Patent GB-556734-A (GB)
Title: Manufacture of compounds of the ring-d-homo-steroid series
IPC: C07J41/00
Filed: 1941-01-15
Abstract: 556,734. Ring D-homo steroid compounds. SOC. OF CHEMICAL INDUSTRY IN BASLE. Jan. 15, 1941, Nos. 558, 559, 560 and 561. Convention dates, Jan. 17, 1940, March 13, 1940, March 14, 1940, and Nov. 22, 1940. Sample furnished. [Class 2 (iii)] Compounds of the ring-D-homo steroid series are prepared from compounds of the cyclopentanopolyhydrophenanthrene series which contain in the 17-position a side chain having at the carbon atom adjacent to the ring a reactive monovalent substituent consisting of a free or substituted hydroxyl-, or amino group or halogen atom, by a process which is known to be capable, when applied to a cycloaliphatic ring compound containing a side chain substituted as above, of splitting off said substituent with simultaneous ring extension of the cycloaliphatic ring. For splitting off a halogen atom metals or their oxides or salts may be used. Metals mentioned include silver, lead, copper and zinc. Compounds of metals used include mercury oxide and silver nitrate. Compounds containing a hydroxyl group as the reactive substituent are treated by a catalytic material such as iodine, an acid agent such as an inorganic or an organic acid, or an acid anhydride or an acid halide. An amino group can be split off by the direct elimination of ammonia or. indirectly by means of intermediate products for example salts or quaternary ammonium bases. Alternatively the amines may be diazotized and the diazocompound split up. The products of the invention contain in the extended ring-D a newly introduced keto group, a free or substituted hydroxyl group or a double linkage depending on the nature of the agent used and on the nature of further substituent at the ring carbon atom carrying the side chain. Thus ring extended ketones are obtained when the substituent on position -17 is a free or substituted hydroxyl group, and ring extended free or substituted secondary alcohols, when the 17-carbon carries a hydrogen atom. Compounds containing a new double linkage may be further treated by the addition of oxygen to form oxides and glycols. Ketones may be reduced to secondary alcohols which can be esterified or etherified. Keto compounds may also be converted into enol-derivatives. The compounds of the invention show the same biological effects as the sex hormones. In examples (1) 3:17-dioxy-17-aminomethyl androstane acetate is treated with sodium nitrite in the presence of acid to give an oxyketone of the ring -D-homo steroid series. Acetylation with acetic anhydride in pyridine yields the corresponding acetate. (2) 3-Acetoxy-17-oxy- 17-aminomethyl acetate is treated with acid sodium nitrite as in example (1) to give the same acetylated ketone. (3) 3-Epi-17-dioxy- 17-aminomethyl androstane acetate is treated as in example (1) with acid sodium nitrite to give an isomer of the oxy-ketone obtained in example (1). (4) 17-Amino-methyl androstane- 3-one is treated with acid sodium nitrite to give an oxyketone of the ring-D-homo-steroid series. (5) #<SP>4</SP>-17-aminomethyl-androstene-3-one is treated with acid sodium nitrite to give an unsaturated ring-D-homo-steroid oxyketone. (6)#<SP>5</SP> - 17 - aminomethyl androstene - 3 - ol is treated with acid sodium nitrite to give an unsaturated ring-D-homo steroid-diol which may be diacetylated. (7) #<SP>4</SP>-17-oxymethyl androstene-3-one is distilled with anhydrous oxalic acid under reduced pressure to give a doubly unsaturated ring-D homo steroid having one double bond in ring-D. Treatments of this compound with osmium tetroxide gives an unsaturated ring-D-homo steroid diketone. This same diketone can also be obtained by the action of dehydrating agents on #<SP>4</SP>-17-oxymethyl - 17 - oxy - androstene - 3 - one. The diketone on treatment with ethyl orthoformate in benzene solution yields its 3-mono-enol ether. 3:17-Dioxy-17-aminoniethyl androstane acetate is prepared from # <SP>5</SP>-3: 17-dioxy-androstene-17- nitrile by hydrogenation to form 3:17-dioxy-17- aminomethyl androstane, which is acetylated to the triacetyl derivative by acetic anhydride in pyridine. 3- Acetoxy-17-oxy-17-aminomethyl androstane acetate is prepared by the reduction by hydrogen in the presence of a platinum oxide catalyst in acetic acid of A <SP>5</SP>-3-acetoxy-17-oxy-androstene- 17-nitrile. 3 - Epi - 17 - dioxy - 17 - aminomethyl - androstane acetate is prepared by the reduction by hydrogen in the presence of a platinum oxide catalyst in acetic acid of 3-epi-17-dioxyandrostane-17-nitrile. 17- Aminomethyl-androstane-3-one is prepared from 3-acetoxy allopregnane -21- acid methyl ester by alkaline saponification followed by Curtius degradation of the free acid with intermediate protection of the hydroxyl group and subsequent oxidation thereof. #<SP>4</SP> - 17 - Aminomethyl - androstene - 3 - one is prepared from A <SP>5</SP> -3-oxypregnane-21-acid by Curtius degradation with intermediate protection of the hydroxyl group followed by oxidation thereof. A sample has been furnished under Sect. 2 (5) of D-homo-oestrone, prepared by reaction of oestrone acetate with potassium cyanide in a mixture of alcohol and glacial acetic acid, followed by catalytic hydrogenation of the oestrone cyanhydrin-3-monoacetate and diazotization of the amine so produced, and finally by hydrolysis of the D-homo-oestrone acetate.