Patent GB-777996-A (GB)
Title: Steriod compounds and their preparation
Filed: 1955-03-30
Abstract: The invention comprises 9a -hydroxy-11-oxygenated cyclopentanophenanthrene compounds having at rings B and C the formula <FORM:0777996/IV(b)/1> wherein R represents a keto or hydroxy group and which may be substituted in one or more of the following positions: in the 3-position by a keto, hydroxy or acyloxy group; in the 17-position with an a - or b -hydroxy group; in the 20-position with a keto group and in the 21-position by a hydroxy or acyloxy group, and a process which comprises reacting a 9b ,11b -oxido-cyclopentanophenanthrene compound having the pregnane carbon skeleton with an aqueous strong non-oxidizing mineral acid to produce the corresponding 9a ,11b -dihydroxy-cyclopentanophenanthrene compound, and reacting said compound with an oxidizing agent to form the corresponding 9a -hydroxy-11-keto compound.  The compounds used as reactants in the above process may be fully saturated pregnanes or pregnenes having double bonds in one or more positions such as D 1, D 4, D 5, D 6, D 7 and D 14 double bonds.  Any such double bonds may be intermediarily protected in the above process, for example, by saturation with halogen or hydrogen halide or by conversion into pentacyclic isosteroids.  The pregnanes or pregnenes used in the above process may be in the normal or allo series.  Examples of 9b ,11b -oxide reactants are 9b ,11b  - oxidio - D 4 - pregnene-17a ,21 - diol - 3,20 - dione, 9b ,11b  - oxido - D 4 - pregnene - 21 - ol - 3,20 - dione, 9b ,11b  - oxido - D 4 - pregnene - 21 - ol and the 21-acylates of such compounds such as the acetate, propionate, butyrate, benzoate and phenylacetate, 9b ,11b -oxido - D 4 - pregnene - 17a  - ol - 3,20 - dione, 9b ,11b  - oxido - D 4 - pregnene - 3,20 - dione, 9b ,11b  - oxido - D 4 - pregnene - 3 - one, similar compounds having a 3a - or 3b -hydroxy group and their acylates such as those mentioned above, and the corresponding compounds in the pregnane and allopregnane series and pregnene series having double bonds such as D 1, D 4, D 6 and D 7 double bonds.  The treatment with the non-oxidizing mineral acid may be carried out with hydrochloric, sulphuric, phosphoric or perchloric acid-preferably in an aqueous solvent mixture, suitable solvents being dioxane, tetrahydrofuran, acetone, benzene or diethyl ether.  During the treatment a 21-acyloxy group may be hydrolysed to form a 21-hydroxy group. Products containing 3- and/or 21-hydroxy groups may be acylated in the usual way to form acylates such as those mentioned above.  The oxidizing agents that may be used to oxidize the 11b -hydroxy group are chromium trioxide in glacial acetic acid or an N-halo amide or imide such as N-bromoacetamide in an inert solvent.  If other oxidizable substituents are present in other parts of the molecule, they are preferably deactivated or protected against oxidation, for example, by esterification.  The preferred compounds having at rings B and C the above formula are pregnane-, allopregnane-, a pregneneparticularly D 4-pregnene-9a ,11b -diols and 9a ,11-ones.  Specific compounds mentioned having at rings B and C the above formula wherein R represents a hydroxy group, are D 4 - pregnene - 9a ,11b ,17a ,21 - tetrol - 3,20-dione, D 4 - pregnene - 9a ,11b ,21 - triol - 3,20 - dione, D 4 - pregnene - 9a ,11b ,17a  - triol - 3,20 - dione, D 4 - pregnene - 9a ,11b  - diol - 3,20-dione, D 4 - pregnene - 9a ,11b  - diol - 3 - one, pregnane-9a ,11b ,21 - triol - 3,20 - dione, pregnane - 3a , 9a ,11b ,17a ,21-pentol - 20 - one, pregnane - 9a , 11b ,17a - triol - 3,20 - dione, pregnane - 9a ,11b -diol - 3,20 - dione, pregnane - 3a ,9a ,11b  - triol - 20 - one, pregnane - 9a ,11b  - diol - 3 - one, pregnane - 3a  (and b ), 9a ,11b ,21 - tetrol - 20 - one, pregnane - 3a  (and b ), 9a ,11b ,17a  - tetrol - 20 - one, allopregnane-9a ,11b ,17a ,21 - tetrol - 3,20-dione, allopregnane - 9a ,11b ,21 - triol - 3,20 - dione, allopregnane - 9a ,11b ,17a ,21 - tetrol - 20-one, allopregnane - 9a ,11b ,21 - triol - 20 - one, allopregnane - 9a ,11b ,17a  - triol - 3,20 - dione, allopregnane - 9a ,11b  - diol - 3,20 - dione, and allopregnane - 3a ,9a ,11b ,21 - tetrol - 20 - one.  These and similar compounds may be acylated in the 3- and/or 21-position so as to form mono-and/or di-acylates such as the acetate, propionate, butyrate, benzoate and phenylacetate. Specific compounds mentioned having at rings B and C the above formula, wherein R represents a keto group, are allopregnane- and D 4-pregnene - 9a ,17a ,21 - triol - 3,11,20 - trione - 21 - acetate, pregnane, allopregnane- and D 4-pregnene - 9a ,21 - diol - 3,11,20 - trione - 21 - acetate, allopregnane- and D 4 - pregnene - 9a  - ol - 3,11,20 - trione, allopregnane- and D 4 - pregnene - 9a ,17 - diol - 3,11,20 - trione, pregnane-9a ,21 - diol - 3,11,20 - trione, pregnane - 9a  - ol - 3,11,20 - trione, pregnane- and D 4 - pregnene - 9a  - ol - 3,11 - dione, pregnane - 3a  (and b ), 9a ,21 - triol - 11,20 - dione - 3,21 - diacetate, pregnane - 3a ,9a ,17a  - triol - 11,20 - dione - 3 - propionate, pregnane - 3b ,9a ,17a  - triol - 11,20 - dione - 3 - hemisuccinate, allopregnane - 3a ,9a , 21 - triol - 11,20 - dione - 3,21 - diacetate, and other acylates such as the propionates, butyrates, benzoates and phenylacetates.  In the examples, the following compounds are prepared: D 4 - pregnene - 9a ,11b ,17a ,21 - tetrol - tetrol - 3,20-dione and the 21-acetate thereof, D 4-pregnene-9a ,11b ,21-triol-3,20-dione and the 21-acetate thereof, D 4 - pregnene - 9a ,17a ,21-triol-3,11,20-trione and the 21-acetate thereof, and D 4 - pregnene - 9a ,21 - diol - 3,11,20 - trione and the 21-acetate thereof.  Starting compounds.  9b ,11b -Oxido-D 4-pregnene - 21 - ol - 3,20 - dione - 21 - acetate is prepared by refluxing potassium acetate, 9a -bromo-D 4 - pregnene - 11,21 - diol - 3,20 - dione - 21 - acetate and ethyl alcohol.