Patent GB-969083-A (GB)
Title: Novel polyhydro-phenanthrene derivatives and a process for the manufacture thereof
IPC: C07C62/32
Filed: 1962-05-14
Abstract: The invention comprises compounds of the formula: <FORM:0969083/C1/1> R2 is hydrogen, C1-7 alkyl, ethynyl or ethenyl and A wherein R1 is hydrogen or C1-7 alkyl; R2 is hydrogen, C1-7 alkyl, ethynyl or ethenyl and A is one of the following groups: <FORM:0969083/C1/2> <FORM:0969083/C1/3> <FORM:0969083/C1/4> <FORM:0969083/C1/5> and their preparation by oxidizing a ketone of the formula: <FORM:0969083/C1/6> to the corresponding acid, esterifying this and reducing the ester with a mixed metal hydride to give a product wherein R1 and R2 are both hydrogen, or by reducing the ketone II with a mixed metal hydride, catalytically activated hydrogen or aluminium isopropoxide to give a product wherein only R1 is hydrogen, or by reacting the ketone II with an alkyl Grignard reagent to give a product wherein R1 and R2 are the same or different alkyl groups, or by reacting the ketone II with an alkali metal acetylide to give a product wherein R1 is alkyl and R2 is ethynyl and then, if desired, reducing the ethynyl group to an ethenyl or ethyl group (any 7-oxo group being protected if desired when organo metallic reagents are being used); and then, if desired, converting the "A" group therein into an "A" group characterized by a higher number by reaction with lithium in liquid ammonia and hydrolysis of the reaction product (A1-->A2), by reduction with lithium in liquid ammonia (A2-->A3) and/or by reduction with a mixed metal hydride or with aluminium isopropoxide (A3-->A4) or by appropriate sequential combination of these reactions. In particular, the keto group of a 2-alkanoyl -7- methoxy-1, 2, 3, 4, 4a, 9, 10, 10a-octa hydrophenanthrene may be acetalized, the product reduced with lithium and an alcohol in liquid ammonia and the reduction product hydrolysed, the hydrolysis product reduced with lithium in liquid ammonia if the tetra deca hydro product is required, the 7-oxo group in the resulting compounds protected by pyrrolidine enamine formation, and the protected compound reduced by one of the processes of the invention for the formation of the C(OH)R1R2 group. Other variants of the process of the invention are also described, some intermediates having 4b-8 and 6-7 double bonds in the "A" ring, and others having a saturated "A" ring, and detailed examples of a number of these are provided. 2-Alkanoyl -7- methoxy-1, 2, 3, 4, 9, 10-hexahydrophenanthrenes are prepared by reacting 1-ethenyl -6- methoxy-3, 4-dihydronaphthalene with alkyl ethenyl ketones to give 2-alkanoyl -7-methoxy-1, 2, 3, 9, 10, 10a-hexahydrophenanthrenes and then isomerizing these. They may be reduced, after acetal formation, to the corresponding octahydro compounds.  The phenanthrene derivatives of the invention, which are stated to be useful as hypocholesterolenic or antifertility agents, antiandrogens, estrogens or anabolic agents, may be made up into pharmaceutical compositions with suitable carriers. They may take the form of tablets, dragees, suppositories, capsules, solutions, suspensions or emulsions and may contain preserving, stabilizing, wetting or emulsifying agents, salts for varying the osmotic pressure or buffers.  Specifications 667,552 and 825,907 are referred to.