Chemical Methods for N‐ and O‐Sulfation of Small Molecules, Amino Acids and Peptides

Sulfation of the amino acid residues of proteins is a significant post‐translational modification, the functions of which are yet to be fully understood. Current sulfation methods are limited mainly to O‐tyrosine (sY), which requires negatively charged species around the desired amino acid residue and a specific sulfotransferase enzyme. Alternatively, for solid‐phase peptide synthesis, a de novo protected sY is required. Therefore, synthetic routes that go beyond O‐sulfation are required. We have developed a novel route to N‐sulfamation and can dial‐in/out O‐sulfation (without S‐sulfurothiolation), mimicking the initiation step of the ping‐pong sulfation mechanism identified in structural biology. This rapid, low‐temperature and non‐racemising method is applicable to a range of amines, amides, amino acids, and peptide sequences. A general sulfation/sulfamation strategy: A new method to selectively N‐sulfamate or O‐sulfate molecules is reported that mimics the initiation step of the ping‐pong sulfation mechanism identified in structural biology. A rapid, low‐temperature, non‐racemising approach to functionalise amino acids and peptides is demonstrated.