Design and synthesis of ring D modified steroidal hormones
type: CreativeWork
description: 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-15β,16¹-cyclo-14,16β-ethano-14β-estra-1,3,5(10)-triene-16¹-carbonitrile. The chemistry of the 16¹-carbonitrile 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 14β,16β-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 14α,17α-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 14β-compounds on glycol cleavage. Furthermore, under acidic conditions the 16,17-diols were found to undergo high yield 16(17 --> l7¹)abeo rearrangements, to afford 14,16-etheno compounds.
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-15β,16¹-cyclo-14,16β-ethano-14β-estra-1,3,5(10)-triene-16¹-carbonitrile. The chemistry of the 16¹-carbonitrile 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 14β,16β-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 14α,17α-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 14β-compounds on glycol cleavage. Furthermore, under acidic conditions the 16,17-diols were found to undergo high yield 16(17 --> l7¹)abeo rearrangements, to afford 14,16-etheno compounds.
author: Grundler, Claudia
language: eng
date published: 1992
date modified: 2026-07-22T22:23:01Z
provider: University of Cape Town
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Department of Chemistry

PropertyValue
property ID: Handle
value: http://hdl.handle.net/11427/17372