Síntesis y reactividad de sulfamidatos cíclicos derivados de aminoácidos
This PhD Thesis is focused on obtaining a library of α- and β-amino acids by opening different cyclic sulfamidates in a stereospecific and regioselective manner. Thus, an study of the synthesis and reactivity of different amino acid-derived cyclic sulfamidates against nucleophiles of different nat...
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Universidad de La Rioja (España)
2021
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This PhD Thesis is focused on obtaining a library of α- and β-amino acids by opening different cyclic sulfamidates in a stereospecific and
regioselective manner. Thus, an study of the synthesis and reactivity of different amino acid-derived cyclic sulfamidates against nucleophiles of
different nature has been carried out.
Firstly, in chapter 3 a library of cyclic sulfamidates derived from amino acids and protected in different ways is presented, to be used as starting
products in other chapters. For this purpose, already published methods are replicated or modified to scale them up, simplify them or obtain new
sulfamidates.
In chapter 4, the reactivity of several cyclic sulfamidates derived from different amino acids towards O-carbohydrates is studied. In this way, their
reactivity is compared depending on their structure, obtaining good results in the openings of a cyclic sulfamidate derived from α-methylserine. In
addition, an analogue of the TN antigen, present in cancer-related processes, is synthesized.
In Chapter 5, the opening of cyclic sulfamidates with peptides is carried out. First, the behavior of serine-derived sulfamidates in nucleophilic
openings with peptides in the presence of base is evaluated. On the other hand, in collaboration with Dr. De Luca's group, a methodology based
on the use of molecular sieve is used to avoid undesired elimination reactions. This methodology allows obtaining a library of peptides containing
different lanthionines in their structure.
In order to broaden the applications of cyclic sulfamidates towards obtaining new β2,2-amino acids, throughout chapter 6, a new methodology to
obtain different α-alkylisoserines is developed. For this purpose, the synthesis and alkylation of bicyclic N,O-acetals derived from isoserine, which
allow after their hydrolysis the obtaining of several enantiomerically pure (R)- and (S)-alkylisoserines, is studied theoretically and experimentally.
Finally, from (R)-α-benzylisoserine, in Chapter 7, a new cyclic sulfamidate is obtained from which, by means of its nucleophilic opening with
nucleophiles of different nature, new β2,2-amino acids are obtained. |
| author2 |
Busto Sancirián, Jesús Héctor (Universidad de La Rioja) |
| author_facet |
Busto Sancirián, Jesús Héctor (Universidad de La Rioja) Tovillas Greca, Pablo |
| format |
text (thesis) |
| author |
Tovillas Greca, Pablo |
| spellingShingle |
Tovillas Greca, Pablo Síntesis y reactividad de sulfamidatos cíclicos derivados de aminoácidos |
| author_sort |
Tovillas Greca, Pablo |
| title |
Síntesis y reactividad de sulfamidatos cíclicos derivados de aminoácidos |
| title_short |
Síntesis y reactividad de sulfamidatos cíclicos derivados de aminoácidos |
| title_full |
Síntesis y reactividad de sulfamidatos cíclicos derivados de aminoácidos |
| title_fullStr |
Síntesis y reactividad de sulfamidatos cíclicos derivados de aminoácidos |
| title_full_unstemmed |
Síntesis y reactividad de sulfamidatos cíclicos derivados de aminoácidos |
| title_sort |
síntesis y reactividad de sulfamidatos cíclicos derivados de aminoácidos |
| publisher |
Universidad de La Rioja (España) |
| publishDate |
2021 |
| url |
https://dialnet.unirioja.es/servlet/oaites?codigo=297366 |
| work_keys_str_mv |
AT tovillasgrecapablo sintesisyreactividaddesulfamidatosciclicosderivadosdeaminoacidos |
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1718437098620452864 |
| spelling |
