A New Method for Synthesizing α-Amino Acid N-Carboxy Anhydride (NCA)

Abstract

A New method for synthesizing α-amino acid N-carboxy anhydride (NCA) was described, which uses trichloromethyl chloroformate (TCF) instead of phosgene in the Fuchs-Farthing method.
In this paper, γ-methyl-L-glutamate (MLG) was used as one of α-amino acids. Experimental conditions for this new reaction were almost the same as those of the Fuchs-Farthing method. The quality and yield of the NCA obtained were high, but after the reaction it was necessary to add carbon into the reaction mixture and stir for several ten minutes for the purpose of decomposing the unreacted TCF into phosgene gas ; the phosgene gas formed was purged from the reaction mixture by streaming nitrogen gas at the end of the reaction. Solvent systems of ethylenedichloride (EDC) -tetrahydrofurane, EDC-dioxane (DOX), EDC-ethylacetate and EDC-methylacetate were found to be suitable.The ratio of the solvent (ml) /MLG (gr) was as low as 8 in the case of the EDC-DOX solvent system.