Patent GB-1019576-A (GB)
Title: Synthesis of steroids
IPC: C07J9/00
Filed: 1962-07-31
Abstract: The invention comprises a D 7-, D 7 9(11') or D 8-steriod of the general formula <FORM:1019576/C2/1> whereid Y represents oxo or x-or b -hydroxy or acyloxy, X represents oxo, acyloxy, hydroxy or hydrogen and Z represents hydroxy or acyloxy, X being oxo or hydrogen when Y is oxo, and when Y is hydroxy or acyloxy, X is acyloxy or hydrogen and the preparation thereof by treata steroid of the formula <FORM:1019576/C2/2> wherein X and Y have the above significance and B represents hydrogen or lower alkyl, with lithium aluminium hydride, treating the result ing corresponding D 7,20(22),23 - lanostatriene D 8,20(22)23, - lanostatriene or D 7,9(11),20(22)23, lano-statetraene with ozone, and reducing the result ing ozonide with zinc dust and glacial acetic acid and, if desired, forming an ester and/or oxi dizing a 3-hydroxy group and optionally a 16-hydroxy group to form a 3-keto or 3,16-diketo compound.  Pharmaceutical compositions useful in the treatment of Addison's disease contain steroids of the first general formula above and a suitable pharmaceutical carrier. Steroids of the first general formula above, wherein X and Y have the significance indicated and Z represents hydrogen, are prepared by treating compounds of said general formula, wherein Y represents keto or acyloxy and Z represents hydroxy, with an organo-sulphonyl chloride to form the corresponding 21-organo-sulphonate ester, treating these compounds with an alkali metal iodide to form the corresponding 21-iodo compounds, and reducing these com pounds, for example with sodium bisulphite. If a product containing a 3b -hydroxy or acyloxy group is formed, it can be oxidized to the corresponding 3-keto compound after saponi fication of any 3-ester group.  Steroids of the second general formula above wherein B, X and Y have the above significance, are prepared by treating the corresponding steroids having at ring D the formula <FORM:1019576/C2/3> wherein the symbols R may be the same or different and are hydrogen or alkyl and the symbols R1 may be the same or different and are hydrogen or hydroxy, such as eburicoic, poly-porenic, tumulosic, pinicolic, elemolic, elemonic, dehydroeburicoic, dehydroelemonic and de hydroelemolic acids (if necessary after acylating any 3-hydroxy group) with ozone and reducing the resulting ozonide to form the corresponding 24 - keto - 21 - carboxylic - compound, for ex ample, of the formula <FORM:1019576/C2/4> wherein R11 represents an acetyl group (which may also be obtained by treating said steroids having the ring D formula with a hydroxylating agent such as osmium tetroxide and then cleaving the glycol, for example of the formula <FORM:1019576/C2/5> wherein R11 represents an acetyl group), lactonizing the above 24-keto-21-carboxylic-lano stane compounds to form a mixture of steroid a - and b -lactones, for example of the general formulae <FORM:1019576/C2/6> wherein R11 has the previous significance, and dehydrogenating these compounds, for ex ample by treatment with palladium on charcoal. A resulting 3-ester may be saponified to 3-hydroxy and then oxidized to 3-keto.