7,8-二氢-7alpha,8beta-二羟基苯并[a]芘 | 62314-67-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 芘
• 中文名称: 7,8-二氢-7alpha,8beta-二羟基苯并[a]芘
• 英文名称: (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene
• 英文别名: (+/-)-benzopyrene-trans-7,8-dihydrodiol；(+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzopyrene；(E)-7,8-Dihydrobenzo(a)pyrene-7,8-diol；(7S,8S)-7,8-dihydrobenzo[a]pyrene-7,8-diol
• CAS: 62314-67-4；57404-88-3
• 化学式: C₂₀H₁₄O₂
• 分子量: 286.33
• InChiKey: YDXRLMMGARHIIC-PXNSSMCTSA-N

物化性质

• 沸点：
  388.69°C (rough estimate)
• 密度：
  1.1197 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

SDS

反应信息

• 作为反应物：
  描述：

  7,8-二氢-7alpha,8beta-二羟基苯并[a]芘 在 4-硝基过氧化苯甲酸 作用下， 生成 (7R,8S,9R,10S)-rel-7,8,9,10-四氢苯并[a]芘-7,8,9,10-四醇
  参考文献：
  名称：

  致癌物苯并[a] py的高致突变性7,8-二醇9,10-环氧化物的合成与反应。

  摘要：

  DOI：

  10.1021/ja00447a053
• 作为产物：
  描述：

  苯并[a]芘 在 potassium phosphate buffer 、 recombinant human cytochrome P₄₅₀ 、 还原型辅酶II(NADPH)四钠盐 作用下， 生成 7,8-二氢-7alpha,8beta-二羟基苯并[a]芘
  参考文献：
  名称：

  Metabolism of Benzo[a]pyrene to trans-7,8-Dihydroxy-7,8-dihydrobenzo[a]pyrene by Recombinant Human Cytochrome P450 1B1 and Purified Liver Epoxide Hydrolase

  摘要：

  Recombinant human enzymes expressed in membranes obtained from Escherichia coli transformed with cytochrome P450 (P450) and NADPH-P450 reductase cDNAs were used to identify the human P450 enzymes that are most active in catalyzing the oxidative transformation of benzo[a]pyrene in vitro. Activation of benzo[a]pyrene to genotoxic products that cause induction of umu gene expression in Salmonella typhimurium NM2009 by P450 1A1 and P450 1B1 enzymes was found to be enhanced by inclusion of purified epoxide hydrolase (isolated from rat or human livers) with the reaction mixture. High-performance liquid chromatographic analysis showed that P450 1B1 catalyzed benzo[a]pyrene to trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene at level of similar to 3 nmol min(-1) nmol of P450(-1) only when epoxide hydrolase was present and P450 1A1 (with the hydrolase) was able to catalyze benzo[la]pyrene at one-tenth of the activity catalyzed by P450 1B1. Kinetic analysis showed that ratio of V-max to K-m for the formation of trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene in this assay system was 3.2-fold higher in CYP1B1 than in CYP1A1. Other human P450s (including P450s 1A2, 2E1, and 3A4) were found to have very low or undetectable activities toward the formation of trans-7,8-dihydroxy- 7,8-dihydrobenzo[a] pyrene. A reconstituted system containing purified P450 1B1, rabbit liver NADPH-P450 reductase, and human liver epoxide hydrolase was found to catalyze benzo[a]pyrene to trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene at a rate of 0.86 nmol min(-1) nmol of P450-1; the activities were found to be largely dependent on the presence of sodium cholate in the system. These results suggest that P450 1B1 is a principal enzyme in catalyzing the oxidation of benzo[a]pyrene to trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene and that the catalytic functions of P450 1B1 may determine the susceptibilities of individuals to benzo[a]pyrene carcinogenesis.

  DOI：

  10.1021/tx990028s

文献信息

• Synthesis of 13C4-labelled oxidized metabolites of the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene
  作者：Anhui Wu、Daiwang Xu、Ding Lu、Trevor M. Penning、Ian A. Blair、Ronald G. Harvey

  DOI：10.1016/j.tet.2012.05.130

  日期：2012.9

  sensitive stable isotope dilution LC/MS method for analysis of BaP metabolites. We now report efficient syntheses of 13C4-BaP and the complete set of its 13C4-labelled oxidized metabolites needed as internal standards They include the metabolites not involved in carcinogenesis (Group A) and the metabolites implicated in initiation of cancer (Group B). The synthetic approach is novel, entailing use of Pd-catalyzed

  多环芳烃 (PAH)，例如苯并 [ a ] 芘 (B a P)，是普遍存在的环境污染物，与导致肺癌有关。B a P 是烟草烟雾的一种成分，通过酶促转化为与 DNA 相互作用的活性形式。我们之前报道了一种用于分析 B a P 代谢物的灵敏的稳定同位素稀释 LC/MS 方法的开发。我们现在报告了13 C 4 -B a P 的有效合成及其完整的13 C 4标记氧化代谢物，需要作为内标。它们包括不参与致癌作用的代谢物（A 组））和与癌症发生有关的代谢物（B组）。该合成方法是新颖的，需要使用 Pd 催化的 Suzuki、Sonogashira 和 Hartwig 交叉偶联反应与 PtCl 2催化的炔属化合物环化反应相结合。这种合成方法需要更少的步骤，使用更温和的条件，并且产物分离比传统的 PAH 合成方法更简单。13 C 4 -B a P 和13 C 4 -B a P-8-ol的合成各只需要四步，并且13
• Synthesis of the <i>o</i>-Quinones and Other Oxidized Metabolites of Polycyclic Aromatic Hydrocarbons Implicated in Carcinogenesis
  作者：Ronald G. Harvey、Qing Dai、Chongzhao Ran、Trevor M. Penning

