Patent GB-929275-A (GB)
Title: Steroids and their production
IPC: A61K31/57
Filed: 1959-04-09
Abstract: The invention comprises 10a -methyl-9a -steroids of the general formula VI shown in the Figure, wherein R2 represents no double bonds or one or more double bonds at one or more positions 1, 3, 4, 5 and 6, R4 represents a keto, hydroxy, esterified hydroxy or etherified hydroxy group, QVI represents a methyl group and QVII represents an aldehyde group or a cyanhydrin or bisulphite addition product thereof, or an O-acyl <FORM:0929275/IV(a)/1> group, or QVI represents hydrogen and QVII represents a -COOR group, 'acyl' is derived from an aliphatic carboxylic acid having from 1 to 6 carbon atoms and R represents an alkyl group having from 1 to 6 carbon atoms; the preparation thereof, wherein QVI represents a methyl group and QVII represents an aldehyde group, by dehydrobrominating 10a -methyl-9a -steroids of the general formula IIIA in the Figure wherein R2 and R4 have the above significance, for example, by reacting with a basic metal oxide or hydroxide or with a primary, secondary or tertiary amine; the preparation thereof, wherein QVI represents a methyl group and QVII represents an O-acyl group, by reacting 10a -methyl-9a -steroids of the general formula V shown in the Figure with the isopropenyl ester of acetic acid or other aliphatic carboxylic acid having from 1 to 6 carbon atoms to produce 10a -methyl-9a -steroids of the general formula VA shown in the Figure, and treating these compounds with p-toluenesulphonic acid or other catalyst effective to move the double bond from the 20(21)-position to the 17(20)-position (in this process a 3-keto-D 4-grouping may be converted to a D 3,5-3-enol-acylate grouping which will necessitate iodinating the reaction product with iodosuccinimide in dioxan and then deiodinating with sodium bisulphite to reform the 3-keto-D 4-grouping); and the preparation thereof, wherein QVI represents hydrogen and QVII represents a -COOR group, R having the above significance, by reacting 10a -methyl-9a -steroids of the general formula V, wherein R2 and R4 have the above significance, with a dialkyl oxalate in the presence of an alkali metal alkoxide as condensing agent, to form 10a -methyl-9a -steroids of the general formula VB shown in the Figure, brominating these compounds and decomposing the dibrominated products with an alkali metal enolate (in this process a 3-keto-D 4-grouping may be converted to a D 3,5-3-enol-acylate grouping which will necessitate iodinating the reaction product with iodosuccinimide in dioxan and then deiodinating with sodium bisulphite to reform the 3-keto-D 4-grouping); and the preparation thereof, wherein QVI represents hydrogen and QVII represents a -COOR group, R having the above significance, by reacting 10a -methyl-9a -steroids of the general formula V, wherein R2 and R4 have the above significance, with a dialkyl oxalate in the presence of an alkali metal alkoxide as condensing agent to form 10a -methyl-9a -steroids of the general formula VB shown in the Figure, brominating these compounds and decomposing the dibrominated products with an alkali metal enolate (in this process the dialkyl oxalate may associate at the 2 and/or 4 positions of a 3-keto-compound unsubstituted at the 2 and/or 4 positions so that 2- and/or 4-bromo substitution takes place during the step of brominating and the process may require an additional step of removing the bromine atoms by reduction with zinc dust and glacial acetic acid).  The first process above may be modified in that the 10a -methyl-9a -steroid reactants of the general formula IIIA in the Figure are prepared by a process described in Specification 929,274.  The substituent at the 3-position of the 10a -methyl-9a -steroids of the general formula VI in the Figure may be varied, for example, a hydroxy group may be oxidised to keto-manganese dioxide being a suitable oxidising agent, or a hydroxy group may be esterified.  In the examples the 10a -methyl-9a -steroids of the formulae XXI and XXII shown in the Figure are prepared.  Specifications 929,271 and 929,273 also are referred to.