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. ln particular, the preparation of 16-alpha-<Sup>123</Sup>I-17-beta-estradiol and 16-beta- <Sup>123</Sup>I-17-beta-estradiol are shown and are synthesized from a 17-beta-estradiol-16-beta-triflate. Both 16-alpha-<Sup>123</Sup>I-and 16- beta-<Sup>123</Sup>I-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 <Sup>123</Sup>I 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.