Patent GB-929276-A (GB)
Title: Steroids and their production
IPC: C07J1/00
Filed: 1959-04-12
Abstract: <FORM:0929276/IV(a)/1> The invention comprises 10a -methyl-9a -steroids of the general formulae C and D shown in the Figure wherein QIII represents a hydrogen or halogen atom or a hydroxy or alkoxy group, QIV represents a secondary amine residue (including cyclic amine), an O-acyl group or a C1 to C6 alkyl or phenyl group and QV represents hydrogen, or QIV and QV each represent such alkyl or phenyl group, X has the formula shown in the Figure in which R1 represents a hydrogen atom or the methyl group, R2 represents no double bonds or one or more double bonds at one or more of the positions 1, 2, 3, 4, 5, 6, 7, 15 and 16, R3 represents a hydrogen atom or a methyl, ethyl, hydroxy, etherified hydroxy or esterified hydroxy group R4 represents a keto, hydroxy, etherified hydroxy or esterified hydroxy group, R5 represents a hydrogen or halogen atom, R6 represents a hydrogen or halogen atom or a methyl, hydroxy, etherified hydroxy or esterified hydroxy group, R7 represents hydrogen or a halogen atom, R8 represents hydrogen or a hydroxy or keto group, and R11 represents hydrogen or a hydroxy, etherified hydroxy or esterified hydroxy group; the preparation of the steroids of formula C, wherein QIII represents hydrogen or a hydroxy group, by oxidising 10a -methyl-steroids of the general formula B shown in the Figure wherein QI and QII each represent a lower aliphatic hydrocarbon group containing 1 to 6 carbon atoms or QI represents such a radical and QII represents a hydrogen atom and X has the above significance and, when required, reacting the compounds of formula C wherein QIII represents a hydrogen atom with the required secondary amine to form a compound of formula D wherein QIV represents a secondary amine residue and QV represents hydrogen, or with the required acid halide or anhydride to form a compound of formula D wherein QIV represents an O-acyl group and QV represents hydrogen, or with the required alkyl or phenyl Grignard reagent to form a compound of formula D wherein QIV represents the alkyl or phenyl group and QV represents hydrogen; the preparation of the compounds of formula D, wherein QIV and QV each represent the alkyl or phenyl group, by reacting compounds of the formula C, wherein QIII represents an alkoxy group, with the required phenyl or alkyl Grignard reagent; and the preparation of compounds of the formula D, wherein QIV and QV represent phenyl or alkyl groups which may be the same or different, by reacting a compound of formula C, wherein QIII represents halogen, with diphenylcadmium or a zinc Grignard compound to produce an intermediate ketone and reacting the ketone with the required phenyl or alkyl Grignard reagent.  The compounds of formula C wherein QIII represents an alkoxy group or a halogen atom are prepared by esterifying or halogenating the corresponding compound of formula C wherein QIII represents a hydroxy group.  In the oxidation processes referred to above, it is preferable to protect a double bond if it is not in conjunction with a 3-keto group or with a double bond, for example, by conversion to a dibromide and subsequent removal of the bromide, or by conversion to an epoxide and subsequent decomposition with potassium iodide in a weak acidic medium. Oxidation with chromium trioxide, potassium or sodium dichromate or potassium permanganate in acidic, neutral or alkaline media results in the formation of acids of the formula C, i.e., QIII is a hydroxy group, and oxidation with ozone forms an ozonide which may be decomposed to form an aldehyde or acid of formula C with oxidising or reducing agents, for example, oxidising agents such as hydrogen peroxide and alkaline permanganate form acids of formula C, and reducing agents such as zinc dust in acetic acid, iron powder in sulphuric acid and aldehydes, form aldehydes of formula C.  Before or after the processes referred to above it is possible to introduce a \D1-double bond by dehydrogenation with iodine pentoxide, iodic acid, selenic acid or selenium dioxide, or by biochemical dehydrogenation, or by dehydrohalogenation; to introduce at the 2-position an alkyl, halo, ester, hydroxy or ether substituent by reaction of a 3-ketone with an oxalic ester followed by either alkylation with an alkyl halide to form a 2-alkyl substituent or halogenation to form a 2-halo substituent which may then be converted to a 2-ester group, then hydrolysed to a 2-hydroxy group and finally etherified to a 2-ether group; to introduce a \D6-double bond by allylic halogenation of a \D4-compound followed by dehydrohalogenation; to oxidise a 3-hydroxy group to a 3-keto group; or to esterify a 3-hydroxy group.  In the examples the following compounds are prepared: 3-keto-lumi-bis-norchol-4-ene-22-al, 3-keto-lumi-bis-nor-chol-4-ene-acid, \D4,20(22)-22-(N-piperidino) -lumi-bisnorcholadiene-3-one, \D4,20(22) - lumi-bis-norcholadiene- 3-one- 22-O-acetate, 3-keto-lumibis-nor-chola-4,6-diene-22-al, and 22-(N-piperidino)-lumibis-nor-chola- 4,6,20(22)-triene-3-one. \D4,22-Lumistadiene-3-one is prepared by treating \D4,7,22-lumistatriene-3-one with dry hydrogen chloride in propanol to form \D4,6,22-lumistratriene-3-one and reducing this compound with lithium and liquid ammonia.  Specification 929,272 also is referred to.