Patent GB-808904-A (GB)
Title: 17 -a-hydroxy-steroids
IPC: C07J71/00
Filed: 1955-02-16
Abstract: The invention comprises D 4-11b ,17a ,21-trihydroxy - 3,18,20 - trioxopregnene, its cyclosemiacetal and its 18,21-dibenzoate, and their preparation by cleaving between carbon atoms 4 and 5 a saturated or unsaturated polyhydrochrysene of general formula: <FORM:0808904/IV (b)/1> (wherein R1 and R3 represent free or functionally converted hydroxyl or oxo groups, R4 is a free or functionally converted aldehyde group or a radical convertible thereinto, R5 is a methyl or a free or functionally converted oxygenated methyl group, which compounds have a double bond in the 4:5 position or a free or enolized oxo group in the 5 position); and subjecting the resulting compound to ring-closure to form a cyclopentanophenanthrene derivation, if necessary, forming an oxo group and/or a double bond in ring A; while at any stage an oxo or hydroxyl group may be protected, any functionally converted oxo or hydroxyl group set free and a free or converted hydroxyl group introduced into the 17-position, and any double bond in ring D hydrogenated.  The cleavage between carbon atoms 4 and 5 may be achieved by ozonolysis, hydroxylation with OsO4(or by H2O2 or a per acid and hydrolysis of the resulting 4,5-epoxide) followed by splitting of the glycol with lead tetraacetate or periodic acid; compounds containing a 5-oxo group are initially reduced, e.g. with sodium borohydride, and the 5-hydroxyl group eliminated to give the 4:5 double bond; alternatively, 4-methyl-5-oxo compounds are nitrosated, when cleavage occurs giving a free or esterified carboxyl group and an oximino group.  Ring closure is preferably achieved with a condensing agent, e.g. an alkali metal alcoholate, amide or hydride if the reactive group at position 1 of the phenanthrene is carbalkoxy, or piperidine acetate or benzoate if the group is an aldehyde.  In examples: (1) the benzoate of the cyclosemiacetal of dl - D 4,8(14) - 1b  - hydroxy - 4 - formyl - 10 - ethylenedioxy - 17 - formyl - 13 - methylpoly-hydrochrysene is reduced with methanolic sodium borohydride and re-benzoylated giving the dibenzoate of the cyclosemiacetal of the corresponding 4 - hydroxymethyl compound, which is oxidized with osmium tetroxide, the product cleaved with periodic acid giving the dibenzoate of the cyclosemiacetal of 4bb -methyl - 1b  - formylmethyl - 2b  - formyl - 2a -(31 - hydroxy - 21 - oxo - propyl) - 7 - ethylenedioxy - 1,2,3,4,4aa ,4b,5,6,7,8,10,10ab - dodecahydrophenanthrene - 4b  - ol, which is then cyclized in benzene containing acetic acid and piperidine to the 18,21-dibenzoate of the 11b ,18-cyclosemiacetal of dl- D 5,16-11b ,21-dihydroxy - 18,20 - dioxo - 3 - ethylenedioxypregnandiene; this compound is treated with alkaline H2O2, rebenzoylated, and the resulting dibenzoate of the 11b ,18-cyclosemiacetal of dl - D 5 - 11b ,21 - dihydroxy - 16a ,17a  - oxido-18,20 - dioxo - 3 - ethyllenedioxypregnene reacted with HBr in acetic acid and then with Raney nickel in ethanol giving the 18,21-dibenzoate of the 11b ,18-cyclosemiacetal of dl-D 4 - 11b ,17a ,21 - trihydroxy - 3,18,20 - trioxopregnene which is then saponified to the free triol; (2) the lactone of dl-D 4,8(14)-1b -hydroxy-4 - formyl - 10 - ethylenedioxy - 17 - carboxy - 13 - methyl - polyhydrochrysene treated as in (1) yields the corresponding 17a ,21-dihydroxy-20-oxo-pregnene compound; (3) the benzoate of the lactone of dl-D 4,8(14)-1b -hydroxy-4-hydroxymethyl - 10 - ethylenedioxy - 17 -carboxy - 13 - methylpolyhydrochrysene is reduced with LiAlH4 and benzoylated to the dibenzoate of the cyclosemiacetal of dl - D 4,8(14) - 1b -hydroxy - 4 - hydroxymethyl - 10 - ethylenedioxy - 17 - formyl - 13 - methylpolyhydrochrysene which is ozonized at -30 DEG  C. and the product after decomposition of the ozonide is cyclized as in (1) to the 18,21-dibenzoate of the 11b ,18 - cyclosemiacetal of dl - D 5,16 - 11b ,21-dihydroxy - 18,20 - dioxo - 3 - ethylenedioxypregnadiene; (4) the acetate of the cyclosemiacetal of dl-D 4,9(14)-1b -hydroxy-4-formyl-10 - keto - 13 - methyl - 17 - formylpolyhydrochrysene is reduced with NaBH4, re-acetylated and the resulting diacetate of the cyclosemiacetal of dl-D 4,9(14)-1b -hydroxy-4-hydroxynethyl - 10 - keto - 13 - methyl - 17 - formyl - polyhydrochrysene converted to the 10-ethylene ketal and then as in (1) to the corresponding 17a ,21-dihydroxy-20-oxo-pregnene compound.