Patent GB-970446-A (GB)
Title: Improvements in or relating to steroid lactones,hydroxy acids and alkali metal salts thereof
IPC: C07J73/00
Filed: 1962-11-26
Abstract: The invention comprises compounds of the formula <FORM:0970446/C1/1> (wherein R is hydrogen or methyl, Z is ethylene or alkyl substituted ethylene, the alkyl substituents being on the carbon atom adjacent to the oxygen atom, or, when R is methyl, is alkyl substituted methylene, the alkyl substituents being in the a - or b -configuration and containing less than 9 carbon atoms, X is carbonyl, b -hydroxymethylene, a -alkyl-b -hydroxymethylene, b -alkanoyloxymethylene or a -alkyl-b -alkanoyloxymethylene, the alkyl groups containing less than 9 carbon atoms and the alkanoyl groups less than 7 carbon atoms, and the dotted lines indicate an optional double bond from the 5 carbon atom) and the corresponding hydroxyacids and alkali metal salts thereof.  When Z is alkyl substituted methylene, they may be prepared by reacting a steroid of the formula <FORM:0970446/C1/2> (wherein X is carbonyl, b -hydroxymethylene or a -alkyl-b -hydroxymethylene) with a mixture of osmium tetroxide and lead tetraacetate or a similar reagent to give a compound of the formula <FORM:0970446/C1/3> and reacting this with the appropriate alkyl organometallic reagent, to give a mixture of the 1a - and 1b -alkyl isomers, which are separable by virtue of the difference in case of lactonization of the corresponding hydroxy acids.  When Z is an ethylene group and the A ring is saturated, the compounds of the invention may be prepared by reacting a steroid of the formula <FORM:0970446/C1/4> (wherein X is b -hydroxymethylene or a -alkyl-b -hydroxymethylene) with isopropenyl acetate to give the corresponding 3-enol acetate, treating this with ozone, then with zinc dust and then with sodium hydroxide to give the intermediate 17-oxygenated-2-oxo-2,3-seco-3-oic acid, reducing this to the corresponding 2-hydroxy-3-oic acid and cyclizing this by heating in a solvent.  When Z is an ethylene group and R a methyl group and a 4a double bond is present, the compounds may be prepared by reacting a steroid of the formula <FORM:0970446/C1/5> with an oxidizing agent such as lead tetraacetate or periodic acid to give the corresponding 2-oxo-2,3-seco-androst-4-en-3-oic acid, reducing this to the corresponding 2-hydroxy-3-oic acid and refluxing this in an inert solvent; and when Z is an ethylene group and R a hydrogen atom and a 4a double bond is present, the compounds may be prepared by hydrogenating a steroid of the formula <FORM:0970446/C1/6> to give the corresponding ring A saturated steroid, reacting this with a peracid to give the corresponding 6b -hydroxy-3-oxo-A-homo-5a -estran 4-one, converting this to the methane sulphonate and heating this in pyridine.  When Z is an alkyl substituted ethylene radical, the compounds of the invention are prepared by treating a steroid of the formula <FORM:0970446/C1/7> with a peracid.  The lactones may be converted to the corresponding hydroxy acids by heating with aqueous alkali and then acidifying.  Reduction of the 4,5-dehydro lactones results in the corresponding 5a  and 5b  compounds while isomerization with aqueous alkali in methanol followed by acidification gives the 5,6-dehydro lactones.  The 17b -hydroxy compounds may be acylated or oxidized to 17-ones-by conventional procedures.  The lactones of the invention are in equilibrium with the corresponding hydroxy acids in aqueous solution, and the intermediate aldehydo acids are in equilibrium with the corresponding lactonols.  Examples are given.