Patent GB-850735-A (GB)
Title: Steroid compounds
Filed: 1956-12-13
Abstract: The invention comprises compounds of the general formula : <FORM:0850735/IV(b)/1> wherein Ac represents an acyl radical, R DEG represents hydrogen or an alkyl radical, T DEG  is a ketal or thioketal group, X is hydrogen or a fluorine atom, Y is a hydrogen atom, a hydroxy group or a keto group, and Z DEG  is a hydrogen atom or a hydroxy group, and the preparation thereof by treating the corresponding compound free from substituents at the 2-position with an alkyl ester of a mono- or di-carboxylic acid in the presence of a base to form a 2-acyl-compound of the above general formula wherein R DEG  represents hydrogen, and, when required, alkylating the 2-acyl-compound to form a 2-acyl-2-alkyl compound of the above general formula.  The above process may be modified in that the reactant free from substituents at the 2-position is prepared by converting the 20-keto group of a compound of the general formula : <FORM:0850735/IV(b)/2> wherein X, Y and Z DEG  have the above significance, into a 20-ketal or 20-thioketal group, e.g. an alkylenedioxy group such as an ethylene ketal or propylene ketal group.  The alkylation may be carried out in an organic solvent such as methanol or acetone, in the presence of a basic material such as an alkali metal carbonate, using an alkyl iodide such as methyl iodide as the alkylating agent.  The base used in the reaction with the alkyl ester is preferably a strong base such as an alkali metal alkoxide.  Suitable alkyl esters are methyl formate, methyl acetate and dimethyl oxalate.  The 20-ketal group may be prepared by reacting the 3, 20-diketo reactant with an excess of alkylene glycol under anhydrous conditions in the presence of an acidic catalyst to produce the corresponding 3,20-bis(alkylenedioxy) compound and then selectively hydrolysing this compound with 90% aqueous acetic acid to convert the 3-alkylenedioxy group to a 3-keto group.  In the examples the following compounds are prepared :-2 - formyl - 20 - ethylenedioxy - 4 - pregnene - 17a ,21 - diol - 3,11 - dione (this compound exists largely in the enolic form, i.e. the 2-hydroxymethylene form), 2-methyl-2-formyl - 20 - ethylenedioxy - 4 - pregnene - 17a 21 - diol-3,11-dione, 2-methyloxalyl-20-ethylenedioxy-4-pregnene-17a ,21-diol-3,11-dione, 2-propyl-2-methyloxyalyl - 20 - ethylenedioxy - 4 - pregnene - 17a ,21-diol-3,11-dione, 20-ethylenedioxy-4-pregnene-11b ,17a ,21-triol-3-one (from the corresponding 3,20-bis(ethylenedioxy) compound), 2-methyloxalyl - 20 - ethylenedioxy - 4 - pregnene - 11b ,17a ,21-triol-3-one, 2-methyl-2-methyloxalyl-20 - ethylenedioxy - 4 - pregnene - 11b ,17a ,21 - triol-3-one and the corresponding 2-ethyl substituted compound, 3,20-bis(ethylenedioxy)-9a -fluoro-5-pregnene-11b ,17a ,21-triol and the corresponding 11-one compound, 20-ethylenedioxy-9a -fluoro-4-pregnene-11b ,17a ,21-triol-3-one and the corresponding 11-one compound, 2-methyloxalyl - 20 - ethylenedioxy - 9a  - fluor - 4 - pregnene-11b ,17a ,21-triol-3-one and the corresponding 11-one compound, 2-methyl-2-methyloxalyl-9a  - fluoro - 20 - ethylenedioxy - 4 - pregnene - 11b ,17a ,21-triol-3-one and the corresponding 11-one compound, and 2-hexyl-2-methyloxalyl-9a  - fluoro - 20 - ethylenedioxy - 4 - pregnene - 11b ,17a ,21-triol-3-one. Corresponding 11-unsubstituted and 21-unsubstituted compounds are also obtainable by the methods of the examples.