An Efficient Synthesis of Optically Pure N δ-Monomethylated l-Arginine and l-Ornithine

Abstract

N ω-Methylated L-arginines such as asymmetric dimethyl-L-arginine (ADMA) and monomethyl-L-arginine (NMMA) are well-known endogenous modulators of the nitric oxide (NO) generating system. To understand the (patho)physiological role and impact of N δ-methylation of L-arginine and L-ornithine an efficient synthesis of the pure enantiomers was needed. A synthetic approach that furnished both the desired amino acids in 8-10 steps from commercially available N-Boc-L-ornithine in good overall yields (20-21%) and with high optical purity (>99% ee) is reported.