Patent GB-764323-A (GB)
Title: Preparation of steroid compounds
IPC: C07J75/00
Filed: 1952-11-28
Abstract: The invention comprises D 22-3-acetoxy-11-hydroxy - ergostene, D 22 - 3,11 - dihydroxy - ergostene, D 22 - 3,11 - diketo - ergostene and a process for the preparation of a cyclopentanoperhydrophenanthrene compound having at rings B and C the formula <FORM:0764323/IV(b)/1> wherein R represents a hydroxy or keto radical by reducing with a metal and a liquid medium which reacts with the metal to form hydrogen (liquids which react violently with the metal are excluded, e.g. water must not be used with sodium or potassium) a D 8(9)-cyclopentanopolyhydrophenanthrene compound having at rings B and C the structure <FORM:0764323/IV(b)/2> When R represents a hydroxy radical, the resulting compound can be oxidized to an 11-keto - cyclopentanoperhydrophenanthrene compound, e.g. with chromic acid-preferably using acetone or glacial acetic acid as the liquid medium for the oxidation reaction.  Suitable metallic reducing agents for the above reduction are alkali metals such as sodium, potassium or lithium, a mercury amalgam of an alkali metal, an alkaline-earth metal such as calcium, and zinc.  The 11-keto-cyclopentanoperhydrophenanthrene compounds are obtained from D 8(9)-11 keto reactants when the reduction is effected with an alkali metal in a medium consisting of a lower alkanol such as methanol, ethanol, propanol, isopropanol, butanol or amyl alcohol, or liquid ammonia.  The lower alkanol can be used in admixture with liquid ammonia to form 11-hydroxy - cyclopentanoperhydrophenanthrene compounds.  The lower alkanol may also be used with an inert solvent, e.g. a hydrocarbon solvent such as benzene, toluene or petroleum ether, or an ether solvent such as diethyl ether.  Liquid ammonia can be used admixed with ether.  It is preferred to use a liquid medium comprising a lower alkanol with a concentrated aqueous solution of a mineral acid such as concentrated hydrochloric acid when zinc is used as the metallic reducing agent.  Mercury amalgam can also be used in a liquid medium comprising a lower alkanol or admixed with a hydrocarbon solvent and/or ether.  The above reduction process may be modified in that the D 8(9) - cyclopentanopolyhydrophenanthrene reactant is prepared by the action of boron trifluoride on a monoepoxide of a D 7,9(11)-cyclopentanopolyhydrophenanthrene compound which may be prepared by the process claimed in Specification 764,321. The preferred D 8(9)-11-keto reactants are those having a sterol side chain attached to the carbon atom in the 17-position of the molecule such as D 8(9),22-11-keto - ergostadiene, D 8(9),22 - 3 - acyloxy - 11 - keto - ergostadiene, e.g. D 8(9),22 - 3 - acetoxy - 11 - keto - ergostadiene, D 8(9) - 3 - acyloxy - 11 - keto - cholestene, e.g. D 8(9) - 3 - acetoxy - 11 - keto - cholestene, D 8(9) - 3 - hydroxy - 11 - keto - cholestene, D 8(9)22 - 3 - acyloxy - 11 - keto - stigmastadiene, e.g. D 8(9),22-3-acetoxy-11-keto-stigmastadiene, D 8(9),22 - 3 - hydroxy - 11 - keto-stigmastadiene, D 8(9) - 3 - acyloxy - 11 - keto - cholenic acid. e.g. D 8(9)-3-acetoxy-11-keto-cholenic acid, D 8(9)-3-hydroxy-11-keto-cholenic acid, D 8(9) - 3 - acyloxy - 11 - keto - bisnorallocholenic acid, e.g. D 8(9)-3-acetoxy-11-keto-bisnorallocholenic acid, D 8(9)-3-hydroxy-11-keto-bisnorallocholenic acid, D 8(9)-3-acyloxy-11,20-diketo - allopregnene, e.g. D 8(9) - 3 - acetoxy - 11,20-diketo-allopregnene, D 8(9)-3-hydroxy-11,20 - diketo - allopregnene, D 8(9) - 11 - keto-dehydrotigogenin acylate, e.g. D 8(9)-11-keto-dehydrotigogenin acetate, and D 8(9)-11-keto-dehydrotigogenin.  In the examples the following compounds are prepared:-D 22-3-hydroxy-11-keto - ergostene, D 22 - 3,11 - dihydroxy - ergostene, D 22-3,11-diketo-ergostene (two isomers believed to be the 11a - and 11b -hydroxy compounds), D 22 - 3 - acetoxy - 11 - keto - ergostene (the 3-acetoxy group may be hydrolysed with alcoholic sodium hydroxide to form a 3-hydroxy group), 11-keto-tigogenin and 11-hydroxy-tigogenin.  The following compounds may also be prepared by the above reduction procedure:-D 22 - 11 - hydroxy - ergostene, D 22 - 11 - keto - ergostene, 3,11 - dihydroxy - cholestane, 3 - hydroxy - 11 - keto - cholestane, D 22-3,11 - dihydroxy - stigmastene, D 22 - 3 - hydroxy - 11 - keto - stigmastene, 3,11 - dihydroxy - cholanic acid, 3 - hydroxy - 11 - keto - cholanic acid, 3,11 - dihydroxy - bisnorallocholanic acid, 3 - hydroxy - 11 - keto - bisnorallocholanic acid, 3,11,20 - trihydroxy - allopregnane and 3 - hydroxy - 11,20 - diketo - allopregnane.  The following compounds may be obtained from the optional additional oxidation step:-D 22-11-keto - ergostene, D 22 - 3,11 - diketo - ergostene, 3,11 - diketo - cholestane, D 22 - 3,11 - diketo - stigmastene, 3,11 - diketo - cholanic acid, 3,11-diketo - bisnorallocholanic acid, 3,11,20 - triketo-allopregnane and 3,11-diketo-tigogenin.