Vinylstannylated Alkylating Agents as Prosthetic Groups for Radioiodination of Small Molecules: Design, Synthesis, and Application to Iodoallyl Analogs of Spiperone and Diprenorphine

The preparation and synthetic utility of p-toluenesulfonate esters of (E)-and (Z)-3-(tri-n-butylstannyl)-prop-2-en-l-ol as bifunctional reagents for radioiodination are described. These vinylstannylated alkylating agents are prepared in two steps from propargyl alcohol, and readily couple with nucleophilic functionality (amide nitrogen, secondary amine, tertiary alcohol) in good yields (48-95 %) to provide derivatives of the neuroreceptor ligands spiperone and diprenorphine. Regio-and stereospecific radioiododestannylation with retention of configuration occurs under mild, no-carrier-added conditions to give the corresponding radiolabeled N-or O-iodoallyl analogues in good radiochemical yields (55-95 %) with high specific radioactivities. The methodology is versatile and well-suited to selective labeling of small molecules with radioisotopes of iodine such as ¹²⁵I or ¹²³I.