[1][2][3] NCAs are typically prepared by phosgenation of amino acids:[4] They were first synthesized by Hermann Leuchs by heating an N-ethoxycarbonyl or N-methoxycarbonyl amino acid chloride in a vacuum at 50-70 °C:[5][6] A moisture-tolerant route to unprotected NCAs employs epoxides as scavengers of hydrogen chloride.

Of several improvements, one notable procedure involves treating an unprotected amino acid with phosgene or its trimer.

[8][4][9] NCAs are prone to hydrolysis to the parent amino acid: Some derivatives however tolerate water briefly.

[7] NCAs convert to homopolypeptides ( [N(H)CH(R)CO)]n) through ring-opening polymerization:[1][2][3][10][11][12][13] Poly-L-lysine has been prepared from N-carbobenzyloxy-α-N-carboxy-L-lysine anhydride, followed by deprotection with phosphonium iodide.

[14] Peptide synthesis from NCAs does not require protection of the amino acid functional groups.