SYNTHESIS OF DEUTERIUM-LABELED MEDROXYPROGESTERONE, MEGESTROL AND MELENGESTROL DERIVATIVES

The deuterium-labelled medroxyprogesterone derivatives 1 and 2, were p repared by opening of the epoxide in 5 beta,6 beta-epoxy-17 alpha-hydr oxypregnane-3,20-dione 3,20-bis(ethyleneketal) (9 beta) with [H-2(3)]m ethyl magnesium iodide and further processing of the thus obtained 6-C -pregnane derivative, 10. [H-2(3)]megestrol acetate (4) was prepared b y p-chloranil oxidation of [H-2(3)]medroxyprogesterone acetate (2). Su bsequent deacetylation of 4 gave [H-2(3)]megestrol (3). In a similar f ashion, 16-dehydro-16-methylprogesterone (11) was converted into [H-2( 3)]melengestrol (5) and its acetate, 6. In addition, the application o f the labelled steroids in the detection of gestagens in samples of ki dney fat was shown.