An Efficient Synthesis of<i>N</i>-Methyl Amino Acids by Way of Intermediate 5-Oxazolidinones

Abstract

N-Methyl amino acids occur in many natural products. Experimental strategies are presented for a unified approach to the synthesis of N-methyl derivatives through 5-oxazolidinones of the 20 common l-amino acids. The amino acids with reactive side chains that required protecting groups or devoted syntheses for side chain construction for N-methylation to proceed included serine, threonine, tyrosine, cysteine, methionine, tryptophan, asparagine, histidine, and arginine. The studies have provided improved methods for the preparation of N-methyl serine, threonine, and tyrosine. All 20 of the common l-amino acids are now available in suitable forms for solid or solution-phase peptide synthesis.