Almestrone
Almestrone, also known as 7α-methylestrone, is a synthetic, steroidal estrogen which was synthesized in 1967 but was never marketed. It is used as a precursor in the synthesis of several highly active steroids.
Almestrone had application in the original synthesis of Tibolone by Organon. However this method of synthesis is now obsolete.
Synthesis
The original synthesis of almestrone is quite old and dates back to 1967: Aromatization method: Precursor:The dehydrogenation of testosterone propionate by chloranil gives the corresponding 4,6-diene, . Conjugate addition of methylmagnesium bromide gives, after saponification, 7-alpha-Methyltestosterone along with some of the 7β-epimer. Oxidation of the alcohol with pyridinium chlorochromate gives 7alpha-Methylandrost-4ene-3,17-dione, PC23383196. Oxidation with DDQ gives 7alpha-methyl-1,4-androstadiene-3,17-dione, PC54064745. It is likely that the direction of this second dehydrogenation is mandated by the presence of the methyl group at C-7; this group may hinder the approach of reagent to the center which would lead to the alternate diene. Ketalization with ethylene glycol afforded PC26864627. Elimination of the angular methyl group at C-19 with consequent aromatization is achieved by treatment of the diene with lithium in the presence of biphenyl. Dektalization afforded Almestrone .
It can also be made from dehydronandrolone acetate. 7a-Methyl-estra-4-en-3,17-dione is oxidized with a catalytic amount of a copper halide in the presence of oxygen.