N-Methyl-N-nosyl-β~3-amino Acids

摘要

N-Methyl-β~3-amino acids are important building blocks in the synthesis of biologically active molecules. A very simple and efficient approach to transform natural α-amino acids into their corresponding N-methyl-β~3-amino acids is here presented. In the method, the key intermediates N-methyl-N-nosyl-α-aminoacyl-diazomethanes are prepared in only one step, by a simple treatment of the corresponding N-nosyl-α-aminoacyl chlorides with diazomethane. The synthetic route takes advantage from the use of the nosyl group. This N-masking moiety activates the NH function, and the N-methylation can directly occur during the acylation step of diazomethane, rendering useless a second step that instead is shown to be necessary in all the classical procedures already reported for the preparation of N-methyl-β~3-amino acids. The Wolff rearrangement of N-methyl-N-nosyl-α-aminoacyldiazomethanes provides the corresponding N-methyl-N-nosyl-β~3-amino acids with total retention of the chiral configuration of the starting α-amino acids. No epimerization of the chiral carbon atom is observed also when N-methyl-N-nosyl-β~3-amino acids are transformed into chlorides and coupled with α-amino acid methyl esters to achieve model scaffolds for biologically important modified peptides.