Facile Synthesis Of Dehydroalanine Amides And Esters And Their Michael Addition Of N-nucleophiles

Dehydroamino acids are highly important in use as key constituents of severial biologically and pharmacologically active compounds, such as nisin, inhibitors of renin and peptide antibiotics, as well as precursors to several unnatural amino acids and elements determining the conformation of peptides. Great interest has been currently focused on the β-substituted alanine derivatives, particularly 2,3-diaminopropanoic acid derivatives, as they are crucial compositions of bleomycin and capreomycin. Physiological significance varies with the changing of the two amino substitution groups of β-substituted alanine derivatives, which has largely spurred the development of synthetic strategies for these compounds and improvement of methodologies for differentiating the two amino groups.In this dissertation, Boc- Δ Ala-OCH₃ was successfully synthesized from three distinct serine derivatives with high yield. And effects of preparative factors such as bases and solvents to the final product yielding have been elaborately investigated. It's well known that 2-aminoenals, seems to play an important role in living systems, used to be prepared via nucleophilic substitution of 2-haloenals by secondary amines. Herein, we presented a new applicable route to the synthesis of 2-Boc-aminoenals by the reduction of Boc- Δ Ala-OCH₃. At the same time, some other dehydroalanine esters and amides were readily synthesized by two distinctive methods. Since dehydroalanine derivatives are quite reactive, Michael addition of N-nucleophiles to these derivatives have also been readily carried out. Results showed that the addition products of dehydroalanine esters were unstable and addition reaction of dehydroalanine amides was feasible with moderate yield.