Patent GB-997940-A (GB)
Title: Steroids containing a carbocyclic ring fused to the 16- and 17-positions
Inventor: ALLISON JAMES MACFARLANE
IPC: C07J75/00
Filed: 1963-04-10
Abstract: The invention comprises steroids having, apart from optional additional substituents and unsaturated linkages in rings C and D, the partial formula <FORM:0997940/C2/1> (wherein R is hydrogen, C1-6 alkyl or aryl) and their preparation by condensing a similar steroid of the partial formula <FORM:0997940/C2/2> (wherein R1 is H or CO2 alkyl and which, when R1 is H, may be in the 16-hydroxy-methylene form) with methyl vinyl ketone or an analogue thereof under basic conditions to yield a similar steroid of the partial formula <FORM:0997940/C2/3> and then cyclizing this with a strong basic reagent.  Hydroxy, aryloxy, alkoxy, formyl, alkyl, cycloalkyl, cycloalkylene, cyano, dialkylaminomethyl, alkenyl, alkynyl, and halo-alkynyl groups, halogen atoms and double bonds may be present at most other positions in the nucleus of the androstane or oestrane starting materials.  Keto groups must be protected by reduction to ols, ketals or enol ethers.  In the products 5-en-3-ols may be converted to 4-en-3-ones. The steroids may also have carboxylic or heterocyclic rings fused thereto, particularly to ring A. Examples are given, some of the hydroxy substituted products being converted to their acetates 21-Oximes, and 21-acetates of the 21-ols formed by reduction, are also described.  Steroids of the second partial formula above are prepared by treating the corresponding 16-unsubstituted-17-keto steroids with methyl or ethyl formate or diethyl oxalate in the presence of sodium hydride or sodium methoxide.  3,3 - Ethylenedioxy - 11b  - hydroxyandrost - 5 - en - 17 - one is prepared by reducing the ketal of cortisone acetate with sodium borohydride under vigorous conditions and oxidizing the product with sodium metaperiodate. 3,3-Ethylenedioxy - androst - 5 - en - 11,17 - dione is similarly prepared using mild reduction conditions. 3,3 - Ethylenedioxy - 11a  - hydroxyandrost - 5 - en - 17 - one is prepared similarly.  16 - (31 - Oxobutyl) - androsta - 1,4 - diene - 3,17-dione is prepared by oxidizing 16-(31-oxo-butyl) - 3b  - hydroxy - androst - 5en - 17 - one to give 16 - (31 - oxobutyl) - androst - 5 - ene - 3,17 - dione, converting this to 16 - (31 - oxobutyl) - androst - 4 - ene - 3,17 - dione and dehydrogenating this.  11b  - hydroxy - 16 - (31 - oxobutyl) - androsta - 1,4 - diene - 3,17 - dione is prepared by dekalizing 3,3-ethylenedioxy-11b -hydroxy-16 - (31 - oxobutyl) - androst - 5 - en - 17 - one to give 11b -hydroxy-16-(31-oxobutyl)-androst-4-ene-3,17 -dione, and then dehydrogenating this with dichlorodicyanoquinone. Dehydrogenation with chloranil gives 11b -hydroxy-16-(31-oxo-butyl) - androsta - 4,6 - diene - 3,17 - dione.  6 - Formyl - 11b  - hydroxy - 3 - methoxyandrosta-3,5-dien-17-one is prepared from the corresponding 6-unsubstituted compound and the Vilsmeier reagent, the product being treated with methanolic potassium hydroxide. 6-Cyano-11b  - hydroxy - 3 - methoxyandrosta - 3,5 - dien -17-one is prepared by treating the above 6-formyl compound with hydroxylamine hydrochloride to give the 6-hydroxyiminomethyl compound, acetylating this, and heating the product at 175 DEG  C.