The regio- and stereo-selective reduction of steroidal 4-en-3-ones using Na_2S_2O_4/NaHCO_3 and CuCl/NaBH_4

摘要

This paper describes the regio- and stereoselective reduction of DELTA~4-3-keto moiety in certain steroids using Na_2S_2O_4/NaHCO_3 and CuCl/NaBH_4) respectively. Using either one of the two reduction agents in the reaction, the 17-substituents in the D ring were observed to have clearly influenced the stereoselective reduction of 4-ene in the A ring by the so-called conformational transmission effect. Na_2S_2O_4/ NaHCO_3 regioselectively reduced C=C at 4-position of 17-substituted-androst-4-en-3-one derivatives to 5alpha-H-3-one as the main isomer. And as an extended application, Epiandrosterone (11) was further synthesized from androst-4-en-3,17-dione (AD) via four steps. The total yield from this was about 45. In the presence of CuCl/NaBH_4, DELTA~4-3-keto conjugated reduction of 17-spirocyclic ethylene ketal protected androst-4-en-3-one derivatives mainly produced 3alpha-hydroxy-5beta-H isomers, at a yield around 81. Considering the scaffold configuration of 3alpha-hydroxy-5beta-H moiety coincided with that of bile acid analogs, this selective reduction could also be used as an alternative method for the synthetic study of bile acids using AD and its derivatives, which are from the microorganism degradation of natural sterols, as the potential materials. Meanwhile, configurations of the reductive compounds 5b, 6b, 9,10 and 17e were identified by X-ray diffraction.