The bromination of 17-beta-hydroxy-17-alpha-methyl-5-alpha-androstan-3-one (I) with Me3NPhBr3 or PyrBr3 gives the 2-bromo derivative (II), which is dehydrobrominated by means of LiBr or MgBr2 and Li2CO3 in hot DMF to yield 17-beta-hydroxy-17-alpha-methyl-5-alpha-1-androsten-3-one (III). The ozonolysis of (III) with ozone and NaOH in methanol affords the seco intermediate (IV), which is finally reductocyclized by means of NaBH4 and NaOH in methanol to provide the target oxa-androstane derivative.
The reaction of the secoandrostane dicarboxylic acid (I) with acetic anhydride, propionic anhydride or DCC in THF gives the corresponding anhydride (II), which is reduced with NaBH4, LiAlH4, LiAlH(t-BuO)3 or LiBHEt3 in DMF or THF to afford the target 2-oxaandrostane derivative. Alternatively, this synthesis can also be performed in a one pot reaction. Reaction of the seco diacid (I) with acetic or propionic anhydrides and further reduction with NaBH4 yields the target 2-oxaandrostane derivative, without isolation of the intermediate anhydride.
The bromination of 17beta-hydroxy-17alpha-methyl-5alpha-androstan-3-one (I) with Br2 in DMF gives the 2-bromo derivative (II), which is treated with LiCl and Li2CO3 in refluxing DMF to yield 17beta-hydroxy-17alpha-methyl-5alpha-androst-1-en-3-one (III) (1). The oxidative cleavage of (III) by means of Pb(OAc)4 and OsO4 in AcOH affords the seco steroid (IV), which is finally submitted to a reductive cyclization by means of NaBH4 and NaOH in water to provide the target 2-oxa steroid (1-3).