N-methyl-N-nosyl-beta(3)-amino acids.
N-Methyl-beta(3)-amino acids are important building blocks in the synthesis of biologically active molecules. A very simple and efficient approach to transform natural alpha-amino acids into their corresponding N-methyl-beta(3)-amino acids is here presented. In the method, the key intermediates N-methyl-N-nosyl-alpha-aminoacyldiazomethanes are prepared in only one step, by a simple treatment of the corresponding N-nosyl-alpha-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-beta(3)-amino acids. The Wolff rearrangement of N-methyl-N-nosyl-alpha-aminoacyldiazomethanes provides the corresponding N-methyl-N-nosyl-beta(3)-amino acids with total retention of the chiral configuration of the starting alpha-amino acids. No epimerization of the chiral carbon atom is observed also when N-methyl-N-nosyl-beta(3)-amino acids are transformed into chlorides and coupled with alpha-amino acid methyl esters to achieve model scaffolds for biologically important modified peptides.
Belsito
Emilia
E
Dipartimento di Scienze Farmaceutiche, Università della Calabria, Via P. Bucci, Cubo 15/C, I-87036 Arcavacata di Rende (CS) - Italy.
Di Gioia
Maria L
ML
Greco
Antonella
A
Leggio
Antonella
A
Liguori
Angelo
A
Perri
Francesca
F
Siciliano
Carlo
C
Viscomi
Maria C
MC
D000586:Amination; D000596:Amino Acids / Q000737:chemistry*; D003978:Diazomethane / Q000138:chemical synthesis / Q000737:chemistry; D008745:Methylation; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry
D000596:Amino Acids; D010455:Peptides; D003978:Diazomethane