Synthesis and radiochemistry of 2,4-disubstituted 17 alpha-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-17 alpha-iodovinylestradiol. Their synthesis includes the use of two novel transformations based upon tin chemistry: preparation of an intermediate 17 alpha-vinylstannanes via stannylcupration of a 17 alpha-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.

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.

A convenient synthesis of bifunctional chelating agents based on diethylenetriaminepentaacetic acid and their coordination chemistry with yttrium(III).

The bifunctional chelating agents N,N,N',N'',N''-pentakis(carboxymethyl)-1- [(4-aminophenyl)methyl]-diethylenetriamine and N,N,N',N'',N''-pentakis(carboxymethyl)-1-[(4-aminophenyl)methyl]-4- methyldiethylenetriamine were prepared in six-step syntheses in overall yields of 38% and 31%, respectively. The use of bromoacetate esters in the synthesis allowed large-scale flash chromatographic purification of reaction products. The synthesis of N,N,N',N'',N''-pentakis(carboxymethyl)-1- [(4-aminophenyl)-methyl]-4-methyldiethylenetriamine resulted in a mixture of two diastereomers. Chelation of yttrium-(III) with these bifunctional chelating agents resulted in 1:1 chelates. In the case of N,N,N',N'',N''-pentakis(carboxymethyl)-1-[4- aminophenyl)methyl]diethylenetriamine, two diastereomers were observed upon chelation, as expected. In the case of N,N,N',N'',N''- pentakis(carboxymethyl)-1-[(4-aminophenyl)-methyl]-4- methyldiethylenetriamine, only three of the four anticipated diastereomers were observed.