Alkyl Thiocyanurates as Thioester Mimetics. Transthioesterification and Ligation Reactions with High Potential in Dynamic Covalent Chemistry

Alkyl thiocyanurates,
the compounds formed in the SN reaction of
thiocyanuric acid and alkyl halides, are susceptible to transthioesterification
and ligation with molecules containing cysteamine, analogous to native
chemical ligation of thioesters with peptides with an N-terminal cysteine
moiety. The ligation is irreversible and results in the formation
of mono- and disubstituted products dominantly. Transthioesterification,
in contrast, is fully reversible and may be used in constructing dynamic
systems. The application of this reactivity in dynamic covalent chemistry
has been exemplified by the preparation of a library of mixed thiocyanurates
of glutathione and thioglycolic acid with self-assembly abilities
and metathesis between thiocyanurates of tris(carboxymethyl) and tris(carboxamidomethyl)
catalyzed by MESNa (sodium 2-mercaptoethylsulphonate) or MPAA (4-mercaptophenylacetic
acid). Differences in reactivity of thiocyanurates toward cysteamines
and thiols has been explained based on conceptual DFT.