title: Synthesis of 2-(14)C-iminothiolane and 2-(13)C,(15)N-iminothiolane (Traut's reagent).
abstract: 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-(14)C-Iminothiolane was prepared from commercially available [(14)C]KCN using a four-step sequence in an overall 10% radiochemical yield. Stable-labeled 2-(13)C,(15)N-iminothiolane was also prepared from [(13)C(15)N]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.
authors.affiliation: Discovery Chemistry Platforms-Radiochemistry, Bristol-Myers Squibb, P.O. Box 4000, Princeton, NJ, 08543, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wallace
authors.affiliation: Discovery Chemistry Platforms-Radiochemistry, Bristol-Myers Squibb, P.O. Box 4000, Princeton, NJ, 08543, USA.
authors.forename: Alban J
authors.initials: AJ
authors.lastname: Allentoff
authors.affiliation: Discovery Chemistry Platforms-Radiochemistry, Bristol-Myers Squibb, P.O. Box 4000, Princeton, NJ, 08543, USA.
authors.forename: John
authors.initials: J
authors.lastname: Brailsford
authors.affiliation: Discovery Chemistry Platforms-Radiochemistry, Bristol-Myers Squibb, P.O. Box 4000, Princeton, NJ, 08543, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Gong
authors.affiliation: Discovery Chemistry Platforms-Radiochemistry, Bristol-Myers Squibb, P.O. Box 4000, Princeton, NJ, 08543, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Bonacorsi
authors.affiliation: Pharmaceutical Research and Development, Bristol-Myers Squibb, 1 Squibb Dr, New Brunswick, NJ, 08903, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Rinaldi
mesh_terms: D002250:Carbon Radioisotopes / Q000737:chemistry*; D007096:Imidoesters / Q000138:chemical synthesis* / Q000737:chemistry; D009587:Nitrogen Isotopes / Q000737:chemistry*
chemical_list: D002250:Carbon Radioisotopes; D007096:Imidoesters; D009587:Nitrogen Isotopes; C005905:methyl 4-mercaptobutyrimidate
keywords: 2-iminothiolane; Traut's reagent; methyl 4-mercaptobutyrimidate; monoclonal antibodies