Design and Synthesis of Two BICYCLO[3.3.1]NONANE-STEROID Derivatives (original) (raw)
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Chemistry of Heterocyclic Compounds, 2009
Methyl-substituted 6-oxa-8α-analogs of steroid estrogens have been synthesized and the 1 H and 13 C NMR signals of these compounds have been completely assigned. It is shown that introduction of a methyl group in position 4 of steroids of the given stereochemical series leads to the loss of uterotropic and hypertriglyceridemic effects of the modified compounds. Steroids with these properties may have promise for the creation of vectors for transport into target organs of estrogens of other classes of compounds and inhibitors of enzymes responsible for the metabolism of hormones.
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The Synthesis and Properties of B Nor8-Isoanalogues of Steroid Estrogens
Russian Journal of Bioorganic Chemistry
The study of the binding of estradiol B-nor-8-isonalogues to estrogen receptors from the rat uterus helped create the proposed model of the corresponding ligand–receptor complexes. The use of this model ensured the choice of such micromodifications in this steroid group that sharply decreased their hormonal activity. By the example of 16,16-dimethyl-D-homo-B-nor-8-isoestrone, we demonstrated the possibility of the synthesis of the estrogen analogues devoid of uterotropic activity but retaining immunosuppressive activity.
Russian Journal of General Chemistry, 2011
The interproton distances in the molecule of 17aβ-acetoxy-16,16-dimethyl-3-methoxy-D-homo-Bnor-9β-estra-1,3,5(10)-triene, determined from the X-ray diffraction data and by 1 H NMR spectroscopy, were consistent with those calculated ab initio and by the PM3 and MM+ methods. Therefore, MM+ calculations were used to perform docking of a series of D-homo-B-nor-9β-estra-1,3,5(10)-trienes to hormone-binding pocket of estrogen α-receptors, and 16,16-dimethyl-D-homo-B-nor-9-estrone was selected for studying its biological properties. This compound was found to possess cardioprotective activity and no uterotropic effect. 9β-Analogs of steroidal estrogens are characterized by modified spectrum of biological activity as compared to the corresponding natural compounds [1-3]; they are also used as intermediate products in the synthesis of 9β,10α-androgen [4] and 9β,10αprogestagen derivatives [5]. Biological properties of Bnor-9β-estrogens are almost unknown. 18-Methyl-Dhomo-B-nor-9β-estrone was reported to exhibit antiatherosclerotic effect, whereas its uterotropic activity was completely absent [6, 7]. The latter is very important, for in most cases hormone action of estrogens is related to their cancerogenic effect [8].
Oriental Journal of Chemistry
Several bicycle-derivatives have been prepared using different protocols; nevertheless, expensive reagents and special conditions are required. The aim of this study was synthesize a dioxa-diazaspiro[bicyclo[9.4.2]heptadecane-steroid-dienyne derivative by a series of reactions which involving; a) alkinilization of estrone or OTBS-estrone with 5-hexyn-1-ol to form two propargyl alcohol derivatives (3 or 4); b) esterification 3 or 4 with succinic acid to form two dioxaspiro-steroidcyclotridecan derivatives (5 or 6); c) preparation of diazaspiro[bicycle[9.4.2]heptadecane-steroid-4 amino complex (7 or 8) by reaction of 5 or 6 with ethylenediamine; d) removal of silyl fragment of 8 via hydrofluoric acid to form the compound diazaspiro[bicycle[9.4.2] heptadecane-steroid-3´-ol (9); e) preparation of diazaspiro[bicycle[9.4.2]heptadecane-steroid-4-oxobutanoic acid (10) via esterification of 9 with succinic acid; f) amidation of 10 with ethylenediamine to form diazaspiro[bicyclo[9.4.2] heptadecane-steroid-4-aminobutanoate (11); g) synthesis of dioxadiazaspiro [bicyclo[9.4.2] heptadecane-steroid-dienyne (12) via pyrrolization of 11 using boric acid. The chemical structure of compounds was confirmed by NMR spectroscopic data.