Synthesis of Novel Nonproteinogenic Amino Acids: N-Ethyl-α,β-dehydroamino Acid Methyl Esters

Two routes for the synthesis of N-ethyl-N-(4-nitrophenylsulfonyl)-alpha,beta-dehydroamino acid derivatives from serine, threonine and phenylserine derivatives are presented. One route consists of dehydration of N-(4-nitrophenylsulfonyl)-beta-hydroxyamino acid esters with di-tert-butyl dicarbonate catalyzed by 4-(dimethylamino)pyridine, followed by alkylation of the N-(4-nitrophenylsulfonyl)-alpha,beta-dehydroamino acid methyl esters obtained with triethyloxonium tetrafluoroborate. The second strategy applied the same procedures but in inverse order: alkylation followed by dehydration. These methods made it possible to obtain for the first time, new non-natural amino acids, which incorporate both an N-ethyl and an alpha,beta-dehydro moiety.