Towards enantiomerically pure β-seleno-α-amino acids via stereoselective Se-Michael addicions to chiral dehydroalanines

Résumé

Selenium plays a crucial role in different biological processes, being necessary for theproper functioning of the human body. Therefore, selenium compounds have becomemolecules of great interest due to their antiviral and anticancer activities and their use as naturalfood supplements.Selenocysteine (Sec) is the 21st genetically encoded amino acid and plays an importantrole in protein folding and stability, conferring interesting redox properties. In addition, protectedselenocysteine derivatives are used as precursors of dehydroalanine, which allows theintroduction of various post-translational modifications. On the other hand, some aryl derivativesof Se serve as chemical models for the inhibition of selenoenzymes, which has implications forcancer therapy. Beyond applications in bioconjugation, selenoamino acids are especiallyrelevant in Native Chemical Ligation (NCL).[1]Although the nucleophilic substitution reaction has been widely employed for thesynthesis of these Sec derivatives, 1,4-conjugate addition has been less explored, especiallythe stereoselective 1,4-conjugate addition of Se-nucleophiles to chiral Michael acceptors.Therefore, in this work, we aim to extend the methodology established by our research group[2]to the synthesis of enantiomerically pure selenoamino acids. The key step of such synthesis isthe attack of different Se-nucleophiles to a chiral dehydroalanine, to obtain a singlediastereoisomer. The methodology is simple and does not require the use of any catalyst,providing excellent yields at room temperature. Subsequent facile acid hydrolysis of the abovediastereoisomers leads to the corresponding selenoamino acids