HALOGEN LABELED COMPOUNDS INCLUDING ESTRADIOL DERIVATIVES, THEIR SYNTHETIC INTERMEDIATES AND THE SYNTHESES THEREOF

摘要

A method of preparation of halogen labeled organic compounds is described. In particular, estradiol derivatives labeled by halogen substitution at C-16 are synthesized according to the present invention. A triflate intermediate is prepared from which either 16-alpha-halo-substituted-17-beta-estradiols or 16-beta-halo-substituted-17-beta-estradiols can be rapidly formed as desired. In particular, the preparation of 16-alpha-123I-17-beta-estradiol and 16-beta-123I-17-beta-estradiol are shown and are synthesized from a 17-beta-estradiol-16-beta-triflate. Both 16-alpha-123I- and 16-beta-123I-17-beta-estradiol made according to the present invention are shown to have a high specific activity. The method of synthesis is sufficiently rapid so that the relatively short half-life of 123I is readily accommodated. The high stereospecificity of each step of the reaction sequence in preparing the labeled estradiols provides for highly efficient syntheses and little waste of radio-label.