Photocyclization of diethylstilbestrol. Isolation of a stable, self-trapping dihydrophenanthrene intermediate

Doyle, Thomas D.; Benson, Walter R.; Filipescu, Nicolae

doi:10.1021/ja00427a035

Cited by 32 publications

(20 citation statements)

References 6 publications

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“…DES-phenanthrene arises from photocyclization of cis-DES (20). This process is not unlike that seen for vitamin D3 produced by UV irradiation in the skin from relatively inactive 7-dehydrocholesterol (21).…”

Section: Discussionmentioning

confidence: 98%

Estrogenic activity in vivo and in vitro of some diethylstilbestrol metabolites and analogs

Korach

Metzler

McLachlan

1978

Proc. Natl. Acad. Sci. U.S.A.

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The diethylstilbestrol (DES) metabolite (8-dienestrol), which had been identified in mouse, rat, monkey, and human urine, and two proposed metabolic intermediates (diethylstilbestrol a,a'-epqxide and a,a'-dihydroxy DES) were synthesized and their estrogenic activities determined. In addition, three DES analogs, a-dienestrol, DES-dihydroxy diethyl phenanthrene (DES-phenanthrene), and 14a-ethyl, 4a-hydroxyphenyl)indanyl-5-ol (indanyl-DES), were studied. Estrogenic activities of the compounds in vivo were determined by the immature mouse uterine weight bioassay; in vitro, their estradiol receptor binding activity (competitive equilibrium binding, sucrose gradient analysis, and association rate inhibition assays) was determined. Results of the mouse uterine weight bioassay gave the following order of estrogenicity: DES > a-dienestrol Diethylstilbestrol (DES) is a nonsteroidal estrogen first synthesized and described by Dodds in 1938 (1). It has significant oral activity as an estrogenic substance and invokes a strong hormonal response equivalent to an injected dose of the steroidal estradiol-17fl.In recent years, reports by Herbst and colleagues (2) have linked in utero exposure to DES with subsequent developmernt of vaginal clear cell adenocarcinoma in a number of female offspring. A detailed review by Gunning of the human studies has been published (3). Investigations in our laboratory (4, 5) have been concerned with the development of an animal model system for studying this effect of in utero exposure.Pharmacokinetic studies with radiolabeled DES in the laboratory mouse model (6) have shown that this compound is localized in the fetal reproductive tract and associated struc-

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Section: Discussionmentioning

confidence: 98%

Estrogenic activity in vivo and in vitro of some diethylstilbestrol metabolites and analogs

Korach

Metzler

McLachlan

1978

Proc. Natl. Acad. Sci. U.S.A.

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“…This intermediate has been isolated for diethylstilbestrol. 15 This step, followed by removal of hydrogen atoms by dissolved molecular oxygen (or other hydrogen acceptors which might be present in the system), yields the phenanthrene derivative. This transformation is generally fairly rapid and, as mentioned, has served as the basis for post-column derivatization in the quantitation of tamoxifen and its derivatives in biological matrices.…”

Section: Identi®cation Of Acidic Decay Products 6 Andmentioning

confidence: 99%

Identification of photodegradants of droloxifene by combined HPLC--MS, NMR spectroscopy and computational chemistry

Campeta

Lombardo

Sharp

et al. 1999

J. Phys. Org. Chem.

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A combination of high-performance liquid chromatography (HPLC)-mass spectrometry and 1 H and 13 C NMR spectroscopy was utilized to characterize the photodecay products of droloxifene, a potent new estrogen receptor agonist. Structurally similar to tamoxifen, droloxifene demonstrates a complex and unique decay scheme, including the formation of two naphthalene derivatives which were unexpected decay products and previously unreported for this class of compound. Elucidation of the decay products was assisted by the use of computational chemistry, namely by correlating simulated UV spectra and aqueous solvation free energies with actual UV spectra and HPLC retention data. In addition to describing the photodecay scheme of droloxifene, the present work demonstrates the utility of computational chemistry in providing support for the identification of unknown compounds.

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“…Die Reaktion kann nicht mit dem Triplettquencher trans-1,3-Pentadien abgebrochen werden. [8] Sowohl mit Substraten, die stark elektronenziehende Substituenten tragen (9, 10), als auch mit solchen mit stark elektronenschiebenden (11) photochemischen konrotatorischen Sechs-Elektronen-Photocyclisierung zum trans-verknüpften Dihydrophenanthren-Zwischenprodukt [10] DP1 reagieren. Eine anschlieûende [1,9]-H-Verschiebung liefert das Dihydrophenanthren DP2.…”

unclassified

“…Versuche zur Isolierung der Zwischenprodukte DP1 und DP2 waren erfolglos, wenngleich es Beispiele für den erfolgreichen Abfang des Dihydrophenanthren-Zwischenprodukts gibt. [10] Ein Beispiel [11] für die analoge Umwandlung eines entsprechenden Dihydronaphthalins ist die von 21 in der thermischen Reaktion von trans-9,10-Dihydronaphthalin 20 zu cis-1-Phenylbuta-1,3-dien 22 [Gl.…”

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Eine neuartige photochemische Umlagerung von Styrylfuranen

Wang

1999

Angewandte Chemie

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Photocyclization of diethylstilbestrol. Isolation of a stable, self-trapping dihydrophenanthrene intermediate

Cited by 32 publications

References 6 publications

Estrogenic activity in vivo and in vitro of some diethylstilbestrol metabolites and analogs

Estrogenic activity in vivo and in vitro of some diethylstilbestrol metabolites and analogs

Identification of photodegradants of droloxifene by combined HPLC--MS, NMR spectroscopy and computational chemistry

Eine neuartige photochemische Umlagerung von Styrylfuranen

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