Patent GB-1012794-A (GB)
Title: New steroids and methods of producing same
IPC: C07J75/00
Filed: 1962-05-11
Abstract: The invention comprises steroids of the general formula <FORM:1012794/C2/1> wherein R3 represents a 3-keto-D 4-system, a D 3,5-enol ether system or a D 3,5-enol ester system, R6 represents a hydrogen, fluorine or chlorine atom in the a ,b  or planar position, Rb represents a double bond between carbon atoms 6 and 7 when R3 is a 3-keto-D 4-system and nb represents 0 or 1, R17 represents a b -hydroxy group or an etherified or esterified b -hydroxy group and R117 represents an alkenyl group bonded in the a -position containing from 3 to 6 carbon atoms, and the preparation thereof by reacting a corresponding 17-keto compound, or such compound containing a protected 3-keto group, with an alkenyl or alkynyl magnesium halide or alkali metal alkynyl compound containing from 3 to 6 carbon atoms and hydrolysing the initial reaction product and, when an alkynyl magnesium halide or alkali metal alkynyl compound is used, hydrogenating the resulting 17b -hydroxy-17a -alkynyl-steroid to form the 17a -alkenyl radical, or by reacting a corresponding 17-keto compound, or such compound containing a 3-protected keto group, with an alkali metal acetylide containing from 2 to 5 carbon atoms having a free hydrogen atom attached to a triply-bound carbon atom, hydrolysing the resulting reaction product, reacting with an alkali metal to replace the aforesaid free hydrogen atom by an alkali metal, reacting the product with an alkyl halide containing from 1 to 4 carbon atoms such that the resulting group attached to the 17-position contains from 3 to 6 carbon atoms and hydrogenating the product to convert the triple bond into a double bond, or by reacting a corresponding 17-keto compound or such compound containing a protected 3-keto group with a lithium alkenyl containing from 3 to 8 carbon atoms in which the lithium atom is bound to a saturated carbon atom.  Any of the above processes may be modified in that before or after introducing the 17a -alkenyl group the 6-position of the steroid nucleus is substituted by a chlorine or fluorine atom by reacting the required steroid containing a 3-keto-D 4-system with N-chloro-succinimide or other N-chloro-imide or by reacting the required steroid containing a 3-enol ether or 3-enol ester D 3,5-system with perchloryl fluoride, an N - chloro - imide or chlorine or by epoxidizing a 3-keto-D 4,6-system and treating the resulting 3-keto-D 4-6,7-epoxide system with hydrogen chloride or hydrogen fluoride, or a 6-double bond is introduced by dehydrogenating the required steroid containing a 3-keto-D 4-system with chloranil or by dehydrohalogenatin the required 3-keto-D 4-6-halo-steroid with an organic or inorganic base, or by oxidizing the required 3-hydroxy-D 3,5-steroid according to the Oppenauer method in the presence of a quinone.  The 3-keto group may be protected in the above processes by conversion to a 3-anamine, 3-enolether, 3-enolester or 3-ketol group, for example, by reaction with a secondary amine such as pyrrolidine or piperidine, or an aliphatic diol.  The 17b -hydroxy group in the product of any of the above processes may be acylated for example, with a mono- or di-carboxylic acid or an anhydride or acid halide thereof, or may be etherified with an organo-halide.  Ester groups derived from carboxylic acids may be further substituted by one or more halogen atoms, amino groups or sulphonic acid groups.  The 3-keto-D 4-system may also be formed by acid and/or alkaline hydrolysing a D 3 5-3-enolester or a D 3,5-3-enolether system, by reducing a 3-keto-D 4,6-system either by catalytic hydrogenation or by means of an alkali metal and liquid ammonia, if desired, followed by acid or alkaline isomerisation of the intermediately formed 3-keto-D 5-system, by oxidizing a 3-hydroxy-D 4- or 3-hydroxy-D 5-system by the Oppenhauer method, by means of manganese dioxide or by the action of 2,3-dichloro-5,6-dicyano-benzoquinone, or by halogenating a 3-keto-ring A saturated system at C4 and dehydrohalogenatin the resulting 3-keto-4-halo-system.  Pharmaceutical compositions which may be in the form of tablets, pills, powders, and injectable solutions contain as the active ingredient a steroid of the above general formula.  Specification 912,200 is referred to.