Convenient large scale preparation of catechol estrogens

Stubenrauch, Gerd; Knüppen, R.

doi:10.1016/0039-128x(76)90010-6

Cited by 74 publications

(29 citation statements)

References 26 publications

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“…Following this step, 4-aminoestrone was then converted to 4-hydroxyestrone according the same procedure (Stuenrauch and Knuppen, 1976). Here a few minor modifications are worth noting.…”

Section: Synthesis Of 4-hydroxyestronementioning

confidence: 99%

“…There was obtained (843. The C-4 or?/zo-aminophenol group was further converted to an orr/io-quinone under an inverse oxidation technique as described earlier (Stubenrauch and Knuppen, 1976), and the subsequent reduction of the orf/io-quionone yielded 4-hydroxyestrone.…”

Section: -Aminoestrone Ri35(10)-estratrien-4-ainino-3-oi-17-one; Cmentioning

confidence: 99%

“…4-Nitroestrone was reduced to 4-aminoestrone [l,3,5(10)-estratrien-4-amino-3-ol-17-one] according to the procedure described by Stubenrauch and Knuppen (Stubenrauch and Knuppen, 1976).…”

Section: -Aminoestrone Ri35(10)-estratrien-4-ainino-3-oi-17-one; Cmentioning

confidence: 99%

“…1). 4-OH-E2 was synthesized according to the procedure of Stubenrauch and Knuppen (Stubenrauch and Knuppen, 1976). …”

Section: Chemicalsmentioning

confidence: 99%

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Effects of Nationally-Occurring Estrogen-Fatty Acid Esters on Mammary Cell Growth and Carcinogenesis in Female Rats

Mills¹,

Zhu²

2003

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Wa^ington Headquarters Senrfces, Directorate for Infomiation Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Ariington, VA 22202-4302, and PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)University of South Carolina Research Foundation Columbia, South Carolina 29208 E-Mail: lmills@cop. sc. edu My studies have compared the carcinogenic effects of an Ei-ivp-fatty acid ester preparation, E2 and 4-OH-E2 in the breast, pituitary and uterus of ACI rats. Results showed that chronic administration of an Ea-lVP-fatty acid ester preparation to these rats preferentially induces the development of mammary tumors while chronic administration of E2 results in the preferential formation of pituitary tumors. The chronic administration of 4-OH-E2 to intact female ACI rats did not induce the formation of mammary or pituitary tumors, although there was hyperplasia present in the mammary glands. These results are the first report demonstrating that chronic administration of an estrogen fatty acid ester selectively induces the development of mammary tumors in this animal model. In order to study the carcinogenic activity of other estrogen fatty acid esters, such as those of 4-OH-E2, they must first be synthesized. Therefore, a facile method for the chemical synthesis of large amounts of 4-hydroxyestradiol-17p-stearate, a representative fatty acid ester of the strongly-procarcinogenic estrogen metabolite 4-hydroxyestradiol, has been developed with estrone as the starting material. The ready availability of large amounts of chemically-synthesized 4-hydroxyestradiol-IVP-fatty acid esters make it possible for future studies to systematically characterize their hormonal and carcinogenic potency and efficacy. Appendices 11 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES)U SUBJECT TERMS INTRODUCTIONExogenous administration of estrogens has been shown to induce tumor formation in animals (Nandi et al, 1995;Clifton and Meyer, 1956;Kirkman, 1959;Cutts and Noble, 1964;Newbold et al, 1990; and Li and Li, 1996). In humans, there is strong evidence showing that chronic estrogen administration more readily correlates with an increase in uterine cancer risk than breast cancer risk (Ziel and Finkle, 1975; Sitteri, et al., 1976;. Although the difference is not fully understood, it is possible that some of the biologically active estrogen derivatives, such the estrogen fatty acid esters, may play a more significant role than estradiol-17|32 in the induction of breast cancer.Recently it was suggested that the mammary adipocytes may serve as a storage site for the lipoidal estrogen fatty acid este...

