Synthesis of new n-ethyl dehydroamino acid derivatives : n-ethyl β,β-dibromo, n-ethyl β-bromo β-substituted, n-ethyl β,β-disubstituted n-protected dehydroamino acid methyl esters

Abstract

Recently we reported the use of a sequence of alkylation and dehydration methodologies to obtain from the methyl esters of N-(4-nitrophenylsulfonyl)-β-hydroxyamino acids, new non-proteinogenic amino acids, namely, N-ethyl-α,β-dehydroamino acids. Thus, it was possible to obtain for the first time, non-natural amino acids which incorporate both the N-ethyl and α,β-dehydro moieties. Herein, we report the application of this N-alkylation procedure to several methyl esters of β,β-dibromo and β-bromo, β-substituted dehydroamino acids protected with standard amine protecting groups such as tert-butyloxycarbonyl, benzyloxycarbonyl and 4-nitrobenzyloxycarbonyl as well as acyl and sulfonyl groups. The procedure allows the synthesis of the methyl esters of N-protected, N-ethyl, β,β-dibromo and N-ethyl, β-bromo, β-substituted dehydroamino acids in fair to high yields. Some of these N-ethylated dehydroamino acid derivatives were used as substrates in cross coupling reactions to give N-ethyl, β,β-disubstituted dehydroalanine derivatives.