Synthesis of a Tetradentate Oxorhenium(V) Complex Mimic of a Steroidal Estrogen

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We are developing oxometal(V) complexes as high affinity ligands for the estrogen receptor. When labeled with technetium-99m, these complexes might be used as imaging agents for estrogen receptor-positive breast tumors. We describe the synthesis of a tetradentate oxorhenium(V) amino amido thioether thiol (AATT) complex in which the metal complex replaces the CD ring portion of estradiol. This complex is a close steric congener of the steroid and has a similar molecular volume. It was synthesized from norphenylephrine via an efficient Pictet-Spengler cyclization to give a tetrahydroisoquinoline that was then readily elaborated into the tetradentate chelate system. Treatment with an oxorhenium(V) salt led to the formation of the desired complex as a mixture of two diastereomers in modest yield. The relative stereochemistry of these isomers was easily assigned from their NMR spectra. On the basis of their octanol-water partition coefficients, these complexes are considerably more hydrophilic than is estradiol, and their binding affinity for the estrogen receptor is low. The AATT unit in these complexes represents a new chelation system for the oxometal(V) complexes of group 7 transition metals, and compared to other closely related bisbidentate and other tetradentate systems we have studied, these complexes are quite stable. Nevertheless, the low binding affinity of these complexes for the estrogen receptor emphasizes the fact that metal complexes must most likely have an electronic complementarity with good receptor ligands, as well as a size and shape complementarity, in order for them to exhibit high affinity receptor binding.

Original languageEnglish (US)
Pages (from-to)6290-6297
Number of pages8
JournalJournal of Organic Chemistry
Issue number18
StatePublished - 1997

ASJC Scopus subject areas

  • Organic Chemistry


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