Patent GB-753724-A (GB)
Title: Hydroxy ketones of the perhydrochrysene series and their esters
IPC: C07J63/00
Filed: 1954-01-01
Abstract: The invention comprises (a) D-homoetiocholane derivatives of the general formula <FORM:0753724/IV(a)/1> wherein one or two of X,X1 and X11 represent(s) = O and the remaining two or one represent(s) <FORM:0753724/IV(a)/2> where R is hydrogen or an acyl group; (b) the preparation of compounds of the above formula in which X is <FORM:0753724/IV(a)/3> or <FORM:0753724/IV(a)/4> , X1 is O =, <FORM:0753724/IV(a)/5> or <FORM:0753724/IV(a)/6> and X11 is <FORM:0753724/IV(a)/7> by treating a compound of the general formula <FORM:0753724/IV(a)/8> with hydrogen cyanide, catalytically hydrogenating the resulting 17-cyano-17-hydroxy compound to the corresponding 17-aminomethyl-17-hydroxy compound, and treating the latter with nitrous acid; (c) subsequent interconversions of free and esterified hydroxy groups and keto groups in accordance with Examples (3) to (5) below.  The acyl group(s) R may be derived from lower aliphatic mono- and di-carboxylic acids and monocyclic aromatic carboxylic acids, optionally containing one or more inert substituents such as nitro, alkyl, alkoxy or halogen.  In examples: (1) etiocholan-3a -ol-11:17-dione is reacted with potassium cyanide and aqueous acetic acid to produce a mixture of epimeric 17-cyanoetiocholane-3a :17-diol-11-ones which are reduced with hydrogen in acetic acid in the presence of Adams platinum oxide catalyst and the resulting 17-aminomethyletiocholane-3a :17-diol - 11 - one acetate is treated with sodium nitrite and acetic acid to yield D-homoetiocholan - 3a  - ol - 11:17a - dione; (2) 3a  - acetoxyetiocholane-11:17-dione similarly gives 3a -acetoxy - D - homoetiocholane - 11:17a - dione, which is alcoholysed with methanolic caustic potash to the product of (1); (3) 3a -acetoxy-D-homoethiocholane-11:17a-dione is reduced by sodium borohydride in aqueous dioxan to a mixture of 3a -acetoxy-D-homoetiocholan-17aa -and-17ab  - ol - 11 - ones, which are separated by fractional crystallization and each alcoholysed to the corresponding free diolone; (4) 3a -acetoxy - D - homoetiocholan - 17ab  - ol - 11-one is esterified in the 17-position with benzoyl chloride and pyridine, the 3a -acetoxy group is hydrolysed and the resulting hydroxy group oxidized with chromic oxide in acetic acid, and the product is hydrolysed to D-homoetiocholan-17ab  - ol - 3:11 - dione; (5) 3a  - acetoxy - D - homoetiocholane - 11:17a - dione is reacted with b -mercaptoethanol in dioxan in the presence of anhydrous sodium sulphate and zinc chloride to form the 17a-ethylenehemithioketal, the 11-keto group of which is reduced with lithium aluminium hydride and the product refluxed with Raney nickel and acetone to produce D-homoetiocholane-3a :11b -diol-17a-one. Reference is also made to the following conversions: (i) D-homoetiocholan-3a -ol-11:17a-dione to D-homoetiocholane-3:11:17a-trione by oxidation with chromic acid or an N-haloamide; (ii) the product of (i) to D-homoetiocholan-11-ol-3:17a-dione by reduction after protection of the 3- and 17a-keto groups by converting them to ethylenehemithioketal groups; (iii) 17a - benzoyloxy - D - homoetiocholane-3:11 - dione to D - homoetiocholane - 11:17a-diol - 3 - one by ethylenehemithioketalization of the 3-keto group, reduction of the 11-keto group and conversion of the 3- and 17a-substituents to keto and hydroxy respectively; (iv) compounds of the first formula above, wherein X and X1 are = O and X11 is preferably <FORM:0753724/IV(a)/9> to a mixture thereof with the epimeric D-homoandrostanes by halogenation (e.g. bromination) in the 4-position, dehydrohalogenation and hydrogenation of the resulting 4,5-double bond.