Jean Bowler

Reduction of Prostaglandin Enone Intermediates with Aluminium Isopropoxide

Abstract Because of their enormous therapeutic potential in several, diverse, disease areas the natural prostaglandins and their analogues have been the synthetic target of a large amount of chemical effort in recent years1. A crucial step in many of the successful syntheses is the reduction of an α, β-unsaturated ketone to a mixture of allylic alcohols. For example in Coreys synthesis2 of the natural compounds the enone (Ia) is reduced to the enols (IIa) and (IIIa). This is best achieved using bulky borohydride reducing agents3 with the additional advantage that a preponderance of the required isomer (IIa) is obtained. However, in our experience use of the more convenient sodium or zinc borohydrides is often complicated by the fact that 1,4-reduction occurs to give the saturated ketone and sometimes saturated alcohols.

Structural derivatives of tamoxifen and oestradiol 3-methyl ether as potential alkylating antioestrogens

Abstract The oestrogenic and antioestrogenic activity of potential alkylating derivatives of tamoxifen and oestradiol 3-methyl ether have been compared with tamoxifen and oestradiol benzoate in the immature rat. Although all the tamoxifen derivatives demonstrated an ability to inhibit the binding of [ 3 H] oestradiol to rabbit or rat uterine oestrogen receptors in vitro , none of the compounds was as potent as tamoxifen in tests for antioestrogenic activity in vivo . The potential alkylating derivatives of oestradiol 3 -methyl ether were not antioestrogenic. The properties of all the compounds in vivo did not suggest irreversible effects upon the uterus. Since the assays in vitro did not predict activity in vivo the results indicate that only agents with very high affinity for the oestrogen receptor that do not potentially require metabolic activation may be useful in vivo .