Patent GB-567393-A (GB)
Title: Manufacture of compounds of the cyclopentanopolyhydro-phenanthrene series
IPC: C07J3/00
Filed: 1942-11-06
Abstract: Compounds of the cyclopentanopolyhydrophenanthrene series are prepared by subjecting to side chain degradation preferably in stages by the methods of Wieland Hoffmann or Curtius, or by oxidative degradation, compounds of the cholenic acid series which are substituted in ring A and unsaturated in ring C.  The parent materials for the process of the present invention may be prepared as described in the parent Specification.  These compounds contain a free or esterified hydroxyl group in 12-position and also in the 3- and/or the 7-position.  Compounds mentioned include D 11 : 12-3-oxy-cholenic acid, D 12 : 12-3-ketocholenic acid, D 11 : 12-3 : 7-di-oxy-cholenic acid, D 5 : 6, 11 : 12 - 3 - oxy - choladienic acid, D 4 : 5, 11 : 12 - 3 - keto - choladienic acid, D 5 : 6, 11 : 12 3 : 7 - dioxy - choladienic acid, D 4 : 5, 11 : 12 - 3 : 7 - diketo - choladienic acid.  Instead of compounds of the cholanic acid series, lower homologues obtained by partial side chain degradation may be used.  Sensitive substituents such as hydroxyl or keto groups and also double linkages may be protected during the oxidation.  In examples: (1) the double bond in D 11 : 12-3-acetoxy cholenic acid methyl ester is protected by bromine and the dibromo compound oxidized by chromic acid in glacial acetic acid to give as neutral products D 11 : 12 - 3 - oxy - androstene - 17 - one, and also D 11 : 12-3-oxy-pregnene-20-one.  Acid products are also obtained consisting of D 11 : 12-3-oxy-etiocholenic acid, which on oxidation forms the corresponding 3-keto compound; (2) D 11 - 12-3-oxy-cholenic acid methyl ester is run into phenyl magnesium bromide and there is thus obtained D 11 : 12-3-oxy-norcholenyl-diphenyl carbinol.  This compound is acetylated in the crude state by treatment with acetic anhydride p  in pyridine to form the 3-monoacetate.  This is dehydrated by boiling with glacial acetic acid to form the ethylene compound which is then oxidized with chromic acid to form D 11 : 12-nor-lithocholic acid.  Treatment with diazomethane and acetylation is then carried out and on the resulting compound three is allowed to act phenyl magnesium bromide to effect a further degradation to the bisnor acid.  A similar sequence of reactions results finally in the formation of D 11 : 12-3-oxy-etio-cholenic acid methyl ester. Samples have been filed under Sect. 2 (5) of D 9 : 11-3a -acetoxy - etiocholenic acid methyl ester and D 9 : 11 - a  - ocetoxy - 12 - keto - etiocholenic acid methyl ester which are prepared as follows: D 9 : 11-3a -oxy-cholenic acid methyl ester is treated with phenyl magnesium bromide in ether and worked up in the usual way to form D 9 : 11 - 3a  - oxy - norcholenyl - diphenyl carbinol.  This is acetylated, oxidized with chromium trioxide and the acid products methylated with diazomethane.  There are thus obtained D 9 : 11 - 3a - acetoxy - norcholenic acid methyl ester and D 9 : 11-3a -acetoxy-12-ketonorcholenic acid methyl ester which are separated chromatographically.  The first of these compounds is saponified, re-methylated and then oxidized with chromium trioxide to form D 9 : 11 - 3 - acetoxy - bisnorcholenic acid methyl ester and D 9 : 11-3a -acetoxy-12-ketobisnorcholenic acid methyl ester which are separated chromatographically.  The first of these compounds is then further degraded by a repetition of the above process to yield the two required products which are separated as before.