A simple chemical method for the synthesis of catechol estrogens

Gelbke, H; Haupt, Otto; Knüppen, R.

doi:10.1016/s0039-128x(73)80005-4

Cited by 73 publications

(14 citation statements)

References 22 publications

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“…Briefly, the 2-hydroxy derivatives of the deuterated compounds were prepared according to the method described by Gelbke et al [36]. The deuterated quinones were prepared by oxidation in acetonitrile at Ϫ40°C of the corresponding catechols using activated manganese dioxide utilizing a procedure published by Abul-Hajj et al [37].…”

Section: Methodsmentioning

confidence: 99%

Investigation of the regio- and stereo-selectivity of deoxyguanosine linkage to deuterated 2-hydroxyestradiol by using liquid chromatography/ESI-ion trap mass spectrometry

Debrauwer

Rathahao

Jouanin

et al. 2003

J. Am. Soc. Mass Spectrom.

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From previous studies on the reactivity of estradiol 2,3-quinone towards deoxyribonucleosides, it was demonstrated that several isomeric adducts were formed. Although adduction on steroid ring A or B has been evidenced using sequential MS n experiments, in some cases attachment positions are difficult to identify unambiguously. In this work, 2-hydroxyestradiol labeled with deuterium at various positions [6␤ (1); 6␣-7␣ (2); 6␣-6␤-7␣ (3)] have been used. Isomeric adduct differentiation could be achieved using LC-ESI-MS n . The m/z shift of the quasi-molecular ions as well as the fragmentation pathways suggested that adduction could occur on both C6 and C9 sites of the steroid B ring: Nucleophilic attack of the base on the C6 position of the steroid led to major adducts and addition of the base on the activated C9 site gave minor adducts that were found to be unstable. LC-MS n experiments carried out under deuterated medium provided information about some fragmentation processes by studying the m/z shift of fragment ions: (1) the loss of deoxyribose from the quasi-molecular ions took place according to a process involving a deuterium transfer from the deoxyribose alcohol function; (2) the cleavage of the steroid-base linkage involved a deuterium transfer from the hydroxy group of the catechol and likely occurred via the formation of an ion-dipole complex. The model studies conducted in this work provide new information on the fragmentation mechanisms of covalent adducts formed from estrogen quinones and deoxyguanosine, the most reactive DNA base. Besides, the first unequivocal characterization of adducts involving the steroid C9 position is shown by using deuterium labeled estrogen quinones. (J Am Soc Mass Spectrom 2003, 14, 364 -372)

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Section: Methodsmentioning

confidence: 99%

Investigation of the regio- and stereo-selectivity of deoxyguanosine linkage to deuterated 2-hydroxyestradiol by using liquid chromatography/ESI-ion trap mass spectrometry

Debrauwer

Rathahao

Jouanin

et al. 2003

J. Am. Soc. Mass Spectrom.

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“…[6,7-3H]2-hydroxyoestradiol and [6,7-3H]2-hydroxyoestrone was synthesized from [6,7-3H]oestradiol and [6,7-3H]oestrone, respectively (50 Ci/mMole, New England Nuclear Co., Boston, USA) according to Gelbke et al (1973). The radioactive compounds were stored in etha¬ nol containing 0.1 % ascorbic acid (w/v) at 4°C.…”

Section: Steroidsmentioning

confidence: 99%

Concentrations of 2-hydroxyoestrogens in human sera measured by a heterologous immunoassay with an 125I-labelled ligand

