Patent GB-929278-A (GB)
Title: Steroids and their production
IPC: A61K31/57
Filed: 1959-04-12
Abstract: <FORM:0929278/IV(a)/1> The invention comprises 10a -methyl-9b -steroids of the general formulae J and M shown in the Figure, wherein QVI represents a methyl group and QVII represents an aldehyde group or an aldehyde addition group such as a cyanhydrin or bisulphite addition group, or an O-acyl group, or QVI represents hydrogen and QVII represents a -COOR group in which R represents a lower aliphatic hydrocarbon group having from 1 to 6 carbon atoms, and X has the formula shown in the Figure in which R1 represents a hydrogen atom or a methyl group, R2 represents none or one or more double bonds at one or more of the positions 1, 2, 3, 4, 5, 6 and 15, R3 represents a hydrogen atom or a methyl, ethyl, hydroxy, etherified hydroxy or esterified hydroxy group, R4 represents a keto, hydroxy, etherified hydroxy or esterified hydroxy group, R5 represents a hydrogen or halogen atom, R6 represents a hydrogen or halogen atom or a methyl, hydroxy, etherified hydroxy or esterified hydroxy group, R7 represents a hydrogen or halogen atom, R8 represents hydrogen or a hydroxy or keto group, and R11 represents a hydrogen atom or a hydroxy, etherified hydroxy or esterified hydroxy group; the preparation of the compounds of formula J wherein QVI represents a methyl group and QVII represents an aldehyde group by dehydrobrominating 10a -methyl-9b -steroids of the general formula G shown in the Figure wherein X has the above significance; the preparation of the compounds of the formula J, wherein QVI represents a methyl group and QVII represents an O-acyl group, by acylating a 10a -methyl-9b -steroid of the general formula E shown in the Figure, wherein X has the above significance, with an isopropenyl acylate to form a 10a -methyl-9b -steroid of the general formula H shown in the Figure, wherein X has the above significance, and catalytically shifting the double bond, for example, with p-toluenesulphonic acid (in this method, an enolizable system in ring A such as a 3-keto-D 1-, 3-keto-D 4- or 3-keto-D 4,6-system may be converted back to the required system by iodinating the enolisation product with iodosuccinimide in a solvent such as dioxon, and then deiodinating with sodium bisulphite); the preparation of the compounds of the formula J, wherein QVI represents hydrogen and QVII represents the group -COOR, by condensing a 10a -methyl-9b -steroid of the general formula E shown in the Figure, wherein X has the above significance, with a dialkyl oxalate in the presence of an alkali metal alkoxide or equivalent condensing agent to form a 10a -methyl-9b -steroid of the general formula R shown in the Figure, wherein X and R have the above significance and M represents a metal atom brominating this compound to form a dibromo-reaction product and decomposing the dibromo-reaction product in an alkali medium such as an alkali metal alkanoate; and a method for the preparation of the compounds of the formula M by treating compounds of the formula J, wherein QVI represents a methyl group and QVII represents an aldehyde group, with a per-acid such as mono-perphthalic, peracetic and perbenzoic acids. At any stage of the processes referred to above it is possible to introduce a D 1-double bond by dehydrogenation with iodine pentoxide, iodic acid, selenic acid or selenium dioxide, or by biochemical dehydrogenation, or by dehydrohalogenation; to introduce at the 2-position an alkyl, halo, ester, hydroxy or ether substituent by reaction of a 3-ketone with an oxalic ester followed by either alkylation with an alkyl halide to form a 2-alkyl substituent or halogenation to form a 2-halo substituent which may then be converted to a 2-ester group, then hydrolysed to a 2-hydroxy group and finally etherified to a 2-ether group; to introduce a D 6-double bond by allylic halogenation of a D 4-compound followed by dehydrohalogenation; to oxidise a 3-hydroxy group to a 3-keto group; or to esterify a 3-hydroxy group. n the examples the following compounds are prepared: 3-keto-lumibis-nor-chol-4,17(20)-diene-22-ol and the corresponding 4,6,17(20)-triene-22-ol compound, the cyanhydrin addition products of these compounds, and the 17,20-epoxy compounds corresponding to these compounds.  Specifications 929,272, 929,276, 929,277 and 929,279 also are referred to.