Methyl isocyanate conjugates

Slatter JG, Rashed MS, Pearson PG, et al. Biotransformation of methyl isocyanate in the rat. Evidence for glutathione conjugation as a major pathway of metabolism and implications for isocyanate-mediated toxicities. Chem Res Toxicol 1991 4(2) 157—161. 

The rearrangements 67 —> 70, 71 —> 72 and 74 —> 75 include the transformation of conjugated dienes to cumulenes. Nevertheless, these reactions take place with very high yields in some cases, because either an irreversible step of hydrolysis such as 69 —> 70 is involved or the very exothermic transformation from cyanates to isocyanates is used. Comparison of the energies, calculated by ab initio methods [121], shows that, for example, the energy of methyl isocyanate is lower than that of methyl cyanate by 26.8 kcal mol-1 and that of vinyl isocyanate is lower than that of vinyl cyanate by 28.1 kcal mol-1. 

Pearson, PG., Slatter, J.G., Rashed, M.S., Han, D.H., Baillie, T.A. (1991). Carbamoylation of peptides and proteins in vitro by S-(N-methylcarbamoyl)GSH and S-(N-methylcarbamoyl)cysteine, two electrophilic S-linked conjugates of methyl isocyanate. Chem. Res. Toxicol. 4 436-44. 

Figure 12. A library of 54 neamine conjugates was constructed using a solution phase multicomponent condensation strategy. A protected neamine aldehyde derivative was condensed with two isocyanates and thirteen protected amino acids to produce the PEG linked products. Cleavage from the PEG support and protecting group removal gave the neamine conjugates as either the free acid or methyl ester.

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