Clark H. Cummins

Radiolabeled steroidal estrogens in cancer research

It has now been more than 30 years since the laboratory verification of the localization of estrogen in certain animal tissues. Much has been learned since that time regarding the details of this process, including the presence of specific receptors for these hormones in target tissues, the mechanism of ligand binding, the association of the ligand-receptor complex with unique chromatin sequences, and the activation of transcription. A concrete use of this knowledge has been the exploitation of these receptors as a targeting mechanisms for radiopharmaceuticals. This is an exciting area that encompasses both diagnosis and therapy. This review will summarize the in vitro and in vivo data obtained from evaluation of the many compounds that have been examined as radiolabeled receptor ligands, and will also discuss the chemistry necessary for their preparation. In particular, relative binding affinity values for relevant compounds will be tabulated, grouped according to molecular class. For those materials for which biodistributions have been performed, uterine (target), liver (nontarget, clearance), and, when available, tumor tissue uptake values are presented. These data should provide a reminder of what has been accomplished, and should serve as a working reference for those engaged in the pursuit of new candidates for these applications.

Synthesis of symmetrical diarylalkynes by double Stille coupling of bis(tributylstannyl)acetylene

Abstract Treatment of bis(tributylstannyl)acetylene with two equivalents of an aryl iodide in the presence of tetrakis(triphenylphosphine)palladium (0) affords good yields of the symmetrical diarylalkyne. This approach provides a convenient and safe alternative to the use of acetylene in the preparation of these compounds.

Cis-Trans stereoselectivity in the Stannylmetallation of Diphenylacetylene

Stereospecific cis- or trans- stannylcupration of diphenylacetylene can be obtained by temperature control during vinylcuprate hydrolysis.

Synthesis and radiochemistry of 2,4-disubstituted 17α-iodovinylestradiols

This report details the preparation of three compounds which are structurally designed to have depressed metabolism and/or conjugation: 2,4-dibromo-, 2,4-dichloro-, and 2,4-dimethyl-17α-iodovinylestradiol. Their synthesis includes the use of two novel transformations based upon tin chemistry: preparation of an intermediate 17α-vinulstannanes via stannylcupration of a 17α-ethynyl steroid, and preparation of the 2,4-dimethyl functionality via a palladium catalyzed coupling of 2,4-dibromoestrone acetate with tetramethyltin. The preparative radiochemistry of these three materials is also described.

Stereospecific Syntheses of Clomiphene and Tamoxifen via Stannylcupration of Diphenylacetylene

Abstract Stereospecific trans-stannylcupration of diphenylacetylene affords a 1,2-dimetallostilbene which may be elaborated into either Clomiphene or Tamoxifen through palladium-catalyzed coupling with an aryl iodide.

Preparation of steroidal vinylstannanes by stannylcupration of ethynylestradiols

Abstract Hydrostannylation of 2,4-dibromo-17α-ethynylestradiol results in both vinylstannane formation and reductive dehalogenation of the A-ring bromides. An alternative approach based upon alkyne stannylcupration was developed, and compared with hydrostannylation on a series of four A-ring substituted ethynylestradiols.