Conjugation hormones, effects

The first step of the Robinson annulation is simply a Michael reaction. An enamine or an enolate ion from a jS-keto ester or /3-diketone effects a conjugate addition to an a-,/3-unsaturated ketone, yielding a 1,5-diketone. But as we saw in Section 23.6,1,5-diketones undergo intramolecular aldol condensation to yield cyclohexenones when treated with base. Thus, the final product contains a six-membered ring, and an annulation has been accomplished. An example occurs during the commercial synthesis of the steroid hormone estrone (figure 23.9). 

PNP-DTP has been used to photoaffinity label the thyroid hormone nuclear receptors in intact cells by preparing a derivative of 3,5,3 -triiodo-L-thyronine with the crosslinker (Pascual et al., 1982 Casanova et al., 1984). Effective photoreactive conjugation was found to occur after irradiation with UV light at 254 or 310 nm. 

Thyroid hormones exert their effect by binding to nuclear receptors in target organs. Both the thyroid hormones are well absorbed after oral administration. They are conjugated with sulfuric acid in liver and excreted in bile. 

In some studies, women taking estradiol or conjugated estrogens for hormone replacement therapy had no cholestasis or hepatotoxicity, as assessed by rises in serum alkaline phosphatase, bilirubin, or transaminases, whereas these effects did occur with ethinylestradiol. 

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