Patent GB-1045174-A (GB)
Title: Improvements in or relating to 3,5-cyclo-6ª‰,19-oxido-steroids
IPC: C07J53/00
Filed: 1963-04-10
Abstract: The invention comprises (1) a process for the production of 3,5 - cyclo - 6b ,19 - oxido - androstanes, -pregnanes and -sapogenins which comprises treating the corresponding 3,5-cyclo-6b -hydroxy-steroids with a salt of one of the cations Pb+ + + +, Cu+ +, Cu+, Hg2, Ag+ Au+ and Au+ + + in a non-polar solvent; (2) the optional further process of reacting the products of (1) with acetic anhydride and Lewis acids to give the corresponding 3,5-cyclo-6b ,19-dihydroxy-steroids and then reacting these or the products of (1) directly with mineral acids or strong organic acids to give the corresponding 3b ,19-dihydroxy-D 5-steroids or their 3-acylates; and (3) steroids of the formulae <FORM:1045174/C2/1> <FORM:1045174/C2/2> <FORM:1045174/C2/3> <FORM:1045174/C2/4> wherein R is a ketonic group, a hydroxy group or an acyloxy group derived from a hydrocarbon carboxylic acid of less than 12 carbon atoms whic is optionally substituted; Q is a D 16 double bond or indicates the presence of a 17a -R1-16-R2 group, R1 being hydrogen, hydroxy or acyloxy as above defined and R2 hydrogen or a - or b -methyl, or R1 and R2 together being 16b ,17a -(di-C1- 8 alkyl-methylenedioxy), and Y is H2 or O. The starting materials for (1) must not have any other free hydroxy groups present, but may contain other substituents such as those in the above formulae, and halogen atoms at the 9a - and 21 - positions. Examples are given, and the conversion of the D 5-3b ,19-dihydroxy-steroids into 19-nor-D 4-3-ones by either (1) oxidation to D 4-19-al-3-ones and alkaline treatment of these; or (2) bromination to 5a ,6b -dibromo-3,19-diols, oxidation of these to 5a ,6b -dibromo-3-one-19-oic acids, debromination of these with zinc in acetic acid to give D 4-3-one-19-oic acids and decarboxylation of these in the presence of a mineral acid, is also described. 3,5-Cyclo-6b -hydroxy-steroids are prepared by tosylating 3b -hydroxy-D 5-steroids and hydrolysing the resulting 3-tosylates in presence of potassium acetate and preferably in aqueous acetone. 17,20; 20,21 - Bismethylenedioxy - D 5 - pregnen - 3b  - ol - 11 - one is prepared by converting cortisone to 17,20; 20,21 - bismethylenedioxy - D 4-pregnene -3,11-dione, converting this to 3-acetoxy - 17,20; 20,21 - bismethylenedioxy - D 3 5 - pregnandien -11 - one and reducing and hydrolysing this. The corresponding 11-unsubstituted compounds are prepared similarly.  The 17-acetate of 16a -methyl-D 5-pregnene-3b , 17a -diol-20-one is prepared by hydrolysis of the diacetate.  The 17-acetate of 16b -methyl-D 5 -pregnene-3b ,17-diol-20-one is prepared by converting 16b -methyl-pregnenolone to 3,20-diacetoxy - 16b  - methyl - D 5 17 (20) - pregnadiene, converting this to 3b ,20-diacetoxy-16b -methy-5a , 6a ; 17a ,20a  - bis - oxido - pregnane, treating this with methanolic KOH to give the 3-acetate of 16b  - methyl - 5a ,6a  - oxido - pregnane - 3b , 17a -diol-20-one, converting this to the 3-acetate of 16b -methyl - D 5 - pregnene - 3b ,17a  - diol-20-one, acetylating this to the di-acetate, and hydrolysing this.  The 17-acetate of D 5-androstene -3b ,17b -diol is prepared by preparing the 3-tetrahydropyranyl ether of D 5-androstene-3b -ol-one by etherification, reducing this to the 17b -ol, converting this to the 17-acetate and hydrolysing this.