Abstract
Cycloadditions of steroidal 14,16-dienes with ketene equivalents were investigated,
as routes to estradiol and estriol analogues. The cycloadduct of 3-methoxyestra-
1,3,5(10), 14,16-pentaen-17-yl acetate and 2-chloroacrylonitrile underwent an
unprecedented tandem rearrangement, on attempted alkaline hydrolysis to the
corresponding ketone. This product, obtained in ca. 90% yield, was formulated as
(161R)-3-methoxy-17-oxo-158,161-cyclo-14,168-ethano-148-estra-1,3,5(10)-triene-16L
carbonitrile. The chemistry of the 16Lcarbonitrile was extensively studied and, in
addition, the derived estradiol analogues were prepared and evaluated for receptorbinding
affinity. The 161-carbonitrile, and its derivatives, could be transformed into
14,15-dihydrocyclobutano or 148,168-bridged compounds by cleavage of a cyclopropyl
bond. Indeed, a 14,15-dihydrocyclobutano estradiol analogue was synthesised and
submitted for biological evaluation.
The cycloadduct of 3-methoxyestra-1,3,5(10),14,16-pentaen-17-yl acetate and 2-
acetoxyacrylonitrile afforded the corresponding 17-hydroxy 16-oxo compound on
alkaline hydrolysis. The 17-hydroxy 16-oxo compound was efficiently converted to the
14a,17a-ethano 15,16-etheno compound by the Shapiro reaction. Reduction of the 17-
hydroxy 16-oxo compound led to the formation of the corresponding 16,17-diols, which
gave the derived 148-compounds on glycol cleavage. Furthermore, under acidic
conditions the 16,17-diols were found to undergo high yield 16(17 -+ l 71)abeo
rearrangements, to afford 14,16-etheno compounds.
GRUNDLER, C (2021). Design And Synthesis Of Ring D Modified Steroidal Hormones. Afribary. Retrieved from https://track.afribary.com/works/design-and-synthesis-of-ring-d-modified-steroidal-hormones
GRUNDLER, CLAUDIA "Design And Synthesis Of Ring D Modified Steroidal Hormones" Afribary. Afribary, 15 May. 2021, https://track.afribary.com/works/design-and-synthesis-of-ring-d-modified-steroidal-hormones. Accessed 24 Nov. 2024.
GRUNDLER, CLAUDIA . "Design And Synthesis Of Ring D Modified Steroidal Hormones". Afribary, Afribary, 15 May. 2021. Web. 24 Nov. 2024. < https://track.afribary.com/works/design-and-synthesis-of-ring-d-modified-steroidal-hormones >.
GRUNDLER, CLAUDIA . "Design And Synthesis Of Ring D Modified Steroidal Hormones" Afribary (2021). Accessed November 24, 2024. https://track.afribary.com/works/design-and-synthesis-of-ring-d-modified-steroidal-hormones