hexestrol-3',4'-quinone | 857837-21-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: hexestrol-3',4'-quinone
• 英文别名: 4-[4-(4-Hydroxyphenyl)hexan-3-yl]cyclohexa-3,5-diene-1,2-dione；4-[4-(4-hydroxyphenyl)hexan-3-yl]cyclohexa-3,5-diene-1,2-dione
• CAS: 857837-21-9
• 化学式: C₁₈H₂₀O₃
• 分子量: 284.355
• InChiKey: WHMZTZNMIAVTOD-UHFFFAOYSA-N

物化性质

• 沸点：
  450.6±37.0 °C(Predicted)
• 密度：
  1.158±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  腺嘌呤 、 hexestrol-3',4'-quinone 在 溶剂黄146 作用下， 以 水 为溶剂， 生成 、 4-(6-aminopurin-3-yl)-5-[4-(4-hydroxyphenyl)hexan-3-yl]benzene-1,2-diol
  参考文献：
  名称：

  Formation of the depurinating N3adenine and N7guanine adducts by reaction of DNA with hexestrol-3′,4′-quinone or enzyme-activated 3′-hydroxyhexestrol

  摘要：

  The nonsteroidal synthetic estrogen hexestrol (HES), which is diethylstilbestrol hydrogenated at the C-3-C-4 double bond, is carcinogenic. Its major metabolite is the catechol, 3'-OH-HES, which can be metabolically converted to the catechol quinone. HES-3',4'-Q. Study of HES was undertaken with the scope to substantiate evidence that natural catechol estrogen-3.4-quinones are endogenous carcinogenic metabolites. HES-3',4'-Q was previously shown to react with deoxyguanosine to form the depufinating adduct 3'-OH-HES-6'-N7Gua by 1.4-Michael addition [Jan S-T, Devanesan PD, Stack DE, Ramanathan R, Byun J, Gross ML et a]. Metabolic activation and formation of DNAadducts of hexestrol,a synthetic nonsteroidal carcinogenic estrogen. Chem Res Toxicol 1998:11:412-9.]. We report here formation of the depurinating adduct 3'-OH-HES-6'-N3Ade by reaction of HES-3',4'-Q with Ade by 1,4-Michael addition. The structure of the N3Ade adduct was established by NMR and MS. We also report here formation of the depurinating 3'-OH-HES-6'-N7Gua and 3'-OH-HES-6-N'3Ade adducts by reaction of HES-3',4'-Q with DNA or by activation of 3'-OH-HES by tyrosinase, lactoperoxidase. prostaglandin H synthase or 3-meilty1cholanthrene-induced rat liver microsomes in the presence of DNA. The N3Ade adduct was released instantaneously from DNA, whereas the N17Gua adduct was released with a half-life of approximately 3 h. Much lower (<1%) levels of unidenfified stable adducts were detected in the DNA from these reactions. These results are similar to those obtained by reaction of endogenous catechol estrogen-3.4-quinones with DNA. The similarities extend to the instantaneously-depurinating N3Ade adducts and relatively slowly-depurinating N7Gua adducts. The endogenous estrogens, estrone and estradiol, their 4-catechol estrogens and RES are carcinogenic in the kidney of Syrian golden hamsters. These results suggest that estrone (estradiol)-3,4-quinones and HES-3'.4'-Q are the ultimate carcinogenic metabolites of the natural and synthetic estrogens. respectively. Reaction of the electrophilic quinones by 1,4-Michael addition with DNA at the nucleophilic N-3 of Ade and N-7 of Gua is suggested to be the major critical step in tumor initiation by these compounds. (C) 2004 Elsevier Inc. All rights reserved

  DOI：

  10.1016/j.steroids.2004.09.012
• 作为产物：
  描述：

  3'-hydroxy-hexestrol 在 silver(l) oxide 作用下， 以 丙酮 为溶剂， 反应 0.5h， 以99%的产率得到hexestrol-3',4'-quinone
  参考文献：
  名称：

  氧化银氧化后由3'-羟基二乙基己烯雌酚形成新的螺-醌

  摘要：

  人致癌物己烯雌酚（DES）代谢为3'-羟基己烯雌酚（3'-OH-DES）（1）。在CH 2 Cl 2中用氧化银对邻苯二酚代谢物进行化学氧化，可以定量收率得到新型螺醌（3）。保护酚羟基并随后氧化，以优异的产率得到4″ -OCH 3 -DES-3′，4′-Q（5）。

  DOI：

  10.1016/j.tetlet.2005.04.131

文献信息

• Slow loss of deoxyribose from the N7deoxyguanosine adducts of estradiol-3,4-quinone and hexestrol-3′,4′-quinone.
  作者：Muhammad Saeed、Muhammad Zahid、Sandra J. Gunselman、Eleanor Rogan、Ercole Cavalieri

