Patent GB-912900-A (GB)
Title: Pregnane-3ª-,16ª--diol-20-ones
IPC: C07J75/00
Filed: 1958-12-22
Abstract: The invention comprises steroids of the formula <FORM:0912900/IV (b)/1> wherein X is hydrogen or fluoro, Y is two hydrogen atoms, a hydrogen atom and a hydroxyl group or an oxo group, and R1 and R2 are hydrogen atoms, acyl radicals of carboxylic or sulphonic acids or ether radicals containing up to 18 carbon atoms, and the corresponding D 9(11)-steroids, at least one of X and Y being different from hydrogen in ring-saturated compounds of the 5a -configuration in which R1 and R2 are hydrogen atoms or acyl radicals and in ring saturated compounds of the 5b -configuration in which at least one of R1 and R2 is an acyl radical; and the preparation of these and of steroids of the above formula which are ring-saturated 5a -pregnanes in which X and Y are hydrogen and one of R1 and R2 is an acyl radical and the other a hydrogen atom by (1) oxidation of the corresponding 20-ols; or (2) treatment of a corresponding 16 - unsubstituted-D 16-pregnene or a ketal thereof with an araliphatic alcohol to form a 16a -O-ether of the 16,17-saturated pregnane, if necessary liberating the 20-keto group and, if desired, converting the ether to the 16a -ol; or (3) microbiologically hydroxylating a corresponding 16-unsubstituted-pregnane; or (4) splitting a corresponding 16a ,17a -epoxide; or (5) reducing a corresponding D 4-or D 5-pregnene or a ketal thereof and, if necessary, liberating the free keto group; or (6) if desired, converting a product of (1) to (5) to an ester or ether of the above general formula.  For microbiological hydroxylation (3) organisms of the genus Streptomyces or of the species Didymella vodakii or Pestalotia funera may be used. Process (4) may be performed either in one stage, using chromyl chloride or acetate, or in 3 stages wherein the epoxide is reacted with an aryl hydrazine to give a D 17(20)-16a -hydroxy-20-arylazo-pregnene, this is reduced to yield the 16a -hydroxy-20-arylhydrazone and the 20-oxo group is then liberated by hydrolysis.  In examples (1) 16a ,17a  - epoxy - allopregnan-3b -ol-20-one and benzoyl chloride give 16a ,17a -epoxy-allopregnan-3b -ol-20-one 3-benzoate and this with chromous acetate in acetic acid gives allopregnane-3b ,16a -diol-20-one 3-benzoate; (2) 16a , 17a  - epoxy - allopregnan - 3b  - ol-20-one 3-trimethylacetate (from the 3-ol and the acid chloride) is treated as in (1) to give allopregnane-3b ,16a -diol-20-one 3-trimethylacetate; (3) allopregnane-3b ,16a -diol-11,20-dione is similarly prepared; (4) D 5-pregnene-3b ,16a -diol20-one is catalytically hydrogenated to give pregnane-3b ,16a -diol-20-one and a allopregnane3b ,16a -diol-20-one; (5) D 4-pregnene-3b ,16a -diol-20-one (prepared by converting 16a -hydroxy-progesterone to the 20-monoketal, reducing the 3-oxo-group and cleaving the ketal) is treated as in (4) to give the same products; (6) allopregnane-3b ,16a -diol-20-one 3-acetate is prepared by the method of (1); (7) pregnane-3b ,16a -diol-20-one is prepared by hydroxylation of pregnan-3b -ol-20-one; (8) the product of (3) is prepared similarly; (9) allopregnane-3b ,11b ,16a -triol-20-one is prepared similarly; (10) D 9(11)-allopregnene-3b ,16a -diol-20 - one is prepared by microbiological hydroxylation of D 9(11)-allopregnen-3b -ol-20-one 3-acetate; (11) D 9(11)-allopregnen-3b -ol-20-one is converted to the bromohydrin, HBr is split off to give 9b ,11b -epoxy-allopregnan-3b -ol-20-one, this is reacted with HF to give 9a -fluoro-allopregnane-3b ,11b -diol-20-one and this is hydroxylated to the 3b ,11b ,16a -triol; (12) D 16-allopregnen-3b -ol-20-one and diphenylcarbinol give 16a  - diphenyl - methoxy - allopregnan-3b -ol-20-one, the p-methoxy-benzyl ether is prepared similarly and the same ethers of allopregnan - 3b ,16a  - diol-11,20-dione are similarly prepared; and (13) sarsapogenin is degraded to D 16-pregnen-3b -ol-20-one 3-acetate, this is epoxylated and hydrolysed to 16a ,17a -epoxy-pregnan-3b -ol-20-one and this by the method of (1) gives pregnane-3b ,16a -diol-20-one.  Reference is also made to the formation of esters and ethers by standard procedures, and to the hydrolysis of esters and ketals.  An extensive list of esterifying and etherifying agents is provided.  The steroids of the invention, which are stated to be capable of causing the elimination of sodium and to be useful in cases of oedema and circulatory disturbances, can be made up into pharmaceutical compositions, such as solutions, suspensions, emulsions, tablets, dragees, ointments and creams.  They may contain preservatives, stabilizers, wetting or emulsifying agents, salts for varying the osmotic pressure or buffers.  Specifications 867,547 and 892,742 are referred to.