Synthesis of deuterium-labelled medroxyprogesterone, megestrol and melengestrol derivatives

Abstract

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.