Synthesis of 2-C-14-iminothiolane and 2-C-13, N-15-iminothiolane (Traut's reagent)

摘要

2-Iminothiolane has found utility in the growing area of antibody-drug conjugates by serving as a lysine-thiolating agent and the junction between the antibody and the cytotoxic payload during random conjugation of a monoclonal antibody. 2-C-14-Iminothiolane was prepared from commercially available [C-14]KCN using a four-step sequence in an overall 10% radiochemical yield. Stable-labeled 2-C-13, N-15-iminothiolane was also prepared from [(CN)-C-13-N-15]KCN in a similar manner. The. labeled Traut's reagent produced by this sequence showed comparable reactivity as the commercially available unlabeled reagent with a representative monoclonal antibody and could serve as highly informative analytical tools to investigate antibody-drug conjugate formation via the random conjugation process.