Patent GB-779941-A (GB)
Title: Manufacture of degradation products of tetracyclic triterpenes
IPC: C07J9/00
Filed: 1952-05-07
Abstract: The invention comprises acids and ketones obtained as degradation products from trisnorlanostanic acids of the formula R-CH(CH3)-CH2-CH2-COOH where R is the lanostane ring-system, probably <FORM:0779941/IV(b)/1> (which may be substituted), by the following process: the acids or their functional derivatives are reacted with organometallic compounds to give carbinols which are dehydrated to olefines; the latter are a -halogenated with bromine or a halogenated acid amide or imide, hydrogen halide is eliminated and the resulting dienes oxidized, whereby the side chain becomes -CO-CH3.  The process may be continued by condensing with an aldehyde to give -CO-CH=CH-, reducing the keto group to carbinol, eliminating water and oxidizing the diene to give =CH-CHO and =O in the 17 - position.  As an alternative, instead of oxidizing the diene to an acetyl group, it or the preceding ketone is a -halogenated, hydrolysed and oxidized to carboxylic acid.  The acetyl group itself may also be oxidized to carboxylic acid.  The starting materials may be modified by oxidation to a 7 : 11-diketone, hydrogenation of nuclear double bonds and etherification or esterification of hydroxyl groups.  In the examples: (1) trisnor-lanostane-dionic acid methyl ester or its 3-acetoxy derivative is treated to modify the side-chain as follows: treatment with phenylmagnesium bromide to give 1 - methyl - 4 : 4 - diphenyl - 4 - hydroxy - butyl, dehydration with iodine to 1-methyl-4 : 4-diphenyl-3-butenyl, treatment with N-bromsuccinimide to yield 1-methyl-4 : 4-diphenylbutadienyl, oxidation with chromic acid to acetyl and further treatment with iodine and alkali to form a 17-carboxyl group, finally esterified with diazomethane; the carboxylic acid may also be obtained from the butadienyl compound by halogenation, hydrolysis and oxidation; (2) the 17-acetyl compound of (1) is treated with benzaldehyde to give 17-cinnamoyl, reduced with aluminium isopropoxide to the carbinol and dehydrated to the g -phenylpropadienylidene group; the two nuclear keto groups are reduced with lithium aluminium hydride and one of the resulting hydroxy groups acetylated; ozonolysis followed by treatment with zinc and acetic acid oxidizes the remaining nuclear hydroxyl to keto and the side-chain to =CH-CHO and partly to =O (completed by a second ozonolysis); the nuclear acetoxy group is finally hydrolysed to hydroxy; (3) the 3-acetoxy starting material of (1) is treated with ethane-dithiol and the resulting cyclic thioketal group eliminated with Raney nickel; alkaline hydrolysis of the carboxylic ester and 3-acetoxy groups is followed by re-esterification of either one or the other; the 3-hydroxy-23-carbomethoxy compound is converted to the diphenylcarbinol as in (1), 3-acetylated and dehydrated to the butenyl derivative (optionally hydrolysed to 3-hydroxy), further dehydrogenated with N-bromsuccinimide to the butadienyl compound (optionally hydrolysed to 3-hydroxy) and finally oxidized with chromic acid to the 17-acetyl compound; the latter is either hydrolysed to 3-hydroxy and oxidized to 3-keto or as in (1) condensed with benzaldehyde, reduced with aluminium isopropoxide, dehydrated, ozonized and reductively acetylated to the 3-acetoxy-17-keto compound (with some =CH-CHO); the product is finally reduced to 3-hydroxy and oxidized to 3-keto; the other nuclear keto group is unchanged throughout the reactions.