Síntesis y reactividad de sulfamidatos cíclicos derivados de aminoácidos

Resumen

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.