Vinylstannylated alkylating agents as prosthetic groups for radioiodination of small molecules: design, synthesis, and application to iodoallyl analogues of spiperone and diprenorphine.
The preparation and synthetic utility of p-toluenesulfonate esters of (E)- and (Z)-3-(tri-n-butylstannyl)-prop-2-en-1-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.
Musachio
J L
JL
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205-2179.
Lever
J R
JR
D000477:Alkylating Agents / Q000138:chemical synthesis / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000737:chemistry; D004174:Diprenorphine / Q000031:analogs & derivatives* / Q000737:chemistry; D004951:Esterification; D007457:Iodine Radioisotopes; D009682:Magnetic Resonance Spectroscopy; D013134:Spiperone / Q000031:analogs & derivatives* / Q000737:chemistry
D000477:Alkylating Agents; D003432:Cross-Linking Reagents; D007457:Iodine Radioisotopes; D004174:Diprenorphine; D013134:Spiperone