Patent GB-957187-A (GB)
Title: New cyclohemiacetals and cyclohemiacetal esters of the pregnane series and process for their manufacture
IPC: C07J75/00
Filed: 1960-08-29
Abstract: The invention comprises 18(21)-cyclohemiacetals and 18(21)-cyclohemiacetal esters of 18, 20-dioxo-21-hydroxy-pregnanes which contain in the 3-position a free or esterified hydroxyl group or a free, ketalized or enolized oxo group, and 20-ketals thereof; and their preparation by dehydrogenating with a compound of hexavalent chromium in the presence of a diluent a 20-ketal of an 18, 21- dihydroxy-20-oxo-pregnane containing in the 3-position a free or functionally converted hydroxyl or oxo group to yield the 18(21)-cyclohemiketal of a 20-ketalized 18-oxo-21-hydroxy-20-keto-pregnane, and hydrolysing the 20-ketal group with a strong inorganic acid in the presence of a lower aliphatic carboxylic acid if desired after esterification of the 18(21)-cyclohemiacetal group.  Ester groups may subsequently be hydrolysed and free hydroxyl groups again esterified and/or free oxo groups ketalized.  In examples (1) D 5-3,3:20,20-bisethylenedioxy-11b , 18, 21-trihydroxy-pregnene is oxidized to the 18(21)-cyclohemiacetal of D 5-3,3:20,20-bisethylenedioxy-11, 18-dioxo-21-hydroxy-pregnene, this is deketalized to give the 18(21)-cyclohemiacetal of D  4-3, 11, 18-trioxo-20, 20-ethylenedioxy-21-hydroxy-pregnene, this is acetylated to the 18-acetate, this is deketalized to D  ha4-3, 11, 20-trioxo-18-acetoxy-18, 21-oxido-pregnene, this is hydrolysed to the 18(21)-cyclohemiacetal of D 4-3, 11, 18, 20-tetraoxo-21-hydroxy-pregnene (which may be re-acetylated to the 18-acetate), this is re-ketalized to give the first product of this example, this is reduced to the 11b -ol and this is acetylated and deketalized to give 21-O-acetyl-aldosterone; similarly D 5-3, 3:20, 20-bisethylenedioxy-11b -acetoxy-18, 21-dihydroxy-pregnene (obtained from the corresponding 11b , 18, 21-trihydroxy compound by acetylation and then partial hydrolysis of the 11, 21-diacetate) is converted to D 4-3, 20-dioxo-11b , 18-diacetoxy-18, 21-oxido-pregnene; (2) the starting material of (1) is oxidized to D 5-3, 3:20, 20-bisethylenedioxy-11-oxo-18, 21-dihydroxy-pregnene (which on hydrolysis gives D 4-3, 11-dioxo-18, 21-dihydroxy-20, 20-ethylenedioxypregnene which can also be used as starting material in this example), this is oxidized to the 18(21)-cyclohemiacetal of D 5-3, 3:20, 20-bisethylenedioxy-11, 18-dioxo-21-hydroxypregnene (which is converted to the 18-tetrahydropyranyloxy derivative, the latter reduced to D 5-3, 3:20, 20-bisethylenedioxy-11b -hydroxy-18-tetrahydropyranyloxy-18, 21-oxido-pregnene and this converted to aldosterone), this is deketalized to D 4-3, 11, 20-trioxo-18-acetoxy-18, 21-oxido-pregnene and this is hydrolysed as in (1); and (3) D 5-3, 3:20, 20-bisethylenedioxy-11a - 18, 21-trihydroxypregnene (prepared by reduction of the 11-oxo compound and converted, if desired, into the 20-monoketal) is oxidized and deketalized to give D 4-3, 11, 20-trioxo-18-acetoxy-18, 21-oxido-pregnene. The preparation of 3b -benzoyloxy-18-acetoxy-11, 20-dioxo-18, 21-oxido-5a -pregnane and 3, 11, 20-trioxo-18-acetoxy-18, 21-oxido-5a -pregnane is also referred to. The pregnene derivatives of the invention, some of which are stated to have an adrenocortical action, may be made up into pharmaceutical compositions with suitable carriers. These may take the form of tablets, dragees, solutions, suspensions or emulsions, and may contain preserving, stabilizing, wetting or emulsifying agents, salts for varying the osmotic pressure or buffers.  Specifications 936,345 and 957,188 are referred