oai-TES00000230152021-11-30Síntesis y reactividad de sulfamidatos cíclicos derivados de aminoácidosTovillas Greca, PabloThis PhD Thesis is focused on obtaining a library of α- and β-amino acids by opening different cyclic sulfamidates in a stereospecific and regioselective manner. Thus, an study of the synthesis and reactivity of different amino acid-derived cyclic sulfamidates against nucleophiles of different nature has been carried out. Firstly, in chapter 3 a library of cyclic sulfamidates derived from amino acids and protected in different ways is presented, to be used as starting products in other chapters. For this purpose, already published methods are replicated or modified to scale them up, simplify them or obtain new sulfamidates. In chapter 4, the reactivity of several cyclic sulfamidates derived from different amino acids towards O-carbohydrates is studied. In this way, their reactivity is compared depending on their structure, obtaining good results in the openings of a cyclic sulfamidate derived from α-methylserine. In addition, an analogue of the TN antigen, present in cancer-related processes, is synthesized. In Chapter 5, the opening of cyclic sulfamidates with peptides is carried out. First, the behavior of serine-derived sulfamidates in nucleophilic openings with peptides in the presence of base is evaluated. On the other hand, in collaboration with Dr. De Luca's group, a methodology based on the use of molecular sieve is used to avoid undesired elimination reactions. This methodology allows obtaining a library of peptides containing different lanthionines in their structure. In order to broaden the applications of cyclic sulfamidates towards obtaining new β2,2-amino acids, throughout chapter 6, a new methodology to obtain different α-alkylisoserines is developed. For this purpose, the synthesis and alkylation of bicyclic N,O-acetals derived from isoserine, which allow after their hydrolysis the obtaining of several enantiomerically pure (R)- and (S)-alkylisoserines, is studied theoretically and experimentally. Finally, from (R)-α-benzylisoserine, in Chapter 7, a new cyclic sulfamidate is obtained from which, by means of its nucleophilic opening with nucleophiles of different nature, new β2,2-amino acids are obtained.Esta Tesis Doctoral está centrada en la obtención de una librería de α- y β-aminoácidos mediante la apertura de diferentes sulfamidatos cíclicos de manera estereoespecífica y regioselectiva. De esta manera, se ha llevado a cabo un estudio de la síntesis y reactividad de diferentes sulfamidatos cíclicos derivados de aminoácidos frente a nucleófilos de diversa naturaleza. En primer lugar, en el capítulo 3 se presenta una librería de sulfamidatos cíclicos derivados de aminoácidos y protegidos de diversas maneras, para emplearlos como productos de partida en otros capítulos. Para ello, se replican o modifican métodos ya publicados para escalarlos, simplificarlos u obtener nuevos sulfamidatos. En el capítulo 4, se estudia la reactividad de varios sulfamidatos cíclicos derivados de distintos aminoácidos frente a O-carbohidratos. De esta manera, se compara la reactividad de los mismos dependiendo de su estructura, obteniendo buenos resultados en las aperturas de un sulfamidato cíclico derivado de α-metilserina. Además, se sintetiza un análogo del antígeno TN, presente en procesos relacionados con el cáncer. En el capítulo 5, se lleva a cabo la apertura de sulfamidatos cíclicos con péptidos. En primer lugar, se evalúa el comportamiento de sulfamidatos derivados de serina en aperturas nucleófilas con péptidos en presencia de base. Por otro lado, colaborando con el grupo de la Dra. De Luca, se utiliza una metodología basada en el empleo de tamiz molecular para evitar reacciones de eliminación no deseadas. Dicha metodología permite obtener una librería de péptidos que contienen en su estructura diferentes lantioninas. Con el fin de ampliar las aplicaciones de los sulfamidatos cíclicos hacia la obtención de nuevos β2,2-aminoácidos, a lo largo del capítulo 6 se desarrolla una nueva metodología para obtener diferentes α-alquilisoserinas. Para ello, se estudia de manera teórica y experimental, la síntesis y alquilación de N,O-acetales bicíclicos derivados de isoserina, que permiten tras su hidrólisis la obtención de varias (R) y (S)-alquilososerinas enantioméricamente puras. Finalmente, a partir de (R)-α-bencilisoserina, en el capítulo 7, se obtiene un nuevo sulfamidato cíclico a partir del cual, mediante su apertura nucleófila con nucleófilos de diversa naturaleza se obtienen nuevos β2,2-aminoácidos.Universidad de La Rioja (España)Busto Sancirián, Jesús Héctor (Universidad de La Rioja)Jiménez Oses, Gonzalo (Universidad de La Rioja)2021text (thesis)application/pdfhttps://dialnet.unirioja.es/servlet/oaites?codigo=297366spaLICENCIA DE USO: Los documentos a texto completo incluidos en Dialnet son de acceso libre y propiedad de sus autores y/o editores. Por tanto, cualquier acto de reproducción, distribución, comunicación pública y/o transformación total o parcial requiere el consentimiento expreso y escrito de aquéllos. Cualquier enlace al texto completo de estos documentos deberá hacerse a través de la URL oficial de éstos en Dialnet. 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