Astatobenzoic acids

Astatobenzoic acid isomers have also been prepared by heterogeneous isotopic exchange by using the corresponding iodobenzoic acid. Halogen exchange has been effected under molten conditions, or with the substrate dissolved in a molten inert high-dielectric solvent, such as acetamide yields of 60-70% have been obtained (35). 

Synthesis of the astatophenyl oxazoiine, 4-astatobenzoic acid and the antiestrogen 3-astatotamoxifen... 

Norseyev and coworkers32 obtained similar results when preparing the three isomers of astatobenzoic acid from the corresponding Cl, Br or 1 analogues using essentially the same... 

TABLE 4. Yields of astatobenzoic acid isomers prepared by heterogeneous halogen exchange from chloro-, bromo- and iodobenzoic acids (t = 200 °C)32... 

All other investigations in this field were directed towards conjugating astatine with proteins. In most cases / -astatobenzoic acid (PAtBA) is produced first via diazotization PAtBA is subsequently bound to the NH2 group of protein by means of acylation with mixed anhydrides42 14. 

Electrophilic demetalation of thallium trifiuoroacetate derivatives was utilized by Visser and Diemer60 to synthesize o-astatobenzoic acid and /7-astatoanisole. The organometallic compounds are formed by reaction of benzoic acid and of anisole with thallium trifiuoroacetate at room temperature, in the dark. Astatination was carried out in dilute H2S04, in the presence of KI within 30 minutes. Yields of70-90% were obtained the astati-nated products were separated by extraction and identified by TLC or—in the case of o-astatobenzoic acid—on the basis of its pKa value determined by extraction with heptane. 

A somewhat simpler procedure was followed to prepare 3-astatotamoxifen (24) since in this case the acid and base treatment is not needed. Isolation and identification of astati-nated products—together with their iodinated carriers—are performed by HPLC or TLC. The HPLC radiochromatogram of 24 and the chromatogram of its inactive iodo analogue can be seen in Figure 3. In the presence of iodine, radiochemical yields of 80% and 60% could be achieved for / -astatobenzoic acid and astatotamoxifen, respectively. Without using an iodinated carrier, however, the yield did not exceed 0.5-1%. 

Milius and coworkers61 have found that the C—At bond of / -astatobenzoic acid is stable in hot acidic and basic solutions as well as in the presence of moderate reducing or oxidizing agents. 

In mitochondrial research the phosphate-transporting protein from rat liver mitochondria has been labeled with ° Hg-mersalyl At For protein labeling with astatine (alpha emitter) the following procedures may be u reaction of the protein with p-astatobenzoic acid < ndensation reaction with peptide bond and protein acetylation While labeling by the above procedures seems to be sufficiently stable a remarkable instability of the At-label was obserwd when astatinated protein was prepared electrophoretically 202) jjjg results of these authors indicate that the tyrosine-astatine bond is unstable. The conclusion of Vau an et al. that astatinated proteins lore as much as 50% of their biological activity and, in addition, are extremely toxic, is very serious. 

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