合成路线1

The reaction of cyanohydrineketal (I) with dimethyl(chloromethyl)silyl chloride (A), TEA and DMAP in THF gives the silylated cyanohydrine (II), which is treated with Li and 4,4'-di-tert-butylbiphenyl (DBB) in THF followed by acidification with HCl yields 17alpha-hydroxy-19-norpregna-4,9-diene-3,20-dione (III). The reaction of (III) with ethylene-glycol and TsOH afford the bis ethylenedioxy derivative (IV), which is epoxidized with H2O2 and trifluoroacetone in dichloromethane affording the monoepoxide (V). The Grignard condensation of (V) with 4-(dimethylamino)phenylmagnesium bromide in THF provides the 11-beta-(dimethylamino) derivative (VII), which is dehydrated and deprotected with sulfuric acid in refluxing ethanol to furnish 11-beta-[4-(dimethylamino)phenyl]-17alpha-hydroxy-19-norpregna-4,9-diene-3,20-dione (VIII). Finally, this compound is acetylated with AcOH and trifluoroacetic anhydride in dichloromethane.

合成路线2

Protection of cyanohydrin ketal (I) with bromomethyldimethylsilyl chloride (A) in presence of DMAP and Et3N affords derivative (II), which is converted into (III) by means of LDA in cyclohexane and aqueous HBr. Treatment of (III) with KOAc in acetone yields acetoxy derivative (IV), which is then hydrolyzed to provide (V) by means of KHCO3 in refluxing MeOH. Protection of (V) as its acetal form by treatment with ethylene glycol in p-TsOH affords (VI), which is converted into methyl ether (VII) by treatment with Me3O+BF4- in presence of 1,8-bis(dimethylamino)-naphthalene. Oxidation of (VII) by means of H2O2, Na2HPO4 and (CF3)2CO in CH2Cl2 yields epoxide (VIII), which is converted into (X) by a Grignard reaction with (IX) in THF followed by treatment with CuCl. Diketal (X) is then deprotected by means of TFA in THF to provide derivative (XI), which is finally acetylated with (CF3CO)2O in a mixture of HOAc, p-TsOH and CH2Cl2.

合成路线3

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合成路线5