Improved synthesis of (5Z)-7-3-endo-{(benzenesulfonamido)-bicyclo[2.2.1]heptyl}hept-5-enoic acid (S-145) derivatives and their iodine-125-labeled radioligands for the study of thromboxane A2 receptor

Article abstract of DOI:10.1016/0009-3084(93)90081-D

An improved synthetic scheme for (5Z)-7-{3-endo-[(benzenesulfonamido)-bicyclo[2.2.1]heptyl}-hept-5-enoic acid (S145) and its analogs has been designed. The procedure involves direct sulfonylation of 2-allyl-3-aminobicyclo[2.2.1]heptane intermediate followed by ozonolysis and addition of a C5 carboxyl unit. The yield of the final product was significantly improved. (5Z)-7-{3-endo-[(4-iodobenzensulfonamido)-bicyclo [2.2.1]heptyl}hept-5-enoic acid (HS-145) and (5Z)-7-{3-endo-[(4-hydroxy-benzensulfonamido)-bicyclo [2.2.1]heptyl}hept-5-enoic acid (HS-145) were synthesized directly without any protection and deprotection steps. [¹²⁵I](5Z)-7-{3-endo-[(4-iodobenzensulfonamido)- bicyclo[2.2.1]heptyl}hept-5-enoic acid ([¹²⁵I]HS-145) was prepared from IS-145 through an organotin intermediate and [¹²⁵I]sodium iodide with high specific radioactivity and good recovery of radioactivity. [¹²⁵I](5Z)-7-{3-endo-[(4-hydroxy 3-iodo-benzensulfonamido)-bicyclo[2.2.1]-heptyl}hept-5-enoic acid ([¹²⁵I]HS-145) was prepared by direct iodination with sodium iodide using a modified chloramine-T method. Both [¹²⁵]HS-145 and [¹²⁵I]HS-145 were found to be valuable radioligands for studying thromboxane A₂ (TXA₂) receptor.