Corrigendum to “Deconstructing estradiol: Removal of B-ring generates compounds which are potent and subtype-selective estrogen receptor agonists” [Bioorg. Med. Chem. Lett. 19 (2009) 1250–1253]

The A-CD analogue of 16β,17α-estriol is a potent and highly selective estrogen receptor β agonist

“…The following routes were used in the synthesis of the estrogen analogues: for the estradiol analogue, the method of Katzenellenbogen and co-workers was followed (Scheme 1). 1,13 Compound 5 was reacted with tert-butyldimethylsilyl-(TBDMS) protected bromophenol and n-butyl lithium leading to the formation of compound 6. Elimination of the tertiary alcohol using a catalytic amount of p-TsOH gave the desired product 7 as an olenic mixture in 19% yield.…”

“…While estriol, 17-epiestriol and 16-epiestriol all showed considerable uterus growth comparable with 17b-estradiol, 16,17-epiestriol showed an effect comparable with the vehicle-treated controls. 12 Recently, it has been shown 1,13 that in A-CD estrogens (Fig. 1) the active isomer is always the one with the 5(S)-stereochemistry and that they generally have a higher ERb selectivity compared to the steroid-based ones.…”

New analogs of steroid estrogens

“…It was established applying the NMR spectroscopy that 7α-methyl-3-methoxy-D-homo-6-oxa-8α,14β-estra-1,3,5(10)-trien-17a-one existed in solution in two conformations distinguished by the structure of the rings B, C, and D simultaneously. The reaction of 17-methylidene-3-methoxy-6-oxa-8α-estra-1,3,5(10)-triene with hydrobromic acid in acetic acid promotes a rearrangement with the migration of a methyl group into the position 17 resulting in the formation of 17,17-dimethyl-6-oxa-8α-gona-1,3,5(10),13(14)-tetraene derivatives.The study of the mechanism of the action of steroid estrogens mediated by their nuclear receptors made it possible to reveal numerous relations between the structure and the biologic properties of this hormone group [1][2][3][4][5], in particular, in the series of estrogens 8α-analogs [6-10]. The formation of an "active" complex between the estrogen α-receptor and the ligands of steroid character requires a precise orientation of the oxygen-containing substituents in the A and D rings with respect to the clusters Glu-353-Arg-394-water and His-524 respectively [11].…”

“…The study of the mechanism of the action of steroid estrogens mediated by their nuclear receptors made it possible to reveal numerous relations between the structure and the biologic properties of this hormone group [1][2][3][4][5], in particular, in the series of estrogens 8α-analogs [6][7][8][9][10]. The formation of an "active" complex between the estrogen α-receptor and the ligands of steroid character requires a precise orientation of the oxygen-containing substituents in the A and D rings with respect to the clusters Glu-353-Arg-394-water and His-524 respectively [11].…”