2004 Volume 52 Issue 6 Pages 722-726
To study the stereochemical aspects of the aromatase reaction of androst-4-en-17-one (1) and its 5-ene isomer 4, competitive inhibitors of aromatase, the [19S-3H]- and [19R-3H]-labeled 19-hydroxy derivatives 2 and 5, were synthesized through NaB3H4 reduction of the corresponding 19-aldehydes 3 and 6 as a key reaction. The hitherto unknown stereochemistry of the NaB3H4 reduction was established based on the deuterium-labeling experiments with NaB2H4. A comparison of 1H-NMR spectra of the NaB2H4 reduction products of 19-als 3 and 6 with those of the respective authentic steroids revealed that the ratios of 19S-2H to 19R-2H were 90 : 10 for the 4-ene steroid 2 and 70 : 30 for the 5-ene isomer 5, respectively. Jones oxidation of the [19S-2H]19-ols, followed by the non-labeled NaBH4 reduction, gave the corresponding [19R-2H]19-ols 2 and 5 (R-2H : S-2H=90 : 10 for steroid 2 and 70 : 30 for steroid 5). The stereoselectively 3H-labeled compounds 2 and 5 were similarly obtained in these sequences.