Site-Selective Methylation of N^β-Nosyl Hydrazides of N-Nosyl Protected α-Amino Acids

Abstract

The methylation reaction of N(beta)-nosyl hydrazides of N-nosyl protected alpha-amino acids by using diazomethane shows a controlled regiochemical trend and makes it possible to obtain the corresponding products methylated at specific positions depending on the amount of diazomethane used. The observed selectivity is closely connected with the different acidity of sulfonyl hydrazide, sulfonamide, and acyl hydrazine protons present in the analyzed substrates. The reactivity order of these three diverse reactive sites is supported by theoretical calculations. The hydrazine derivatives considered in this work belong to a class of compounds with interesting biological activity and of great interest in organic synthesis.

Sustainable Production of N-methylphenylalanine by Reductive Methylamination of Phenylpyruvate Using Engineered Corynebacterium glutamicum

“…Chemical synthesis of N-methylated amino acids via several routes is known, including ring opening of 5-oxazolidinones, direct methylation and reductive amination [8,19,20]. However, chemical synthesis of N-methylated amino acids often uses toxic reagents and is limited by incomplete enantiopurity, low product yields or over-methylation [8,19].…”

Fermentative N-Methylanthranilate Production by Engineered Corynebacterium glutamicum

“…Chemical synthesis of free N -alkylated amino acids is well studied, and various routes are known, such as by nucleophilic substitution of α-bromo acids, N -methylation of sulfonamides, carbamates or amides, reduction of Schiff bases generated with an amino acid and formaldehyde or other aldehydes, by direct alkylation of protected amino acids or by ring-opening of 5-oxazolidinones [ 6 , 7 , 8 , 9 ]. However, these processes are often limited by low product yields, over-methylation, toxic reagents, or their incomplete enantiopurity [ 10 , 11 ].…”