Reacciones de metátesis e hidrotiolación como herramientas sintéticas para la obtención de compuestos con interés biológico

This thesis is focused on the study of reactivity of unsaturated systems, both alkenes and alkynes, to provide other more complex systems with a biological interest. For this purpose, metathesis and hydrothiolation reactions have been used as key steps. In the first part of this report, we performed a thorough study of the metathesis reaction on 7-azanorbornene systems. Ring rearrangement metathesis (RRM) in N-acyl-1-substituted-7-azanorbornene derivatives was carried out in different reaction conditions to achieve bicyclic lactams and a novel spirocyclic system with pyrrolizidine, indolizidine and pyrrole[1,2a]azepine substructures. In the second part, we applied the cross metathesis reaction (CM) to obtain a family of neoglycoaminoacid derivatives with a linker, which is generated in the CM process, and used to separate the sugar moiety of the amino acid residue. The conformational analysis of these new neoglycoconjugates showed the high flexibility of the carbohydrate moiety in comparison to the more restricted spatial arrangement of these carbohydrates in natural glycoaminoacids. Having in mind we were unable to make use of CM reaction employing N-acetyl-D-galactosamine (GalNAc), we decided to create the linker from hydrothiolation reaction, applied to alkenes (TEC) and alkynes (TYC). Depending on starting materials, the final compound can present one or two sugars on the side chain of the amino acid. Afterwards, these neoglycoaminoacids have been incorporated into an epitope of recognition of a mucin-like glycoprotein (MUC1) with the APDTRP sequence. Sugar moieties linked to backbone were not able to fix a specific conformation, as it was deduced from conformational analysis. Additionally, affinity studies between lectins and the neoglycoconjugates with a sole carbohydrate were carried out, showing that the new elongated compounds had a similar behavior than the observed in the natural epitope of serine. Finally, we were able to elucidate the X-ray structure of one of our neoglycopeptides associated with the scFV fragment of SM3 antibody.

Grantor dc:publisher

Universidad de La Rioja (España)

Year dc:date

2016

Author dc:creator

• Rojas Ocáriz, Víctor

Contributors dc:contributor

• Avenoza Aznar, Alberto (Universidad de La Rioja)
• Busto Sancirián, Jesús Héctor (Universidad de La Rioja)

Statement dc:rights

• LICENCIA 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. Más información: https://dialnet.unirioja.es/info/derechosOAI | INTELLECTUAL PROPERTY RIGHTS STATEMENT: Full text documents hosted by Dialnet are protected by copyright and/or related rights. This digital object is accessible without charge, but its use is subject to the licensing conditions set by its authors or editors. Unless expressly stated otherwise in the licensing conditions, you are free to linking, browsing, printing and making a copy for your own personal purposes. All other acts of reproduction and communication to the public are subject to the licensing conditions expressed by editors and authors and require consent from them. Any link to this document should be made using its official URL in Dialnet. More info: https://dialnet.unirioja.es/info/derechosOAI

Language dc:language

spa

Repository record dc:identifier

https://dialnet.unirioja.es/servlet/oaites?codigo=48495

OAI identifier oai:identifier

oai:dialnet.unirioja.es:TES0000010674