Manufacturing Process
To solution of 6α-methyl-4-pregnen-17α-ol-3,20-dione (1.0 g) in ethane-dithiol (1 ml) and methylene chloride (2 ml) pyridine chlorhydrate (1 g) was
added and mixed 3 min at room temperature. Then to reaction mixture
methanol (30 ml) was added and cooled in ice bath during of 2 min.
Precipitate was filtered and washed with cool methanol. 6α-Methyl-4-pregnen-
17α-ol-20-one-3-thioacetal was obtained (0.9 g), melting point 186°-188°C
(recrystalisation from methanol-dichlormethane).
To the solution of 6α-methyl-4-pregnen-17α-ol-20-one-3-thioacetal (2 g) in
95% ethanol (200 ml) Ni (Renney) (50 g) was added and mixed at heating.
Then reaction mixture was cooled to room temperature. The mixture was
filtered, and filtrate was evaporated, obtaining residue was crystallisated from
methanol with dichloromethane and in the result 6α-methyl-4-pregnen-17α-
ol-20-one (0.95 g) was produced, melting point 190°-193°C.
To the solution of 6α-methyl-4-pregnen-17α-ol-20-one (1.5 g) in acetic acid
(75 ml) and acetic anhydride (15 ml) p-toluenesulfonic acid was added and
the reaction mixture allayed to stand at room temperature any time. Then
crystals were recrystallised from methanol with dichlormethane. Acetate 6α-
methyl-4-pregnen-17α-ol-20-one (1.3 g) was obtained, melting point 173°-
175°C.
World Health Organization (WHO)
Anagestone acetate, a synthetic progestogen, was introduced in
1968 as a component in oral contraceptive preparations. In 1969, it was shown to
be associated with an increased risk of mammary tumours in dogs which led the
United States Food and Drug Administration to order the termination of its use in
all clinical trials. Subsequently the manufacturer withdrew preparations containing
anagestone acetate, ultimately on a worldwide basis.
