GB909201A - New steroid products and process of preparing them - Google Patents

Abstract

The invention comprises steroid lactones of the general formula <FORM:0909201/IV (b)/1> wherein Y represents hydrogen or methyl (there either is or is not a 2:3 double bond in the lactone ring), X represents keto, b -hydroxy and a -hydrogen, or b -acyloxy and a -hydrogen where the acyl radical is derived from an aliphatic acid containing from 1 to 9 carbon atoms, and wherein when X represents keto there is either a 4:5 double bond or a 5a -hydrogen atom, and when X is b -hydroxy (or acyloxy) and a -hydrogen there is either a 5:6-double bond or a 5a -hydrogen atom but not 2:3-double bond in the lactone ring, the salts produced by treating the above lactones with alkali, and the corresponding hydroxy-acids derived from the salts; and processes for the preparation of (a) the lactone of 4-hydroxy4 - (3b -hydroxy-5-androsten-17b -yl)-2-pentenoic acid or the corresponding butenoic acid by hydrogenating the corresponding 2-pentinoic or butinoic acid with one mol of hydrogen in the presence of Lindlar palladium in tetrahydrofuran or alcohol solution, (b) the lactone of 4-hydroxy-4-(3b -hydroxy-5-androsten-17b -yl) pentanoic acid or of 4-hydroxy-4-(3b -hydroxy-5a -androstane-17b -yl) pentanoic acid or of either of the corresponding butanoic acids by hydrogenating 4-hydroxy-4-(3b -hydroxy-5-androsten-17b -yl) pentinoic acid or the corresponding butanoic acid in the presence of 10% palladium over carbon in tetrahydrofuran or alcohol solution until the requisite amount of hydrogen is absorbed, (c) the 3-acyloxy compounds defined by the general formula above by acylating the corresponding 3-hydroxy compounds, e.g. to form 3-acetates, propionates, valerates, b -phenylpropionates, b -cyclopentylpropionates and hemisuccinates and (d) the 3-keto compounds defined by the general formula above by oxidising the corresponding 3b -hydroxy compound having the double bond, if at all, in the 5:6 position. Therapeutic compositions useful as nutriuretics contain a steroid lactone of the above general formula and a solid and/or liquid pharmaceutically acceptable carrier. p 4-Hydroxy - 4 - (3b -hydroxy-5-androsten-17b -yl)-T-pentionic and -butinoic acids are prepared by reacting ethynyl magnesium bromide with pregn-5-en-3b -ol-20-one and 17b -formyl-5-androsten-3b -ol-3-acetate to form 20-ethynyl-21-nov-5-pregnene-3b ,20-diol respectively, and reacting the 20-ethynyl compounds with a Grignard reagent and then carboxylating with carbon dioxide.