Nitroepoxides to diamines and synthesis of nitrobenzofurazans as p38 map kinase inhibitors
- Autores: Juan Agut Gregori
- Directores de la Tesis: Florenci Vicent González Adelantado (codir. tes.), Santiago Rodríguez Pastor (codir. tes.)
- Lectura: En la Universitat Jaume I ( España ) en 2014
- Idioma: español
- Tribunal Calificador de la Tesis: Miquel Angel Pericàs (presid.), Steve Bull (secret.), Gonzalo Blay Llinares (voc.)
- Materias:
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- Resumen
Anti-vicinal diamines can be prepared in a highly diastereoselective fashion when nitroepoxides are first treated with benzylamine and then with a reducing agent. This procedure represents a convenient method to prepare vicinal diamines from easily accessible starting compounds. When chiral L--alpha-methyl benzylamine is utilized in this process, a new DYKAT is operative, which subsequently affords a facile and highly selective method for the preparation of enantio- and diastereomerically pure anti-1,2-diamines. This method represents a one-pot procedure that starts with formation of amino imines as a diastereomeric mixture from a racemic mixture of nitroepoxides and concludes with a reduction to furnish a single enantiomer through a dynamic kinetic asymmetric transformation. In terms of ease of preparation, this protocol to access diamines can be accessed directly from nitroalkenes in a one-pot sequence. This process provides a convenient method for the generation of important 1,2-diamines and highlights the synthetic versatility of racemic nitroepoxides as useful synthons.
The second part of the work is focused on the preparation of p38 MAPK docking-groove-targeted compounds, which are derivatives of two structures optimized by docking: compounds 6946893 and 5380, as inhibitors of inflammatory hyperalgesia. Several synthesized compounds of the benzo-oxadiazol family are potent inhibitors of cytokine production in human monocytic cells. In addition, a member of this family, N-(5-chloro-2-methylphenyl)-7-nitrobenzo[c][1,2,5]oxadiazol-4-amine, inhibits inflammatory and post-inflammatory pain in murine models.
