Syntheses of methylcarbamoylated amino acids using synthetic equivalents of methyl isocyanate

Abstract

A simple environmentally friendly one-step synthetic procedure was developed for S- and N-methylcarbamoylation of amino acids and their derivatives in buffered aqueous solutions. N-Succinimidyl N-methylcarbamate (SNMC) and N,S-dimethylthiocarbamate (DMTC) were used as synthetic equivalents to replace highly hazardous methyl isocyanate (MIC). SNMC reacted rapidly in both S- and N-methylcarbamoylations affording nearly quantitative conversions (>97 %) of all tested compounds after 2–3 h at 50 °C at pH 8.2 and 9.5–10 for S- and N-methylcarbamoylations, respectively. Under the same conditions, DMTC reacted more slowly (48 h for N-methylcarbamoylations) but with some polar amino acids it provided products of higher purity than SNMC. Similarly, N-trideuteriomethyl-S-methylthiocarbamate (DMTC-d₃) was used to synthesize N_α- and N_ε-trideuteriomethylcarbamoyl derivatives of valine and lysine, respectively. Prepared compounds will be used in toxicological research as authentic standards in the analyses for protein adducts derived from MIC or its metabolic precursor, N,N-dimethylformamide.

Graphical Abstract

Keywords:

• Methylcarbamoylation
• synthetic equivalent of methyl isocyanate
• N,N-dimethylformamide
• methyl isocyanate
• globin adducts

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This work was supported by grant NV19-09-00378 from the Czech Ministry of Health.