An efficient preparation of N-methyl-alpha-amino acids from N-nosyl-alpha-amino acid phenacyl esters.
In this paper we describe a simple and efficient solution-phase synthesis of N-methyl-N-nosyl-alpha-amino acids and N-Fmoc-N-methyl-alpha-amino acids. This represents a very important application in peptide synthesis to obtain N-methylated peptides in both solution and solid phase. The developed methodology involves the use of N-nosyl-alpha-amino acids with the carboxyl function protected as a phenacyl ester and the methylating reagent diazomethane. An important aspect of this synthetic strategy is the possibility to selectively deprotect the carboxyl function or alternatively both amino and carboxyl moieties by using the same reagent with a different molar excess and under mild conditions. Furthermore, the adopted procedure keeps unchanged the acid-sensitive side chain protecting groups used in Fmoc-based synthetic strategies.
Leggio
Antonella
A
Dipartimento di Scienze Farmaceutiche, Università della Calabria, Via Ponte P. Bucci Cubo 15/C, I-87036 Arcavacata di Rende (CS), Italy.
Belsito
Emilia Lucia
EL
De Marco
Rosaria
R
Liguori
Angelo
A
Perri
Francesca
F
Viscomi
Maria Caterina
MC
D000098:Acetophenones / Q000737:chemistry*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004952:Esters; D007202:Indicators and Reagents / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D012996:Solutions / Q000737:chemistry; D013237:Stereoisomerism
D000098:Acetophenones; D000596:Amino Acids; D004952:Esters; D007202:Indicators and Reagents; D010455:Peptides; D012996:Solutions