title: 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.
abstract: An improved synthetic scheme for (5Z)-7-(3-endo-[(benzenesulfonamido)-bicyclo[2.2.1]heptyl)-h ept-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-iodobenzenesulfonamido)-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-benzenesulfonamido)-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 [125I]HS-145 and [125I]HS-145 were found to be valuable radioligands for studying thromboxane A2 (TXA2) receptor.
authors.affiliation: Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082.
authors.forename: W M
authors.initials: WM
authors.lastname: Kan
authors.forename: H H
authors.initials: HH
authors.lastname: Tai
mesh_terms: D001792:Blood Platelets / Q000648:ultrastructure; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis*; D002462:Cell Membrane / Q000648:ultrastructure; D005229:Fatty Acids, Monounsaturated / Q000138:chemical synthesis*; D006801:Humans; D007457:Iodine Radioisotopes; D011869:Radioligand Assay; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D017482:Receptors, Thromboxane / Q000032:analysis*
chemical_list: D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D007457:Iodine Radioisotopes; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C056566:S 145