Patent GB-805603-A (GB)
Title: Oxygenated steroids and process of making same
IPC: C07J71/00
Filed: 1955-01-14
Abstract: The invention comprises steroid compounds of the formula <FORM:0805603/IV (b)/1> and their derivatives saturated in the 16:17 position (R is a hydrogen atom, a methyl group or a hydroxymethyl group) and esters, ethers, ketals and acetals of these compounds, and a process for their preparation by intramolecular condensation of compounds of the formula <FORM:0805603/IV (b)/2> (R is as above defined) or the corresponding 3-ketals, preferably in the presence of a basic condensing agent, and, if required, subsequently hydrogenating the 16:17 double bond of the resulting steroid. Specified condensing agents are alkali metal alcoholates or amides, triethylamine, piperidine, quaternary ammonium bases, and salts of strong organic bases with carboxylic acids, e.g. acetic or benzoic. Specified derivatives of the resulting steroids include esters, thioesters, enol esters, ethers, enol ethers, thioethers, acetals, ketals, lactones, mercaptals, cyclosemiacetals, thiol- and thion-esters, enamines, hydrazones and semicarbazones.  In examples: (1) (2 --> 4b )-lactone of 1b -formylmethyl - 2a  - acetonyl - 2b  - carboxy - 4bb  - methyl - 7 - ethylenedioxy - 1,2,3,4,4aa ,4b,5,6,7, 8,10,10ab  - dodecahydrophenanthrene - 4b  - ol in t-butanol and benzene containing a quaternary base is slowly distilled under nitrogen, the residual solution diluted with ether, washed with NaH2PO4, Na2CO3 solutions, evaporated and the residue in benzene chromatographed on alumina, giving the (18 --> 11b )-lactone of d,l - D 5,16 - 3 - ethylenedioxy - 11b  - hydroxy - 20 - oxo - pregnadiene 18-acid, which is hydrogenated over palladium-on-strontium carbonate to the (18 --> 11b )-lactone of d,l- D 5-3-ethylenedioxy - 11b  - hydroxy - 20 - oxo - pregnene-18-acid; subsequent treatment with p-toluene sulphonic acid in acetone gives the corresponding D 4-3-keto compound; likewise the (2 --> 4b )-lactone of 1b -formylmethyl-2a -(o  - acetoxy - acetonyl) - 2b  - carboxy - 4bb  - methyl - 7 - ethylenedioxy - 1,2,3,4,4aa ,4b,5,6,7, 8,10,10ab  - dodecahydrophenanthrene - 4b  - ol yields the (18 --> 11b )-lactone of d,l- D 5,16-20-oxo - 3 - ethylenedioxy - 11b  - hydroxy - 21 - acetoxy - pregnadiene - 18 - acid, the corresponding D 5-pregnene and finally the D 4-3-keto derivative; acid hydrolysis of the D 5,16-21-acetoxy compound gives the (18 --> 11b )-lactone of d,l - D 4,16 - 3,20 - dioxo - 11b ,21 - dihydroxypregnadiene - 18 - acid, which is re-esterified to the 21-acetate; (2) the lactone of 1b ,2a -di-(formylmethyl) - 2b  - carboxy - 4bb  - methyl - 7 - ethylenedioxy - 1,2,3,4,4aa ,4b,5,6,7,8,10,10ab -dodecahydrophenanthrene - 4b  - ol is cyclized with piperidine in benzene and acetic acid to the (18 --> 11b )-lactone of d,l - D 5,16 - 3 - ethylenedioxy - 11b  - hydroxy - 17 - formyl - androstadiene-18-acid, which is hydrogenated over palladium-calcium carbonate to the D 5-compound, hydrolysed with HCl in acetone to the lactone of d,l- D 4-3-oxo-11b -hydroxy-17-formylandrostene-18-acid, oxidized with sodium dichromate in acetic acid and methylated with diazomethane to the (18 --> 11b )-lactone of d,l-D 4 - 3 - keto - 11b - hydroxy - etienic acid methyl ester 18-acid. In a "Preparation" aldosterone monoacetate is oxidized with chromium trioxide to the (18 --> 11b )-lactone of D 4 - 3,20 - dioxo - 11b  - hydroxy - 21 - acetoxy - pregnene-18-acid and hydrolysed with methanolic potassium bicarbonate to the corresponding 11b -21-diol.  Specifications 805,606 and 805,609 are referred to.