Patent GB-587030-A (GB)
Title: Manufacture of lactones of the cyclopentanopolyhydrophenanthrene series
IPC: C07J75/00
Filed: 1942-06-12
Abstract: Lactones of the cyclopentanopolyhydrophenanthrene series are produced by subjecting to the action of an oxidizing agent known to be capable of introducing in the a -position to a double bond a carboxyl group, a compound of this series which contains in the nucleus in the 17-position or in a side chain itself attached in the 17-position a grouping <FORM:0587030/IV/1> where X is a free esterified or amidated carboxyl group.  The Y's are hydrogen or hydrocarbon groups, and n is zero, 1 or 2, and where a carbonyl group has been introduced in the a -position to the double bond the product is subjected to the action of an agent known to be capable of converting a -CO- group into a -CY(OH) group.  If necessary, the product is treated with a lactonising agent, and when it contains a substituted hydroxyl group or esterified or amidated carboxyl group or nitrile group, subjecting to the action of an acid or a base as a hydrolysing agent before the treatment with a lactonising agent.  Oxidizing agents mentioned include selenium dioxide, chromic acid, lead tetra-acylates, halogens or iodoso-compounds.  These agents are usually employed in solution. Parent materials mentioned D  20 : 22 - 3 - acetoxy - nor - cholenic acid methyl ester, D  4 : 5 : 20 : 22-3-keto-21-methylnor-choladienic acid methyl ester, D  5 : 6, 20 : 22-3 - acetoxy - 21 : 22 - dimethyl - nor - choladienic acid ethylester, or corresponding cholenic acid derivatives or -25-homocholenic acid derivatives, D  22 : 23 - 3 - acetoxy - 22 - methyl - 21 - norcholenic acid methyl ester, D  20 : 22-3 : 7 : 12-triacetoxycholenic acid ethyl ester or -nor-cholenic acid ester, also the analogous 3 : 7-or 3 : 12-diacyloxy acid esters, free acids, amides or nitriles.  In examples: (1) an acetic anhydride solution of D  20 : 22-3-acetoxy-norallocholenic acid methyl ester is mixed drop by drop at boiling temperature with an aqueous solution of selenium dioxide.  After the oxidation, the separated selenium is removed and after chromatographic purification there is recovered D 20 : 22-3-acetoxy-21-oxy-norallocholenic acid lactone.  Acid saponification gives the 3 : 21-dioxy compound.  (2) A glacial acetic acid-acetic anhydride solution of D  5 : 6, 20 : 22-3-acetoxy-21-methyl-norcholadienic acid methyl ester is oxidized with lead tetra-acetate to form D  5 : 6, 20 : 22-3-acetoxy - 21 - methyl - 21 - oxy - nor - choladienic acid lactone.  Homologous and substituted parent materials yield corresponding products in a similar manner.  (3) A chloroform solution of D  5 : 6, 25 : 26-3-acetoxy - 26 - methyl - cholesta - diene-26-carboxylic acid is converted into its acid chloride by phosphorus trichloride and then treated with bromine, this saturates the D  5 : 6-double bond and also oxidizes the carbon atom in the g -position to carboxyl, and there can be isolated by chromatographic methods D  5 : 6, 25 : 26 - 3 - acetoxy - 24 - oxy - 26 - methyl - cholestadiene-26-carboxylic acid lactone and also D  5 : 6, 25 : 26-3-acetoxy-27-oxy-26-methylcholestadiene-26-carboxylic acid lactone.  The unsaturated parent acids may be prepared by condensing cyclopentanopolyhydrophenanthrene ketones with halogenated fatty acid derivatives such as chloro-, bromo- or iodo acetic acid ester, a - or b -bromo-propionic acid ester, or -iso-butyric acid ester or -valeric-acid ester, methyl - ethyl - bromacetic acid ester, methyl-(a -bromethyl)- or methyl-(b -bromethyl) acetic acid ester, a - or b -bromo-isovaleric acid ester or bromo-triethyl-acetic acid ester, by the method of Reformatsky. They are also obtained by brominating the corresponding saturated acids and splitting off hydrogen bromide.  The Specification as open to inspection under Sect. 91 includes also the manufacture of compounds of the cyclopentanopolyhydrophenanthrene series in which the side chain set out above is attached at positions other than the 17-position. This subject-matter does not appear in the Specification as accepted.