GB865915A - Lactones of the steroid series and a process for their manufacture - Google Patents

Abstract

The invention comprises a , b -unsaturated lactones of the steroid series containing at the 17-position a group of the formula: <FORM:0865915/IV (b)/1> wherein R represents a hydroxyl, alkyl, aryl, aralkyl, hydroxyalkyl or carboxyalkyl group (the alkyl radicals in any of the R substituents may be straight or branched chain and may contain further substituents such as halogen atoms and hydroxyl groups), and the preparation there of by 21-esterifying a steroid of the C21 series which carries a 20-keto group and a 21-hydroxy group with an acid of the general formula HOOC-CH2-CO-R1 wherein R1 represents a hydroxy, alkyl, aryl, aralkyl, hydroxyalkyl or acyloxy substituted alkyl group, and treating the resulting 21-ester with a basic condensing agent e.g. a metal alcoholate, hydroxide or oxide such as an alkali metal compound. The steroid reactants used in the above process may be of the pregnane, allopregnane, 4-pregnene, 5-pregnene or 1, 4-pregnadiene series and, apart from the normal substituents in the 3, 11 and 17-positions, may contain hydroxy groups in the 5-and/or 14-positions. Further hydroxy or amino groups in the steroid nucleus are esterified or amidated respectively during the above process and may be subsequently hydrolysed without opening the lactone ring. The acid reactants in the above process may be acetoacetic, malonic, oxalacetic, butyryl acetic or benzoylacetic acid or acetone dicarboxylic acid. The acid reactants may be used in the form of a functional derivative e.g. an amide, acid chloride, acid anhydride, ester or azide. In the examples the following compounds are prepared by the above method: - D 4-andresten-3-one-D a , b -(a -acetyl)-17-butenolide and the corresponding a -benzoyl and a -butyryl compounds; D 5-androsten-3-ol-, ondreston-3-one-, D 4-andrestene-3, 11-dione-17a -ol, and D 1,4-ondrostadiene-3-, 11-dione-17a -ol-D a , b -(a -acetyl)-17-butenolide; the intermediate 21-esters prepared are D 4-pregnene-3, 20-dione-21-ol 21-acetoacetate, butyrylacetate and benzoylacetate; D 5-pregnene-3, 21-diol-20-one, D 1,4-pregnadiene 3, 11, 20-trione-17a , 21-diol, pregnane-3, 20-dione-21-ol and D 4-pregnene-3, 11, 20-trione-17a , 21-diol 21-acetoacetates; D 4-pregnene-3, 20-dione-21-ol 21-ethyl malonate; D 4-pregnene-3, 20-dione-21-ol 21-ethyl a , a 1-acetone-dicarboxylate; and pregnane-3, 20-dione-21 ol-21-acetoxyacetoacetate. g -Acetoxy-acetoacetic acid ester is prepared by reacting g -bromaceto-acetic acid ester with potassium acetate.