11BETA-ALKYL STEROIDS OF THE ESTRANE SERIES

摘要

1495531 3 - Unsubstituted - 11 - alkylestrane compounds AKZO NV 10 Dec 1974 [19 Dec 1973] 53306/74 Heading C2U Novel steroids of the estrane series having the formula wherein R 1 and R 2 are each C 1-4 alkyl but not t-butyl, R 3 is =O or (α-X)(#-Y) in which X is H or alkyl, alkenyl, alkynyl, alkadienyl, alkadiynyl or alkenynyl of at most 4 carbon atoms and Y is a free, esterified or etherified hydroxyl group, and there is a #5-, #5(10)- or A4-double bond present are prepared from steroids of the formula wherein there is a #9(11) or #11 double bond or an external double bond from the 11-position, X is (R 5 )(R 6 ) in the latter case and (H)(R 5 )(R 6 ) in the former, in which R 5 and R 6 are each H or C 1-3 alkyl and together contain at most 3 C atoms and either ring A is aromatic and contains a free, esterified or etherified hydroxy group at the 3-position or it is of the same structure as in the products, i.e. contains a #4- or #5(10)-double bond or is saturated and accompanied by a #5-double bond, but optionally also contains in the 3-position a free or protected oxo group, a free, esterified or etherified hydroxy group, a halogen atom or a hydrocarbon sulphonyloxy group. These steroids are catalytically hydrogenated; the aromatic A ring, if present, is reductively converted to a ring containing a 3-oxo-#4 or 3-oxo-#5(10) grouping using Birch reduction and hydrolysis of the #2,5(10)-3-enolate formed; a 3-oxo-#4 grouping, if desired, is converted via the 3-enol acylate and a reduction of the #3-double and a hydrolysis of the 3-acyloxy group to a 3- hydroxy-#5 grouping; and any group present or still present at position-3 is removed by known methods, e.g. a 3-keto group is removed via a 3-ethylene dithio ketal, and a 3#-hydroxy group via a 3#-chloro compound. Groups in the 17-position may be introduced and interconverted by standard procedures; in one such procedure an intermediate is 11#,18-dimethyl- 17α- 31 - (111 - ethoxy - ethoxy) - prop - 11- ynyl - #4 - estren - 17# - ol, and, in another, intermediates are 11# - methyl - 17α- acetyl- #4 - estren - 17# - ol and its 17# - trimethylsilyl ether, and- 11# - methyl - 17α- isopropenyl- #4 - estren - 17# - ol 17# - trimethylsilyl ether. The novel steroids have various steroid hormonal properties and they may be made up into pharmaceutical compositions with suitable carriers. Specification 1,455,270 is referred to.