Berg

Thaler

Kuß

1982

Acta Endocrinologica

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A heterologous immunoassay for 2-hydroxyoestrogens1 has been established in which antibodies raised against 2-hydroxyoestradiol-17-succinyl-BSA serve as binding protein and 2-hydroxyoestrone-17-cmo\x=req-\[125I]iodohistamine as radioligand. Lipophilic serum components competing for binding sites in this system were defined as 'total 2-hydroxyoestrogens'. The underlying assumption of specificity was supported by the pattern of cross-reactivity evaluated with structural related steroids and o-diphenols and by the fact, that an additional chromatography of the serum extracts preceding the competing reaction had little if any effect. Sensitivity: 2.8 \m=+-\1 pg/tube; accuracy: Y = 0.91x + 2.2; r = 0.989; precision: 5.8% intra-assay; 6.5% inter-assay. The following concentrations ( \ m=+-\ standard deviation) were found in the sera of healthy subjects.Young men: 29 \m=+-\5 pg/ml (n = 11); women follicular phase: 32 \m=+-\8 pg/ml (n = 25); luteal phase: 53 \m=+-\13 pg/ml (n = 23); postmenopausal women: 13 \m=+-\4 pg/ml (n = 10); pregnant women 11th\p=n-\20th week: 70 \m=+-\16 mg/ml (n = 64); 36th\p=n-\40thweek: 240 \m=+-\23 pg/ml (n = 40); newborn cord blood: 604 \m=+-\43 pg/ml (n = 48).2-Hydroxyoestrogens have been recognized as major metabolites of oestrone and oestradiol in both laboratory animals and humans. The opinions on their physiological significance are still at vari¬ ance (Ball & Knuppen 1980). The assay of cate¬ choloestrogens in biological fluids and tissue by the classical methods of steroid separation and detec¬ tion is hampered by their chemical instability. They are highly susceptible to attack by oxidants, especi¬ ally in alcaline media. In addition, the classical methods are time consuming, expensive and not applicable for routing determinations. These pro¬ blems have been mastered by the development of suitable radioimmunoassays (Chattoraj et al. 1978;Ball et al. 1978). Methods currently available utilise tritium labelled radioligands, which are not avail¬ able commercially. Their syntheses are lengthy and tedious with generally small yields. In establishing a sensitive and specific radioimmunoassay of serum catecholestrogens we preferred the use of 125I-labelled radioligands, which offer the advan¬ tages of higher specific activities and cost-saving counting for at least 3 months after preparation. In order to obtain a very high sensitivity of the assay we utilized a heterologous bridge system employing anti-2-hydroxyoestradiol-17ß-succinyl-BSA-serum and 2-hydroxyoestrone-17-cmo-[125I]-iodohistamine. Preliminary results have been pub¬ lished previously (Berg et al. 1981).1 The following trivial names and abbreviations were used: 2-hydroxyoestrone = 2,3-dihydroxy-l,3,5(10)-oestratrien-17-one, 2-hydroxyoestradiol = l,3,5(10)-oestratriene-2,3,17ß-triol, 2-hydroxyoestriol = l,3,5(10)-oestratriene-2,3,16a,17ß-tetrol, oestradiol-17ß = 1,3,5(10)-oestratriene-3,17ß-diol, oestrone = 3-hydroxy-1,3,5(10)-oestratrien-17-one, oestriol = l,3,5(10)-oestratriene-3-16a, 17ß-triol, 2-methoxyoestrone = 2-methoxy-3-h...

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“…The final radiochemical purity was more than 96%. 4-OHOe2 and 4-OHOej were obtained by oxidation of oestradiol and oestrone with Fremy's salt (Gelbke et al 1973). The 4-monomethyl ether of 4-OHOe2 was prepared by enzymatic methylation of 4-hydroxyoestradiol using S-adenosylmethionine (Boehringer, Mannheim, Germany) and subsequently purified by paper chromatography (PC I).…”

Section: Steroids and Chemicalsmentioning

confidence: 99%

Comparative Studies on the Metabolism of Oestradiol in the Brain, the Pituitary and the Liver of the Rat

Ball

Haupt

Knüppen

1978

Acta Endocrinologica

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Radioactive oestradiol was incubated with homogenates of hypothalamus, pituitary and liver and slices of cortex, hippocampus, hypothalamus, pituitary and liver of ovariectomized rats. 2-and 4-substituted oestrogens were the main metabolites in the brain and were found in the same proportions.In the liver only the 2-substituted oestrogens were the main metabolites, while the 4-substituted ones were of minor quantitative importance. On the basis of wet weight the 2-hydroxylating capacity of the liver was approximately 50 fold greater than that of the brain and the 4-hydroxylating capacity about the same as that of the brain. Only slight differences in the 2-and 4-hydroxylating capacity of various brain areas were observed, although apparently the hypothalamus and the pituitary were more active in the formation of catecholoestrogens than the cortex and the hippocampus.The importance of oestradiol in the control of the hypothalamic-pituitary function is well established (Vande Wiele et al. 1970; Young 8c Jaffe 1976).A recent report concerning the participation of catecholamines in this process (Kamberi 1974) and our findings dealing with the competitive interaction of catecholamines and catecholoestrogens via the catechol O-methyltransferase

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A simple chemical method for the synthesis of catechol estrogens

Cited by 73 publications

References 22 publications

Investigation of the regio- and stereo-selectivity of deoxyguanosine linkage to deuterated 2-hydroxyestradiol by using liquid chromatography/ESI-ion trap mass spectrometry

Investigation of the regio- and stereo-selectivity of deoxyguanosine linkage to deuterated 2-hydroxyestradiol by using liquid chromatography/ESI-ion trap mass spectrometry

Concentrations of 2-hydroxyoestrogens in human sera measured by a heterologous immunoassay with an 125I-labelled ligand

Comparative Studies on the Metabolism of Oestradiol in the Brain, the Pituitary and the Liver of the Rat

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