u00edmico y farmacol\u00f3gico, tanto [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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