Abstract
Three series of steroid derivatives, enones
1, enols
2 and saturated alcohols
3, were easily synthesized from estrone according to a sequence of three reactions: an aldol condensation with an aromatic aldehyde (R
a–
g
CHO) to afford
1, the carbonyl reduction of
1 to obtain the enol
2, and the double bond reduction of
2 to give
3 with the R
a–
g
group 16β-oriented. All compounds were tested as inhibitors of type 1 17β-HSD. The inhibitory potency increases in the following order
1
<
2
<
3, suggesting that the presence of a flexible 16β-methylene group allows a better positioning of the aryl moiety. With an IC
50 of 0.8
μM, the 16β-benzyl-E
2 (
3a) is the best inhibitor in this series.