Patent GB-1007016-A (GB)
Title: 18-substituted steroids and process for their manufacture
IPC: C07J5/00
Filed: 1961-12-14
Abstract: The invention comprises 18-iodo-20-hydroxy- and 18-iodo-20-oxo-compounds of the pregnane series, the preparation of the 20-hydroxy-compounds by treating an 18-unsubstituted-20-hydroxy-pregnane with a substance capable of forming monovalent, positive iodine under conditions that will cause homolytic cleavage of any 20-hypoiodite formed, the treatment being discontinued while unchanged pregnane starting material can still be detected in the reaction mixture, the preparation of the 20-oxo-compounds by oxidation of the 20-hydroxy-compounds with a compound of hexavalent chromium, and if desired, acylation of the 20-hydroxy-compounds to form 18-iodo-20-acyl-oxy-pregnanes or treatment of the 20-hydroxy-compounds with an alkaline hydrolysing agent to form 18,20-oxido-pregnanes, or treatment of the 20-oxo-compounds with an alkaline hydrolysing agent to form 18-hydroxy-20-oxo-pregnanes or semi-ketals of 18-hydroxy-20-oxo-pregnanes or 20-ethers thereof.  Substances capable of forming monovalent, positive iodine are N-iodo-carboxylic acid amides and imides, cyanogen iodide, alkyl hypoiodites (prepared, for example, from heavy metal oxides, iodine and alcohols), iodine halides and, particularly, acyl hypoiodites, advantageously obtained from heavy metal acylates, e.g. silver and mercury acylates, lead tetraacylates, and iodine. The reaction with these reagents must be stopped by destroying the excess reagent, for example by agitating the reaction solution with a reducing agent or by reducing the quantity of active reagent, e.g. by using an oxidizing lead acylate in the presence of less than 1 molecular equivalent of iodine calculated on the 20-hydroxy compound, otherwise 18-iodo- or 18-hydroxy-18,20-oxido-pregnanes are formed, as described in Specification 973,143.  Hydrolysis of the 18-iodo-20-hydroxy-compounds to 18,20-oxido-pregnanes may be effected with an inorganic or organic base, or a metal salt of a carboxylic acid in a solvent, which reagents may also be used to convert 18-iodo-20-oxo-compounds to semi-ketals of 18-hydroxy-20-oxo-pregnanes, or, when an alcohol is used as solvent, their 20-ethers, which can be split by acid hydrolysis to the free semi-ketals, these being interconvertable with the 18-hydroxy-20-oxo-pregnanes. Ketalized oxo groups may be converted to free oxo groups in the hydrolysis. The starting materials for the present process may be 20a - or 20b -hydroxy compounds of the 5a - or 5b -pregnane series or pregnanes containing a D 4- or D 5-double bond, or the corresponding 19-nor or 21-nor compounds, and they may contain esterified or etherified hydroxyl groups, free or ketalized oxo groups, alkyl groups or halogen atoms at one or several positions of the steroid nucleus or 17-side chain, or further double bonds, or oxido groups, e.g. D 9(11) and D 1, and 9,11-epoxides. Examples are given, by products in the reaction with iodine compounds being the 18-hydroxy-18,20-oxido-pregnanes and 18, 20-lactones of 20-hydroxy-pregnane-18-acids described in Specifications 973,143, 973,144 and 973,145, and 20-ketones corresponding to the 20-hydroxy starting materials.  Also described are (1) the treatment of 3a ,11a -diacetoxy-18,20-oxido-5b -pregnane with acetic anhydride and boron trifluoride etherate to give 3a ,11a ,18, 20a -tetraacetoxy-5-b -pregnane; (2) the isolation of 3b ,11a  - diacetoxy - 17 - iodo - 5a - androstane as a by-product in the oxidation of 3b ,11a  diacetoxy - 18 - iodo - 18,20b  - oxido - 5a  - pregnane; and (3) the preparation of D 5-3b -acetoxy-20-hydroxy-pregnene by reduction of the 20-ketane; other starting materials are prepared similarly.