Patent GB-517288-A (GB)
Title: Manufacture of polyoxy compounds of the cyclopentanopolyhydrophenanthrene series andderivatives thereof
IPC: C07J1/00
Filed: 1938-07-18
Abstract: 517,288. Hydroxy cyclopentanophenanthrene compounds. SOC. OF CHEMICAL INDUSTRY IN BASLE. July 18, 1938, Nos. 21249 and 21250. Convention dates, July 17, 1937, and June 15, 1938. [Class 2 (iii)] Polyoxy-compounds of the cyclonentanopolyhydrophenanthrene series are prepared by reducing a compound of this series which contains in a side chain attached to the 17-position a free or substituted alpha-oxyketo group or an alpha-keto-aldehyde group. The product thus obtained may be subjected to saponification and/or esterification or etherification. Reducing agents mentioned as suitable for the process of the invention include metals such as alkali metals, zinc, iron, magnesium, copper, or alloys thereof, in the presence of alcohols, moist ethers, dilute acids or alkalies, organic acids such as glacial acetic acid or solutions of alkali salts of organic acids and ethers. There may also be used an alkali ammonium, an amalgam such as an alkali-, aluminium-, or magnesium amalgam in the presence of an acid or an alkali, or aluminiumisopropylate or -isobutylate in the presence of an alcohol. The reduction may also be performed electrolytically or catalytically by hydrogen in presence of nickel, cobalt, palladium or platinum, or by biochemical means, or by means of organo-metallic compounds, particularly those which tend to form unsaturated compounds. Nuclear keto groups may also undergo simultaneous reduction. Nuclear ester and ether groups may be saponified either in the course of or after the reduction step, and the glycols so formed may be re-esterified. For this esterification there may be used carboxylic acids such as acetic acid, propionic acid, valerianic acid, palmitic acid, crotonic acid, benzoic acid, phenylacetic acid, or a sulphonic acid such as methane sulphonic acid or toluene-sulphonic acid or a hydrohalogen acid, or phospboric acid or boric acid. Derivatives of these acids such as an acid anhydride, an acid halide or a ketone. Ether derivatives mentioned which may be prepared include' the methyl ethyl, cyclohexyl, and trityl ethers. In examples (1) an isobutyl alcohol solution of the 3-enol acetate of 17:21- diacetoxy-progesterone and aluminium isobutylate is heated under reflux to give the 3- enol acetate of #<4À5>-3-keto-pregnene 17:20:21- triol-17:21-diacetate, which is saponified to #<4À5>-pregnenone-3-triol 17:20:21. Instead of the 3-enol esters, the corresponding 3-enol ether may be used. The reduction may be carried out also in isopropyl alcohol or' cyclohexonol solution or may be done phytochemically by means of yeast and cane sugar, or catalytically using a nickel catalyst. In a completely analogous manner the reaction may be carried out with other nuclear hydroxyl substituted compounds. (2) #<5À6>-20:21-dioxo-pregnenol-3 is hydrogenated in alcoholic solution in presence of a nickel-cobalt catalyst to give A <5À6>-3:20:21- trioxy-pregnene. The #-oxyketones and ocketo-aldehydes used in the present invention may be prepared from the appropriate #- dihalogenketones or cc-diazo-ketones by replacing the halogen or the diazo group by oxygen as described in Specification 517,276, or by water as described in Specification 516,828. The Specification as open to inspection under Sect. 91 describes also the use as parent materials for the reduction process of the present invention oc-oxy-aldehydes, #-keto-ketones, # -oxy-, and #-keto-carboxylic acids of the cyclopentanopolyhydrophenanthrene series. The #-oxy groups may be esterified or etherified, and the carboxylic acids may be present as such or in the form of their halides, esters, amides, or anhydrides. Parent materials particularly mentioned include compounds of the saturated or unsaturated aetiocholane, oestrane, or hydro-oestrane series containing in positions 3, 11, 12, and/or 17 oxy groups, substituted oxy groups or keto groups, and having in the 17 and/or 3-positions the side chains:- where R represents hydrogen or a substitute or non-substituted hydrocarbon residue, and R<1> and R<11> may have the same significance as R and also acyl residues. The parent materials may be used in different stereoisomeric forms, particularly those which differ in configuration at carbon atoms, 3, 5, 9, 11, 12, 17 and/or 20. This subject-matter does not appear in the Specification as accepted.