Patent GB-1041278-A (GB)
Title: 13-alkyl steroid ketone derivatives
Inventor: HUGHES GORDON ALAN
IPC: A61K31/57
Filed: 1961-10-19
Abstract: Novel steroid compounds of the general formula <FORM:1041278/C2/1> wherein the lines connecting R1, R2, OH and H to the steroid nucleus have no configurational significance, R1 represents an alkyl group of at least 2 carbon atoms, R2 represents an unsubstituted or substituted alkyl, alkenyl or alkynyl group, R2 is trans to R1, the hydrogen atoms H and group R1 at the junctions in ring C are in the trans-antitrans-trans configuration, and X represents an acid-hydrolysable protected 3-oxo group which is accompanied by an ethylenic bond terminating at the 5-position with or without a second ethylenic bond terminating at the 3-position, are prepared by treating the corresponding 17-keto compounds with an organometallic reagent containing the group R2; by reducing the required steroids of the general formula <FORM:1041278/C2/2> wherein R is alkyl and R1 has the above significance by means of catalytic hydrogenation in a non-protonic solvent using a palladium or Raney nickel catalyst until sufficient hydrogen has been absorbed for saturation of the 14,15-ethylenic bond, by means of a carbonyl reducing agent, such as sodium borohydride or lithium aluminium hydride, before or after the catalytic hydrogenation, to convert the carbonyl group to a hydroxymethylene group, by means of alkali metal in liquid ammonia after the catalytic hydrogenation and simultaneously with or after the carbonyl-reducing step to saturate the 8,9-ethylenic bond, and by the action of alkali metal in liquid ammonia in the presence of a proton donor that is an alcohol having less than 6 carbon atoms simultaneously with or after saturation of the 8,9-ethylenic bond to form steroids of the formula <FORM:1041278/C2/3> selectively oxidizing these compounds to convert the hydroxymethylene group to a carbonyl group and treating the 17-keto compounds with an organometallic reagent containing the group R2 to form steroids of the formula <FORM:1041278/C2/4> wherein R is an alkyl group and R1, R2, ring C and the hydrogen atoms have the above significance; by treating the required steroids of either of the formulae <FORM:1041278/C2/5> <FORM:1041278/C2/6> wherein R1 and R have the above significance, with an alkylene glycol to form steroids of the formula <FORM:1041278/C2/7> wherein X is an alkylenedioxy group and ring B has an ethylenic bond terminating at the 5-position, oxidizing these compounds to form the corresponding 17-keto compounds and treating the 17-keto compounds with an organo-metal ethynylating agent; by reducing steroids of the general formula <FORM:1041278/C2/8> wherein RO represents an alkoxy group (R may be a substituted or unsubstituted alkyl, alkenyl or alkynyl group such as a methyl, ethyl, hydroxyethyl, 2,3-dihydroxypropyl or benzyl group), R2 represents an alkenyl or alkynyl group that is saturated at the carbon atom adjacent to the steroid nucleus, ring C is saturated or contains an ethylenic bond terminating at the 9-position and the configuration of the C: D ring junction and the hydrogens at C8, C9 and C14 have the above significance, according to the Birch method, e.g. an alkali metal in liquid ammonia in the presence of a proton donor, to form the corresponding compounds having double bonds in the 2(3)- and 5(10)-positions; and by selectively hydrogenating steroids of the first formula above wherein R2 represents an alkenyl or alkynyl group to form the corresponding compounds in which R2 is an alkyl group.  By "alkoxy" is meant the alcoholate radical derived from an alcohol.  In compounds of the first general formula above it is preferable for X to represent either a divalent organic radical linked to ring A by two oxygen or sulphur atoms or one oxygen and one sulphur atom with a single ethylenic bond terminating at the 5-position such as 3-ketals, 3-mercaptoles and 3-hemithioketals, or one divalent or two monovalent organic radicals linked to ring A by a nitrogen atom with two ethylenic bonds, one of which terminates at the 3-position and the other at the 5-position such as 3-enol ethers, 3-enol thioethers, 3-tertiary amino compounds and 3-enol acylates. The above formulae include all states of resolution except the resolved 13a -enantiomer.