Patent GB-554337-A (GB)
Title: Manufacture of saturated and unsaturated pregnane-polycarbonyl compounds and substitution products thereof
IPC: C07J75/00
Filed: 1941-01-17
Abstract: 554,337. Pregnane polycarbonyl compounds. SOC. OF CHEMICAL INDUSTRY IN BASLE. Jan. 17, 1941, Nos. 663 and 664. Convention dates, Jan. 17, 1940, and Nov. 20, 1940. [Class 2 (iii)] Saturated or unsaturated pregnane-polycarbonyl compounds are prepared by treating a pregnane-20-one containing in the 5-position a free, esterified or etherified tertiary hydroxyl group but no other substituent in rings A or B first with a reducing agent to convert the 20- keto group into a carbinol group and then with an agent which causes the elimination of water, acid or alcohol to eliminate the 5-substituent. The unsaturated compound so obtained is oxidized with an agent known to be suitable for introducing in α-position to the double linkage an oxo group or a free or esterified hydroxyl group and finally when the product contains no or only one keto group, it is treated with an oxidizing or dihydrogenating agent to convert a free hydroxyl group or groups in ring A or B and/or in the 20-position into a keto group or groups, if required after hydrolysis. The treatment of the unsaturated compound formed by the elimination of the 5- hydroxyl group may be modified in that an oxidizing agent is used which is known to be suitable for causing the addition of oxygen or free or esterified hydroxyl groups to a double linkage. In this case the product is treated with an agent which causes the elimination of water from free or partially esterified vicinal hydroxy groups, and/or with an oxidizing or dehydrogenating agent to convert a free hydroxyl group into a keto group. The 20-carbinol group may be esterified or etherified during or after the above operations. The parent materials for the process of the invention may be prepared as described in Specification 550,478. Agents mentioned as suitable for converting the 20-keto group into a carbinol group include reducing agents and metal hydrocarbon compounds such as Grignard reagents, also biochemical and electrochemical processes. After this first reduction step the 20-carbinol group is protected by esterification or etherification if the oxidizing agent used in the next stage is such as to render this necessary. As esterification agents numerous aliphatic and aromatic acids are mentioned and as etherification agents aliphatic or aliphatic-aromatic alcohols may be used. Oxidizing agents mentioned as suitable for introducing an oxo-group include chromicacid, selenium dioxide and the lead tetraacylates. These lead to the formation of compounds containing in α-position to the double linking a keto, hydroxyl, or esterified hydroxyl group. Oxidizing agents used to add on oxygen or a free or esterified hydroxyl group directly at the double linkage include hydrogen peroxide alone or in the presence of an alkali or metal oxide, per acids, halogens, metal oxides such as osmium tetroxide or vanadic acid, in some cases in the presence of a chlorate, also permanganates and silver halide benzoate complexes. In examples (1) 5-Oxy-pregnane-20- one is hydrogenated in alcohol solution in the presence of a nickel catalyst to form a mixture of epimeric pregnane -5 : 20-diols which on heating with propionic anhydride form a mixture of epimeric #<SP>4</SP>-pregnene-20-ol-propionates. This is oxidized by lead tetra-acetate in glacial acetic acid to form #<SP>4</SP>-pregnene-3:20-diol-3- acetate-20-propionate, which may be saponified with alcoholic potassium hydroxide and the diol so obtained oxidized with chromic acid to #<SP>4</SP>-pregnene-3:20-dione. (2)5-Oxy-pregnene- 20-one is reduced as in example (1) and the mixture of epimeric pregnane 5:20-diols heated with methyl alcoholic hydrochloric acid to give #<SP>4</SP>-pregnene-20-ol which is oxidized by chromic acid to progesterone. (3) The #<SP>4</SP>- pregnene-20-ol obtained in example (2) is oxidized with osmium tetroxide to form a mixture of pregnane-4:5:20-triols. Oxidation by chromic acid then yields progesterone.