  DOI：10.1021/jo030348n

  日期：2004.3.1

  benzo[a]pyrene (BPQ), 7,12-dimethylbenz[a]anthracene (DMBAQ), and benz[a]anthracene (BAQ), implicated as active carcinogenic metabolites of the parent polycyclic aromatic hydrocarbons (PAHs), are reported. These PAH quinones also serve as starting compounds for the synthesis of the other active metabolites of these PAHs thought to be involved in their mechanism(s) of carcinogenesis. The latter include the corresponding

  苯并[ a ] py（BPQ），7,12-二甲基苯并[ a ]蒽（DMBAQ）和苯并[ a ]蒽（BAQ）的邻苯醌衍生物的高效合成，被认为是母体的活性致癌代谢物报道了多环芳烃（PAH）。这些PAH醌也用作这些PAH的其他活性代谢产物合成的起始化合物，这些活性代谢产物被认为与它们的致癌机理有关。后者包括相应Ó -catechols，反式-dihydrodiols，以及相应的抗-和顺-二醇环氧化物。
• Highly Diastereoselective Synthesis of Nucleoside Adducts from the Carcinogenic Benzo[<i>a</i>]pyrene Diol Epoxide and a Computational Analysis
  作者：Mahesh K. Lakshman、John C. Keeler、Felix N. Ngassa、John H. Hilmer、Padmanava Pradhan、Barbara Zajc、Kathryn A. Thomasson

  DOI：10.1021/ja063902u

  日期：2007.1.1

  diastereoselective dihydroxylation wherein phenylboronic acid was a water surrogate. The resulting boronate ester was converted to a tetraol derivative in which two of the four hydroxyl groups (trans 7, 8) were protected as benzoate esters while the remaining two (cis 9, 10) were free. The cis glycol entity was then subjected to a reaction with 1-chlorocarbonyl-1-methylethylacetate to yield an intermediate chloro

  对应于致癌物 (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a 的顺式开环的核苷加合物的非对映选择性合成] 芘 (BaP DE-2) 由 2'-脱氧腺苷和 2'-脱氧鸟苷组成。关键中间体 (+/-)-10alpha-amino-7beta,8alpha,9alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene 是通过高度非对映选择性二羟基化合成的，其中苯基硼酸是水的替代物。所得硼酸酯转化为四醇衍生物，其中四个羟基中的两个（反式 7、8）被保护为苯甲酸酯，而剩余的两个（顺式 9、10）是游离的。然后使顺式二醇实体与乙酸1-氯羰基-1-甲基乙基酯反应，得到中间体氯单乙酰氧基二苯甲酸酯。用叠氮化物置换卤化物、酯的完全裂解和叠氮化物的催化还
• Improved formal preparation of enantiomerically pure anti-benzo[a]pyrene diol epoxide
  作者：George R. Negrete、Thomas Meehan

  DOI：10.1016/s0040-4039(00)76952-8

  日期：1994.7

  We report an improved, economical formal route to enantiomerically pure anti-benzo[a]pyrene diol epoxide (BPDE). A trimethylaluminum catalyzed regio- and stereoselective opening of racemic 7,8-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene with Mosher's acid delivers benzylic esters exclusively. This step is a significant improvement over the lack of regioselectivity of standard procedures. We also show that

  我们报告了对映体纯的抗-苯并[ a ]二醇环氧（BPDE）的一种改进的，经济的正式途径。三甲基铝与Mosher's酸催化外消旋7,8-环氧-7,8,9,10-四氢苯并[ a ] gio的区域和立体选择性开环，仅提供苄基酯。该步骤是对标准方法缺乏区域选择性的重大改进。我们还表明，后续化学步骤的修饰进一步缩短了对映体纯的抗-BPDE的制备。
• Enantioselective synthesis of the tumorigenic anti-diol epoxide metabolites of benzo[a]pyrene
  作者：Ronald G. Harvey、Xiao-Qing Tang

  DOI：10.1016/0040-4039(95)00385-p

  日期：1995.4

  Efficient, highly enantioselective syntheses of (+) and (−)-anti-benzo[a]pyrene diol epoxide (BPDE) from 9,10-dihydrobenzo[a]pyrene are described. Initial epoxidation catalyzed by (salen) Mn(III) complex gives 7,8-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (>90% ee). Acid-catalyzed hydration occurs regio- and stereo-selectively to furnish the trans-tetrahydrodiols which are converted into the optically

  描述了由9,10-二氢苯并[a] py制成的高效，高对映选择性的（+）和（-）-抗-苯并[a] py二醇环氧化物（BPDE）。（salen）Mn（III）配合物催化的初始环氧化反应得到7,8-环氧-7,8,9,10-四氢苯并[a] py（> 90％ee）。酸催化的水合在区域和立体选择性地发生，以提供反式-四氢二醇，该反式-四氢二醇被转化为光学活性的抗-BPDE。