Patent GB-889309-A (GB)
Title: 17-carboxyalkylated 3-oxygenated 6-methyl-androsten-17-ol lactones and intermediates therefor
IPC: C07J75/00
Filed: 1959-12-10
Abstract: The invention comprises compounds of the general formulae <FORM:0889309/IV (b)/1> wherein Z represents an ethylene or vinylene radical, X represents a carbonyl or b -hydroxymethylene radical, and M represents hydrogen or an alkali metal or an ammonium radical, 3b - acetoxy - 17a  - (3 - acetoxypropyl) - 5a , 6a  - epoxy - androstan - 17b  - ol, 3b , 5a , 17b  - tri - hydroxy - 17a  - (3 - hydroxypropyl) - 6b  - methyl - androstane and 17a -(2-carboxyethyl)-5a , 17b -dihydroxy-6b -methyl-androstan-3-one lactone.  The 6b -methyl compounds of the above general formuls may be prepared by reacting an appropriate 17a -carboxy-alkylated androst-5-ene-3b ,17b -diol of the lactonic general formula <FORM:0889309/IV (b)/2> with lithium aluminium hydride to form the corresponding triol, diesterifying the triol (the 17b -hydroxy group being sterically hindered), converting the diester to the corresponding 5,6-epoxy compound with perbenzoic acid, treating the 5,6-epoxy compound to open the epoxy ring and cleaving the ester groups with methyl magnesium bromide to form 6-methyl-3b ,5a ,17b -triol having at the 17a -position the group -Z-CH2OH, wherein Z has the above significance, oxidising this compound with chromic acid to form a carboxyl group which lactonises with the 17b -hydroxyl group, heating this compound with finely-divided magnesium-silica gel in a solvent medium to form a 6b -methyl lactone of the first general formula above, wherein X represents a carbonyl group and the double bond is in the 4(5)-position, and when required, reducing this compound with sodium borohydride to form the corresponding compound wherein X represents the hydroxymethylene radical.  The 6-methyl-5-en-3b -ols of the invention are prepared by treating compounds of the general formula <FORM:0889309/IV (b)/3> wherein m is 0 or 1, with a Grignard reagent and then carbon dioxide to form the corresponding 17a -carboxy-alkynyl compound, and then hydrogenating selectively to produce compounds in which Z represents a vinylene radical or an ethylene radical using as a catalyst palladium on calcium carbonate or palladium on charcoal, respectively, as the hydrogenation catalyst.  The 6a -methyl-3-oxo compounds of the invention having the general formula <FORM:0889309/IV (b)/4> wherein Z has the above significance, are prepared by oxidising according to Oppenauer the corresponding 3b -hydroxy-6b -methyl compounds and, if necessary, reducing the resulting 6a -methyl-3-oxo compounds with sodium borohydride to form 3b -hydroxy-6a -methyl compounds of the general formula <FORM:0889309/IV (b)/5> wherein Z has the above significance.  The latter compounds may be converted to the corresponding 3-keto-6-methyl-5(6)-compounds by oxidising with chromium trioxide in acetone.  The lactones of the first general formula above may be contacted with aqueous alkali to form alkali metal salts of the corresponding hydroxy acids of the second general formula above from which the free acids may be obtained by a brief exposure to a proton source.  Detailed examples are given.  17a  - Alkynyl - 6 - methylandrost - 5 - ene - 3b ,-17b -diols of the general formula <FORM:0889309/IV (b)/6> wherein m is 0 or 1, are prepared by condensing 3b  - hydroxy - 6 - methylandrost - 5 - en - 17 - one with acetylene or propargyl bromide.