Patent GB-929273-A (GB)
Title: Steroids and their production
IPC: C07J43/00
Filed: 1959-04-12
Abstract: <FORM:0929273/IV(a)/1> <FORM:0929273/IV(a)/2> <FORM:0929273/IV(a)/3> <FORM:0929273/IV(a)/4> <FORM:0929273/IV(a)/5> The invention comprises 10a -methyl-9a -steroids of the general formula III and IV shown in the Figure, wherein R2 represents no double bonds or one or more double bonds at one or more of the positions 1, 3, 4, 5 and 6, R4 represents a keto, hydroxy, etherified hydroxy or esterified hydroxy group, and QIII represents a hydrogen or halogen atom, or a hydroxy or O-alkyl group, QV represents a hydrogen atom and QIV represents a secondary amine residue (including cyclic amine), or an O-acyl, phenyl or alkyl group, or QIV and QV each represent a phenyl or alkyl group; the preparation of the compounds of formula III, wherein QIII represents a hydrogen atom or a hydroxy group, by oxidising 10a -methyl-9a -steroids of the general formula II shown in the Figure, wherein QI and QII each represent an aliphatic hydrocarbon group having from 1 to 6 carbon atoms or QI may represent a hydrogen atom and QII is as previously defined; the preparation of the compounds of formula IV, wherein QIV represents the secondary amino group and QV represents a hydrogen atom by reacting compounds of formula III, wherein QIII represents hydrogen, with a secondary amine; the preparation of the compounds of formula IV, wherein QIV represents an O-acyl group and QV represents hydrogen, by reacting compounds of formula III, wherein QIII represents hydrogen with an acid anhydride; the preparation of the compounds of formula IV wherein QIV and QV each represent the same alkyl or phenyl group or one represents such a group and the other hydrogen, by reacting compounds of the formula III, wherein QIII represents a hydrogen atom or an O-alkyl group, with a phenyl or alkyl Grignard reagent and decomposing the reaction product in an acidic or neutral medium; and the preparation of compounds of formula IV, wherein QIV represents a phenyl group and QV represents a phenyl or alkyl group, by reacting compounds of formula III, wherein QIII represents a halogen atom, with diphenyl cadmium, reacting the resulting intermediate ketone with a phenyl or alkyl Grignard reagent, and decomposing the reaction product in a neutral or acidic medium.  The compounds of formula III, wherein QIII represents a halogen atom or an O-alkyl group, are prepared by halogenating or esterifying the corresponding compound of formula III, wherein QIII represents a hydroxy group.  In the oxidation processes referred to above, it is preferably to protect a 4(5) double bond in the absence of a 3-keto group, for example, by conversion to a dibromide from which the bromine atoms can be removed at a later stage by the action of zinc dust in glacial acetic acid, or by conversion into an epoxide by reaction with hydrogen peroxide in alkaline medium and subsequent decomposition by reaction of the epoxide with potassium iodide in a weakly acidic medium. Oxidation with chromium trioxide, potassium or sodium dichromate, or potassium permanganate forms acids of the formula III, i.e. QIII represents a hydroxy group, or oxidation with ozone forms an ozonide which may be decomposed to form an acid or aldehyde of formula III, i.e. QIII represents a hydroxy group or a hydrogen atom, by means of oxidising or reducing agents, for example, oxidising agents such as hydrogen peroxide or an alkaline solution of potassium permanganate, and reducing agents such as zinc dust-glacial acetic acid, iron powder in sulphuric acid, and aldehydes.  Following the above processes, a 3-hydroxy group may be oxidised to a 3-keto group, for example, by means of manganese dioxide.  In the examples the compounds of the formulae XVI and XVII shown in the Figure are prepared.  D 4,22-Pyrostadiene-3-one is prepared by oxidising pyrocalciferol with cyclohexanone and aluminium isopropylate to form D 4,7,22-pyrostatriene-3-one, treating this compound with dry hydrogen chloride in isopropanol to form D 4,6,22-pyrostratriene-3-one, reducing this compound with lithium in liquid ammonia to form D 5,22-pyrostadiene-3-one, and isomerising this compound in an alkaline or acidic medium.  Specifications 929,271 and 929,275 also are referred to.