Patent GB-807227-A (GB)
Title: Steroid campounds and processes for the manufacture thereof
IPC: C12P33/00
Filed: 1955-01-14
Abstract: The invention comprises a compound of the formula <FORM:0807227/IV (b)/1> wherein X is H2, O or <FORM:0807227/IV (b)/2> and R11 is H, OH, or an acyloxy radical, and a process for the manufacture of a 1,4-pregnadiene which comprises subjecting a pregnene of the formula <FORM:0807227/IV (b)/3> wherein X is H2, O, <FORM:0807227/IV (b)/4> y is 0, <FORM:0807227/IV (b)/5> and R11 is H, OH or Acyloxy, the dotted lines indicating the alternative positions of the double bond, to the action of a dehydrogenating micro-organism of the family Corynebacteriaceae, or its separate enzyme material, capable of introducing a double bond between the 1- and 2-carbons without degradation of the side chain or rupture of the nucleus.  Suitable microorganisms include the genera Corynebacterium, Listeria and Erysipelothrix, the last two of which genera include the species monocytogenes, rhusiopathiae, muriseptica and erysipeloidis. Preferred micro-organisms are Corynebacterium simplex and Corynebacterium hoagii.  The process may be effected by contacting the starting steroid with a growing culture of the micro-organism or with enzymes obtained therefrom.  The starting steroids may have -OH groups in 3, 11 and 21 positions, ester groups in 3 and 21 positions, and oxo groups in 3, 11 and 20 positions.  In the case of the starting steroid containing a 3-ester group, this is transformed into a 3-keto group.  Thus there is obtained 1,4-pregnadiene-11b ,21-diol-3,20-dione-21 - acetate; 1,4 - pregnadiene - 21 - ol - 3,20-dione - 21 - acetate; and 1,4 - pregnadiene - 21-ol - 3,11,20 - trione - 21 - acetate. Hydrolysis of a 21-ester group may take place according to to the pH and temperature employed.  The products of reaction may be recovered by extraction with a suitable water-miscible solvent, by filtration, or by adsorption on a suitable adsorbent.  Examples describe the conversion of D 1 - pregnen - 3b  - ol - 20 - one into D 1,4-pregnadiene - 3,20 - dione, D 1 - pregnene - 3b ,20-diol into D 1,4 - pregnadiene - 3,20 - dione, D 4-pregnene - 11b ,21 - diol - 3,20 - dione into D 1,4-pregnadiene - 3,20 - dione, D 4 - pregnene - 11b , 21 - diol - 3,20 - dione into D 1,4 - pregnadiene-11b ,21 - diol - 3,20 - dione, D 1 - pregnen - 21 - ol, 3,20 - dione into D 1,4 - pregnadien - 21 - ol-3,20 - dione and D 4 - pregnen - 21 - ol - 3,11,20-trione into D 1,4 - pregnadien - 21 - ol - 3,11,20-trione.  The hydroxylated products may be esterified by known methods to the corresponding esters, e.g. acetic acid esters.ALSO:The invention comprises a pharmaceutical preparation comprising a compound of the formula <FORM:0807227/VI/1> H, OH, or an acyloxy radical, mixed with a pharmaceutical carrier. The products may be administered orally, in the form of tablets containing a solid carrier such as starch, sugar, gums and clays; by injection, dissolved or suspended in a suitable non-toxic liquid vehicle, by subcutaneous implantation in solid form; as suppositories dissolved or suspended in a fatty or waxy vehicle which melts at approximately body temperature; or as an ointment or cream dissolved in an unguent or cream base of known composition.