A process for the preparation of unsaturated estradiol-17-ethers.

摘要

Novel steroids of the formula FORM:1072828/C2/1 (wherein R is H or C1- 10 alkanoyl; X is C1- 3 alkoxy and Y is H, or X and Y together are a bond; A and B are H, C1- 5 alkyl, C5 or C6 cycloalkyl, C7- 9 aralkyl or phenyl, or A and B together are a C3 or C4 divalent hydrocarbon chain) are prepared by reacting an estradiol 3-ester with a deriv ative with a lower aliphatic alcohol of an aldehyde or ketone of the formula A.CO.CH2B and, if desired, hydrolysing the ester group. At temperatures below 70 DEG C. compounds wherein X s alkoxy and Y is H are formed, but at above 70-80 DEG C. the compounds wherein X and Y are a bond are obtained. In the latter case an asymmetric carbonyl reagent yields a mixture of products.ALSO:Pharmaceutical compositions for oral or parenteral use as estrogenic agents comprise estradiol derivatives of the formula FORM:1072828/A5-A6/1 (wherein R is H or C1-10 alkanoyl; X is C1-3 alkoxy and Y is H, or X and Y together are a bond; A and B are H, C1-5 alkyl, C5 or C6 cycloalkyl, C7-9 aralkyl or phenyl, or A and B together are a C3 or C4 divalent hydrocarbon chain) and carriers. They may also contain other steroids having androgenic, anabolic or progestational activity, such as 3-cyclopentyloxy-D 3,5-pregnadien-20-one or the 17 a -acetoxy derivative thereof, 3-cyclopentyloxy-17 a -ethynyl-19-nor-D 3,5-androstadien-17 b -ol acetate, 6a -methyl-17a -acetoxy-progesterone or the 6-chloro-6-dehydro derivative thereof, 17a -ethynyl-19- nor-testosterone or its 17-acetate or 17a -ethynyl-19-nor- D 5(10)-androsten-17b -ol-3-one 17-acetate or the corresponding 3b -acetoxy compound. They may also contain buffers or alkalis to prevent hydrolysis of the 17-ethers.