Patent GB-936345-A (GB)
Title: New oxido-steroids and process for their manufacture
IPC: C07J75/00
Filed: 1959-10-12
Abstract: The invention comprises saturated or unsaturated pregnanes and androstanes of the partial general formula <FORM:0936345/IV(a)/1> and their preparation by treating a corresponding 11b ,18-dihydroxy steroid or an O-monoacyl derivative thereof with an agent capable of splitting off water or an acid.  They are preferably D 4-3-ketones containing in the 17-position a hydrogen atom or an alkyl group and a free or esterified hydroxyl group, or an oxo group or an alpha hydrogen atom or hydroxyl group and a pregnane side chaim COCH2R2 (wherein R2 is a hydrogen atom or a free or esterified hydroxyl group) but they may alternatively or additionally contain saturated A and B rings, or D 1-, D 5-, D 6-, D 7-, D 14-, or D 16-double bonds, other oxygen substitutents in the 3-, 17-, 20- and 21-positions, or halogen atoms.  Agents which may be used in the process of the invention include lower aliphatic carboxylic acids, bases such as alkali salts of carbonic acid (used when the starting material is an 18-acylate), and halides of phosphorus acids or sulphuric acid or sulphonic acids used in the presence of tertiary amines. Hydroxyl groups in the products may be esterified and/or acetalized oxo groups hydrolysed.  In examples (1) the (18-->11)-lactone of D 53-3,3:20,20-bis-ethylenedioxy-11b , 21-dihydroxy-pregnene-18-acid is reduced with lithium alanate to give D 5-3,3:20,20-bis-ethylenedioxy- 11b ,18, 21-trihydroxy-pregnene, this is acetylated with acetic anhydride to give a partially acetylated product and this is heated with acetic acid to give, on chromatographic separation, dl-D 4-3,20-dioxo-11b ,18-oxido- 21-acetoxy-pregnene and the corresponding 21-ol which may be converted to the acetate in the usual way; (2) the (18-->11)-lactone of D 5-3,3:20, 20-bis-ethylenedioxy- 11b -hydroxy-pregnene-18-acid is reduced with lithium aluminium hydride to give D 5-3,3:20,20-bis-ethylenedioxy-11b ,18-dihydroxy-pregnene and this is heated with acetic acid to give dl-D 4-3,20-dioxo-11b ,18, oxido-pregnene; (3) the bis-ethylenedioxy intermediate of (2) is acetylated to the 18-acetate, this is heated with acetic acid to give D 4-3,20-dioxo-11b -hydroxy- 18-acetoxy-pregnene and this is allowed to stand with potassium bicarbonate solution in methanol to give the product of (2); (4) D 5-3, 3-ethylenedioxy-11b -hydroxy- 17-oxo-18-acetoxy-androstene is reduced with sodium borohydride to give D 5-3,3-ethylenedioxy- 11b , 18-dihydroxy-17b -acetoxy-androstene and D 5-3,3-ethylenedioxy- 11b , 17b -dihydroxy- 18-acetoxy-androstene, and the last named product is treated in boiling acetone with Carboraffin to give dl-D 5-3,3-ethylenedioxy- 11b , 18-oxido- 17b -acetoxy-androstene which on hydrolysis gives dl-D 4-3-oxo-11b ,18-oxido- 17b -acetoxy-androstene and thence, on saponification, the 17b -ol; and (5) the first named of the intermediate products of (4) is treated with p-toluenesulphonyl chloride and pyridine to give the first product of (4); 3,3-ethylenedioxy- 11b ,18-dihydroxy- 17b -acetoxy-androstane (prepared by reduction of the corresponding D 5-compound) similarly gives 3,3-ethylenedioxy-11b ,18-oxido- 17b -acetoxy-and-rostane. Similarly are prepared dl-D 4-3,17-dioxo-11b ,18-oxido-androstene; dl-D 4-3-oxo11b , 18-oxido- 17b -hydroxy-17a -methyl-androstene and dl-D 4-3,20-dioxo-11b ,18-oxido-17a -hydroxy-pregnene.  The above described preparations of starting materials are also referred to in more general terms, and an extensive list of esterifying acids is also provided.  The steroids of the invention may be made up into pharmaceutical compositions, e.g. oily or aqueous solutions contained in ampoules, suspensions, emulsions, implants, tablets, dragees, salves and creams, with suitable carriers.  They may contain preserving, stabilizing, wetting or emulsifying agents, salts for regulating the osmotic pressure or buffers.  The pregnane compounds are stated to exert on mineral metabolism an action similar to that of the known adrenal hormones, and the androstanes are stated to have an anabolic action.