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“…Following this step, 4-aminoestrone was then converted to 4-hydroxyestrone according the same procedure (Stuenrauch and Knuppen, 1976). Here a few minor modifications are worth noting.…”

Section: Synthesis Of 4-hydroxyestronementioning

confidence: 99%

Section: -Aminoestrone Ri35(10)-estratrien-4-ainino-3-oi-17-one; Cmentioning

confidence: 99%

“…4-Nitroestrone was reduced to 4-aminoestrone [l,3,5(10)-estratrien-4-amino-3-ol-17-one] according to the procedure described by Stubenrauch and Knuppen (Stubenrauch and Knuppen, 1976).…”

Section: -Aminoestrone Ri35(10)-estratrien-4-ainino-3-oi-17-one; Cmentioning

confidence: 99%

“…1). 4-OH-E2 was synthesized according to the procedure of Stubenrauch and Knuppen (Stubenrauch and Knuppen, 1976). …”

Section: Chemicalsmentioning

confidence: 99%

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Effects of Nationally-Occurring Estrogen-Fatty Acid Esters on Mammary Cell Growth and Carcinogenesis in Female Rats

Mills¹,

Zhu²

2003

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“…The extracts obtained from rat hepatocyte incubations have been directly analysed by LC-MS/MS using ESI and APCI ionisation techniques, which proved to be very complementary for the determination of polar as well as non-polar metabolites. [4,5,6,7]. HPLC grade solvents from Scharlau (Scharlau, Barcelona, Spain) and water from a Milli-Q system (Millipore, Saint-Quentin-en-Yveline, France) were used for LC-MS analyses.…”

mentioning

confidence: 99%

Investigation of the in vitro metabolism of 17b-estradiol by LC-MS/MS using ESI and APC

Rathahao¹,

Hillenweck²,

Paris³

et al. 2000

Analusis

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The steroid hormone estradiol is mainly metabolised (i) by oxidation of the hydroxyl function at the C17 position via steroid dehydrogenase, leading to estrone, and (ii) by hydroxylation via cytochrome P450 enzymes, occurring on the preferred positions C16α, C2 and C4 of the steroid (Fig. 1). When the hydroxylation takes place on the aromatic A ring of the steroid (positions 2 and 4), it leads to the formation of catechol-estrogens [1]. These compounds undergo several enzymatic processes to be either converted into inactive O-methoxylated metabolites or oxidised into quinone forms. Due to their highly electrophilic properties, estrogen quinones are extremely reactive species. Although they can be inactivated by conjugation with glutathione [2], they are also likely to react with DNA bases to form covalent adducts. This process can induce mutagenicity phenomenons [3], and is known to constitute a critical first step in several tumor initiation processes.The aim of this work was to study the in vitro metabolism of 17β-estradiol using hepatocytes in order to assess the formation of catechol estrogens at the cellular level. Thus, the detection of the catechol estrogens and their subsequent biotransformation products, i.e. glucuronide or glutathione conjugates and O-methoxylated derivatives, has been particularly emphazised. The extracts obtained from rat hepatocyte incubations have been directly analysed by LC-MS/MS using ESI and APCI ionisation techniques, which proved to be very complementary for the determination of polar as well as non-polar metabolites. [4,5,6,7]. HPLC grade solvents from Scharlau (Scharlau, Barcelona, Spain) and water from a Milli-Q system (Millipore, Saint-Quentin-en-Yveline, France) were used for LC-MS analyses. Material and methods Chemicals Cell preparationHepatocytes were prepared from Wistar rat livers according to the method described by Seglen * Corresponding authorLiquid chromatography coupled to tandem mass spectrometry with electrospray ionisation (ESI) and atmospheric pressure chemical ionisation (APCI) were used for the investigation of the in vitro metabolism of 17β-estradiol on rat isolated hepatocytes. The catechol estrogens corresponding to 17β-estradiol and estrone were identified by ESI, together with their glutathione and glucuronide conjugates, whereas more apolar compounds such as methoxylated catechol estrogens were characterised using APCI.

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Preparation of Difunctional Compounds

1978

Compendium of Organic Synthetic Methods

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Convenient large scale preparation of catechol estrogens

Cited by 74 publications

References 26 publications

Effects of Nationally-Occurring Estrogen-Fatty Acid Esters on Mammary Cell Growth and Carcinogenesis in Female Rats

Effects of Nationally-Occurring Estrogen-Fatty Acid Esters on Mammary Cell Growth and Carcinogenesis in Female Rats

Investigation of the in vitro metabolism of 17b-estradiol by LC-MS/MS using ESI and APC

Preparation of Difunctional Compounds

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