  DOI：10.1016/j.steroids.2004.09.011

  日期：2005.1

  A variety of evidence has been obtained that estrogens are weak tumor initiators. A major step in the multi-stage process leading to tumor initiation involves metabolic formation of 4-catechol estrogens from estradiol (E,) and/or estrone and further oxidation of the catechol estrogens to the corresponding catechol estrogen quinones. The electrophilic catechol quinones react with DNA mostly at the N-3 of adenine (Ade) and N-7 of guanine (Gua) by 1,4-Michael addition to form depurinating adducts. The N3Ade adducts depurinate instantaneously, whereas the N7Gua adducts depurinate with a half-life of several hours. Only the apurinic sites generated in the DNA by the rapidly depurinatingN3Ade adducts appear to produce mutations by error-prone repair. Analogously to the catechol estrogen-3.4-quinones, the synthetic nonsteroidal estrogen hexestrol- 3',4'-quinone (HES-3',4'-Q) reacts with DNA at the N-3 of Ade and N-7 of Gua to form deputinating adducts. We report here an additional similarity between the natural estrogen E-2 and the synthetic estrogen HES, namely, the slow loss of deoxyribose from the N7deoxyguanosine (N7dG) adducts formed by reaction of E-2-3.4-Q or HES-3'.4'-Q with dG. The half-life of the loss of deoxyribose from the N7dG adducts to form the corresponding 4-OHE2-I-N7Gua and 3'-OH-HES-6'-N7Gua is 6 or 8 h, respectively. The slow cleavage of this glycosyl bond in DNA seems to limit the ability of these adducts to induce mutations. (C) 2004 Elsevier Inc. All rights reserved.
• UNIFYING MECHANISM AND METHODS TO PREVENT CANCER AND NEURODEGENERATIVE DISEASES
  申请人：Cavalieri Ercole L.

  公开号：US20090312391A1

  公开（公告）日：2009-12-17

  The present invention relates to methods for preventing the development of cancer or neurodegenerative diseases by administering N-Acetylcysteine (NAC), melatonin, or a combination thereof. The present invention also relates to methods for diagnosing cancer and/or neurdegenerative disease by detecting or determining the amount of dopamine metabolites, 4-CE, 2-CE, methylation of CE or CE-Q conjugates.
• Formation of the depurinating N3adenine and N7guanine adducts by reaction of DNA with hexestrol-3′,4′-quinone or enzyme-activated 3′-hydroxyhexestrol
  作者：Muhammad Saeed、Sandra J. Gunselman、Sheila Higginbotham、Eleanor Rogan、Ercole Cavalieri

  DOI：10.1016/j.steroids.2004.09.012

  日期：2005.1

  The nonsteroidal synthetic estrogen hexestrol (HES), which is diethylstilbestrol hydrogenated at the C-3-C-4 double bond, is carcinogenic. Its major metabolite is the catechol, 3'-OH-HES, which can be metabolically converted to the catechol quinone. HES-3',4'-Q. Study of HES was undertaken with the scope to substantiate evidence that natural catechol estrogen-3.4-quinones are endogenous carcinogenic metabolites. HES-3',4'-Q was previously shown to react with deoxyguanosine to form the depufinating adduct 3'-OH-HES-6'-N7Gua by 1.4-Michael addition [Jan S-T, Devanesan PD, Stack DE, Ramanathan R, Byun J, Gross ML et a]. Metabolic activation and formation of DNAadducts of hexestrol,a synthetic nonsteroidal carcinogenic estrogen. Chem Res Toxicol 1998:11:412-9.]. We report here formation of the depurinating adduct 3'-OH-HES-6'-N3Ade by reaction of HES-3',4'-Q with Ade by 1,4-Michael addition. The structure of the N3Ade adduct was established by NMR and MS. We also report here formation of the depurinating 3'-OH-HES-6'-N7Gua and 3'-OH-HES-6-N'3Ade adducts by reaction of HES-3',4'-Q with DNA or by activation of 3'-OH-HES by tyrosinase, lactoperoxidase. prostaglandin H synthase or 3-meilty1cholanthrene-induced rat liver microsomes in the presence of DNA. The N3Ade adduct was released instantaneously from DNA, whereas the N17Gua adduct was released with a half-life of approximately 3 h. Much lower (<1%) levels of unidenfified stable adducts were detected in the DNA from these reactions. These results are similar to those obtained by reaction of endogenous catechol estrogen-3.4-quinones with DNA. The similarities extend to the instantaneously-depurinating N3Ade adducts and relatively slowly-depurinating N7Gua adducts. The endogenous estrogens, estrone and estradiol, their 4-catechol estrogens and RES are carcinogenic in the kidney of Syrian golden hamsters. These results suggest that estrone (estradiol)-3,4-quinones and HES-3'.4'-Q are the ultimate carcinogenic metabolites of the natural and synthetic estrogens. respectively. Reaction of the electrophilic quinones by 1,4-Michael addition with DNA at the nucleophilic N-3 of Ade and N-7 of Gua is suggested to be the major critical step in tumor initiation by these compounds. (C) 2004 Elsevier Inc. All rights reserved
• Novel spiro-quinone formation from 3′-hydroxydiethylstilbestrol after oxidation with silver oxide
  作者：Muhammad Saeed、Eleanor Rogan、Ercole Cavalieri

  DOI：10.1016/j.tetlet.2005.04.131

  日期：2005.6

  carcinogen diethylstilbestrol (DES) is metabolized into 3′-hydroxydiethylstilbestrol (3′-OH-DES) (1). Chemical oxidation of the catechol metabolites with silver oxide in CH2Cl2 affords a novel spiro-quinone (3) in quantitative yield. Protection of the phenolic OH group followed by oxidation gives 4″-OCH3-DES-3′,4′-Q (5) in excellent yield.

  人致癌物己烯雌酚（DES）代谢为3'-羟基己烯雌酚（3'-OH-DES）（1）。在CH 2 Cl 2中用氧化银对邻苯二酚代谢物进行化学氧化，可以定量收率得到新型螺醌（3）。保护酚羟基并随后氧化，以优异的产率得到4″ -OCH 3 -DES-3′，4′-Q（5）。