Patent GB-1046243-A (GB)
Title: Steroid compounds and the preparation thereof
Inventor: BARTON DEREK HAROLD RICHARD
IPC: C07J1/00
Filed: 1961-12-05
Abstract: The invention comprises 19-hydroxy-cholesterol and a process for the preparation of 19-hydroxy-steroids in which a 6b -hydroxy-steroid having the structure <FORM:1046243/C2/1> wherein R represents an acyloxy group or a protected keto group such as a ketal or thioketal group, and X represents a substituent b -eliminatable with a 4-hydrogen atom such as a halogen atom, a hydroxyl group or a hydrocarbon substituted sulphonyloxy group, is reacted with an oxidizing agent capable of removing hydrogen from a hydroxyl group to yield the corresponding 6b ,19-ether which is subjected to hydrolysis and, if required, oxidation to convert the group R to a keto oxygen function, b -elimination of the substituent X with a 4-hydrogen atom being effected simultaneously or subsequently to yield an unsaturated 6b ,19-ether which is then reduced with a reducing system selected from the group consisting of dissolving metal and low valency metal ion reducing systems (which is defined as a reducing agent comprising a metal dissolving in water or an acidic aqueous medium to liberate hydrogen or a compound containing metal ions in a lower valency state capable of being oxidized to a higher valency state such as a titanous, chromous or stannous salt) whereby the ether bond to the 6b -position is reductively cleaved to form a 19-hydroxy-steroid. In particular, the 6b -hydroxy-steroid of the above structure may first be converted as above to a 6b ,19-ether having the partial structure <FORM:1046243/C2/2> wherein R and X have the above significance, which is then subjected to hydrolysis and, if required, oxidation to convert the group R to a keto group, b -elimination of the substituent X being effected simultaneously or subsequently to form a 6b , 19-ether having the partial structure <FORM:1046243/C2/3> and this ether is reduced as above to form a 3 - oxo - 4,5 - dehydro - 19 - hydroxy - steroid. The initial oxidation in the above processes may be carried out with lead tetra-acetate or with a reagent system generating positive chlorine, bromine or iodine ions, for example, heavy metal oxides, such as mercuric, silver or plumbic oxide, in the presence of iodine, or acylates of lead or metals of the 1st and 2nd sub-groups of the Periodic Table, such as silver or mercury acetate or lead tetra-acetate, and iodine, or cyanogen chloride, bromide or iodide, iodine monochloride or iodine monobromide. A particular preferred starting compound is a 5a -halo-3b -acyloxy-6b -hydroxy-androstan-17-one (if a 5a -chloro-6b -hydroxy-steroid is used as a starting compound, the above processes may be modified in that a corresponding 5a -bromo-6b -hydroxy-steroid is treated with a base to yield a 5,6b -oxide which is then reacted with hydrogen chloride).  The starting compound may be further substituted at the 11- and/or 17-position by a keto group, at the 16-position by a methyl group, at the 9-position by a halogen atom, or at the 17-position by a hydroxy, acetyl or 1,5-dimethylhexyl group.  When the substituent at the 5-position to be eliminated with a 4-hydrogen atom is a halogen atom or a sulphonyloxy group, the elimination may be carried out with acid catalyst, when the substituent at the 5-position is a hydroxy group, the elimination may be effected with a dehydrating agent such as phosphorus oxychloride or by heating. Pharmaceutical compositions contain as the active ingredient 19-hydroxy-cholesterol (blood cholesterol lowering effect), 19-hydroxy-testosterone or its 17-acetate (exert an anabolic action), or 19-hydroxy-progesterone or 19-hydroxy - 17a  - acetoxy - progesterone (progestational action).