[Simple synthesis of a complete set of unconjugated norethisterone metabolites and their deutero-analogs]

Abstract

The short-step synthesis of all norethisterone (NET) hydrogenated metabolites and their deuteroanalogues has been accomplished. Reduction of NET by NaBH4 in the presence of N,N,N',N'-tetramethylethylenediamine provided 19-norpregn-20-yn-3,17-diols as a mixture of 3- and 5-epimers. The individual isomers were isolated by flash chromatography and oxidyzed by PyHCrO3Cl into 5 alpha- and 5 beta-dihydro-NET. These products were converted, on isotopic exchange with D2O--MeOD in alcaline conditions followed by reduction with NaBD4, into four stereoisomeric 2,2,3,4,4-pentadeuterated 19-norpregn-20-yn-3,17-diols; two isomeric 2,2,3,4,4,16,16,17-octadeuterated estrane-3,17-diols were also isolated as side products. All compounds obtained will be used as internal standards for chromato-mass-fragmentographic analysis.