Patent GB-464271-A (GB)
Title: Process for the reduction of saturated and unsaturated germinal gland hormones containing at least one keto group, their isomers and derivatives
IPC: C07J1/00
Filed: 1935-10-10
Abstract: Saturated or unsaturated hydroxy compounds of the cyclopentanopolyhydrophenanthrene series are produced by reduction with hydrogen in the presence of alloy-skeleton catalysts of saturated or unsaturated germinal gland hormones respectively, containing at least one keto group or derivatives thereof in which the hydroxyl group is replaced by a group which on hydrolysis is reconverted into a hydroxyl group, such as ethers, esters or halogen derivatives, with the exception of androstenolone derivatives.  The catalysts are preferably prepared by alloying one or more metals which are capable of decomposing water or aqueous alkaline solutions with one or more metals which do not so react, and dissolving out therefrom the soluble component.  Suitable alloys are those of nickel with aluminium, nickel with silicon, cobalt with aluminium or silicon, and nickel and cobalt with silicon.  The preferred catalysts are those prepared according to the method of Raney.  The composition of the catalysts may vary widely but the preferred composition is a mixture of equal parts of the components.  Other alloy skeleton catalysts may also be employed such as that obtained from copper chromate by ignition followed by reduction.  The reduction is preferably carried out in solution, the solvents used being such as do not attack the catalyst, for example alcohols, and alicyclic hydrocarbons such as cyclohexane.  The temperature is preferably maintained below 50 DEG  C., but is regulated by a consideration of the activity of the catalyst.  Hormones mentioned as suitable starting materials for the process of the invention are the follicle hormones, equiline, equilenine, androsterone, dehydroandrosterone and their stereo-isomers such as trans-androsterone.  Diketones such as the androstandiones and androstendiones may also be used.  The above compounds may have been prepared either by extraction from natural sources or by synthesis.  It is stated that the process according to the present invention almost completely eliminates the danger of a simultaneous reduction of the nuclear double bond and the keto group when treating unsaturated starting materials.  In examples: (i) Hydrogen is passed into a solution of androstenolone in ethanol at about 20 DEG  C.  The reduction stops when 1 mol. of hydrogen has been absorbed, and the product after the removal of the catalyst consists almost entirely of androstendiol; (2) Androsterone benzoate is reduced in ethanol solution in the pressure of cobalt-nickel skeleton catalyst at room temperature and normal pressure, to give androstandiol monobenzoate; (3) Follicle hormone benzoate is reduced as described in example (1) to give dihydrofollicle hormone monobenzoate; (4) Androstandione in ethanol solution is shaken with hydrogen in the presence of Raney catalyst until no further absorption takes place.  After removal of the catalyst there remains transandrostandiol; (5) Androstandione in ethanol solution is shaken with hydrogen in the presence of Raney catalyst until the absorption of hydrogen amounts to 1 mol.  The product consists of transandrosterone; (6) The oil obtained as a residue in the production of crystallized follicle hormone is reduced in ethanol solution in the presence of Raney catalyst until no further absorption of hydrogen takes place.  A product with a physiological activity of 2\ba1/2\be times that of the starting material is obtained.  Specifications 427,561, 427,588, 428,132, 429,747, and 443,463, are referred to.  Reference has been directed by the Comptroller to Specification 454,632 as open to inspection under Sect. 91 of the Acts).ALSO:Saturated or unsaturated hydroxy compounds of the cyclopentanopolyhydrophenanthrene series are produced by reduction with hydrogen in the presence of alloy-skeleton catalysts of saturated or unsaturated germinal gland hormones respectively, containing at least one keto group or derivatives thereof in which the hydroxyl group is replaced by a group which on hydrolysis is reconverted into a hydroxyl group, such as ethers, esters or halogen derivatives, with the exception of androstenolone derivatives.  The catalysts are preferably prepared by alloying one or more metals which are capable of decomposing water or aqueous alkaline solutions with one or more metals which do not so react, and dissolving out therefrom the soluble component. Suitable alloys are those of nickel with aluminium, nickel with silicon, cobalt with aluminium or silicon, and nickel and cobalt with silicon.  The preferred catalysts are those prepared according to the method of Raney.  The composition of the catalysts may vary widely but the preferred composition is a mixture of equal parts of the components.  Other alloy skeleton catalysts may also be employed such as that obtained from copper chromate by ignition followed by reduction.  The reduction is preferably carried out in solution, the solvents used being such as do not attack the catalyst, for example alcohols, and alicyclic hydrocarbons such as cyclohexane.  The temperature is preferably maintained below 50 DEG  C. but is regulated by a consideration of the activity of the catalyst.  Hormones mentioned as suitable starting materials for the process of the invention are the follicle hormones, equiline, equilenine, androsterone, dehydroandrosterone and their stereo - isomers such as trans - androsterone. Diketones such as the androstandiones and androstendiones may also be used.  The above compounds may have been prepared either by extraction from natural sources or by synthesis.  It is stated that the process according to the present invention almost completely eliminates the danger of a simultaneous reduction of the nuclear double bond and the keto group when treating unsaturated starting materials.  In examples: (1) hydrogen is passed into a solution of androstenolone in ethanol at about 20 DEG  C.  The reduction stops when 1 mol. of hydrogen has been absorbed, and the product after the removal of the catalyst consists almost entirely of androstendiol; (2) androsterone benzoate is reduced in ethanol solution in the pressure of cobalt-nickel skeleton catalyst at room temperature and normal pressure, to give androstandiol monobenzoate; (3) follicle hormone benzoate is reduced as described in example (1) to give dihydrofollicle hormone monobenzoate; (4) androstandione in ethanol solution is shaken with hydrogen in the presence of Raney catalyst until no further absorption takes place.  After removal of the catalyst there remains trans-androstandiol; (5) androstandione in ethanol solution is shaken with hydrogen in the presence of Raney catalyst until the absorption of hydrogen amounts to 1 mol.  The product consists of transandrosterone; (6) the oil obtained as a residue in the production of crystallized follicle hormone is reduced in ethanol solution in the presence of Raney catalyst until no further absorption of hydrogen takes place.  A product with a physiological activity of 2\ba1/2\be times that of the starting material is obtained.  Specifications 427,561, 427,588, 428,132, 429,747, 443,463, and 448,183, [all in Group IV], are referred to. Reference has been directed by the Comptroller to Specification 454,632, [Group IV].