Synthesis of deuterium-labelled medroxyprogesterone, megestrol and melengestrol derivatives

The deuterium-labelled medroxyprogesterone derivatives 1 and 2, were prepared by opening of the epoxide in 5β, 6β-epoxy-17α-hydroxypregnane-3,20-dione 3,20-bis(ethyleneketal)(9β) with [2H3]methyl magnesium iodide and further processing of the thus obtained 6-C-pregnane derivative, 10. [2H3]megestrol acetate (4) was prepared by p-chloranil oxidation of [2H3]medroxyprogesterone acetate (2). Subsequent deacetylation of 4 gave [2H3]megestrol (3). In a similar fashion, 16-dehydro-16-methylprogesterone (11) was converted into [2H3]melengestrol (5) and its acetate, 6. In addition, the application of the labelled steroids in the detection of gestagens in samples of kidney fat was shown.