GB885782A - Improvements in or relating to androstenone and androstanone derivatives - Google Patents

Abstract

The invention comprises 19-nor-steroids of the general formulae <FORM:0885782/IV (b)/1> wherein R is an alkyl, alkenyl or alkynyl radical of less than 5 carbon atoms and R1 is an alkyl radical of less than 5 carbon atoms), but excludes 5a : 17b -dihydroxy-17a -(propynyl) and butynyl)-6b -alkyl-19-nor-androstan-3-ones. The D 4-3-ketones may be prepared from the corresponding 3-ethylenedioxy-5a -hydroxy compounds either directly by the action of a strong concentrated inorganic acid such as hydrochloric acid or by milder hydrolysis with a dilute inorganic, e.g. mineral, acid or a strong organic acid to give the 5a -hydroxy-3-ketones and then dehydration of these with a dilute base such as sodium hydroxide. In examples (1) and (2) 3-ethylenedioxy-17a -ethyl-19-nor-5-androsten -17-ol is prepared in the usual way from the D 4-3-ketone and then converted to the 5X : 6X-epoxide, this is reacted with a methyl Grignard reagent to give the corresponding 6b -methyl-5a -ol, this with acetic acid gives the 6b -methyl-5a -hydroxy-3-ketone and this is dehydrated and epimerized with dilute alcoholic KOH to 17b -hydroxy - 17a - ethyl - 6a - methyl - 19 - nor 4 - androsten-3-one; (3) the corresponding 17a -propyl compounds are similarly prepared; (4) -(6) b -methoxy-19-nor-2 : 5(10)-androstadien -17b -ol with ethylene glycol gives 3-ethylenedioxy -19-nor-5-androsten-17b -ol (also obtainable from the D 4-3-ketone), this is converted to the 17 -acetate, this to the 5a : 6 a -epoxide, this to the 6b -methyl-5a -ol and this by an Oppenauer oxidation to 3-ethylenedioxy-5a -hydroxy-6b -methyl - 19 - nor - androstan - 17 - one, this with 2-methallyl magnesium chloride gives 3-ethylene -dioxy - 17a - (2 - methallyl) - 6b - methyl - 19 - norandrostan -5a : 17b -diol or with the corresponding allyl Grignard reagent the 17a -allyl compound and these are converted as in examples (1) and (2) to the 6b -methyl-5a -hydroxy-3-ketones and the 6a -methyl-D 4-3-ketones, the 2-methallyl compound also being converted by catalytic hydrogenation to 17b -hydroxy-17a -isobutyl - 6a - methyl - 19 - nor - 4 - androstan - 3 -one; (7) 3-ethylenedioxy-5a -hydroxy-6b -methyl -19-norandrostan-17-one is reacted with acetylene to give 3-ethylenedioxy-17a -ethynyl-6b -methyl-19 -norandrostane-5a : 17b -diol and this is converted as in (1) and (2) to the corresponding 3-ketone and then the 6a -methyl-D 4-3-ketone; (8) the ethylenedioxy intermediate of (7) is reacted with methyliodide in presence of ethyl magnesium bromide to give 3-ethylenedioxy-17a -(1-propynyl) -6b - methyl - 19 - norandrostane - 5a : 17b - diol and this is converted directly by the action of hydrochloric acid to 6a -methyl-17b -hydroxy-17a -(1 - propynyl) - 19 - nor - 4 - androstan - 3 - one; and (9) 6a -methyl-17b -hydroxy-17a -(1-butynyl) -19-nor-4-androsten-3-one is similarly prepared.