Almestrone (INNTooltip International Nonproprietary Name) (developmental code namesBa 38372,Ciba 38372), also known as7α-methylestrone, is asynthetic,steroidalestrogen which was synthesized in 1967 but was never marketed.[1] It is used as aprecursor in thesynthesis of several highlyactive steroids.[2][3]
Almestrone had application in the original synthesis ofTibolone by Organon.[4][5][6] However this method of synthesis is now thought to be largely obsolete. Tibolone is used to synthesizeERA-63.
Almestrone has practical application in the synthesis ofDimethyldienolone &Dimethyltrienolone. They share the same precursor compound which is called 7alpha-Methyl-estra-4,9(10)-diene-3,17-dione.
Another use for almestrone is in the synthesis ofTAS-108.[9]
Almesterone methyl ether can be used to make 19-nor-D-homosteroids (c.f.mibolerone).[10]
The original synthesis of almestrone is quite old and dates back to 1967:[11][12] Aromatization method:[13] Precursor:[14]
The dehydrogenation oftestosterone propionate [57-85-2] (1) by chloranil gives the corresponding 4,6-diene, [25862-97-9] (2). Conjugate addition of methylmagnesium bromide gives, aftersaponification, 7-alpha-Methyltestosterone (U 14103) [7642-58-2] (3) along with some of the 7β-epimer. Oxidation of the alcohol withpyridinium chlorochromate gives 7alpha-Methylandrost-4ene-3,17-dione, PC23383196 (4). Oxidation with DDQ gives 7alpha-methyl-1,4-androstadiene-3,17-dione, PC54064745 (5). 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 (6). 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 [10448-96-1] (7).
It can also be made from dehydronandrolone acetate.[15] 7a-Methyl-estra-4-en-3,17-dione (Mentabolan) [17000-78-1] is oxidized with a catalytic amount of a copper halide in the presence of oxygen.[16]
The chemical synthesis starting fromtrestolone acetate has been described (but this is old work).[17]
^Krause N, Aksin-Artok Ö (2011). "Copper-Mediated and Copper-Catalyzed Addition and Substitution Reactions of Extended Multiple Bond Systems".PATai's Chemistry of Functional Groups.doi:10.1002/9780470682531.pat0450.ISBN978-0-470-68253-1.
^Morais GR, Yoshioka N, Watanabe M, Mataka S, Oliveira CD, Thiemann T (2006). "C7-Substituted Estranes and Related Steroids".Mini-Reviews in Organic Chemistry.3 (3):229–251.doi:10.2174/1570193X10603030229.ISSN1570-193X.
