(-)-(2R,3R)-5,7-dihydroxy-2-(3',5'-dihydroxy-4'-methoxyphenyl)chroman-3-yl 3''-hydroxy-4'',5''-dimethoxybenzoate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: (-)-(2R,3R)-5,7-dihydroxy-2-(3',5'-dihydroxy-4'-methoxyphenyl)chroman-3-yl 3''-hydroxy-4'',5''-dimethoxybenzoate
• 英文别名: [(2R,3R)-2-(3,5-dihydroxy-4-methoxyphenyl)-5,7-dihydroxy-3,4-dihydro-2H-chromen-3-yl] 3-hydroxy-4,5-dimethoxybenzoate
• 化学式: C₂₅H₂₄O₁₁
• 分子量: 500.459
• InChiKey: FWAFYKCLVHZLSM-FGZHOGPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  164
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  3-benzyloxy-4,5-dimethoxybenzoyl chloride 在 palladium dihydroxide 4-二甲氨基吡啶 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 (-)-(2R,3R)-5,7-dihydroxy-2-(3',5'-dihydroxy-4'-methoxyphenyl)chroman-3-yl 3''-hydroxy-4'',5''-dimethoxybenzoate
  参考文献：
  名称：

  Regiospecific and enantioselective synthesis of methylated metabolites of tea catechins

  摘要：

  The regiospecific and enantioselective syntheses of various methylated regioisomers of epicatechin gallate (EGC) and epigallocatechin gallate (EGCG) have been achieved. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.04.010

文献信息

• Solid-Phase Synthesis of a Combinatorial Methylated (±)-Epigallocatechin Gallate Library and the Growth-Inhibitory Effects of these Compounds on Melanoma B16 Cells
  作者：Hiroshi Tanaka、Maasa Yamanouchi、Haruko Miyoshi、Keisuke Hirotsu、Hirofumi Tachibana、Takashi Takahashi

  DOI：10.1002/asia.201000372

  日期：——

  We report on the solid‐phase synthesis of a combinatorial methylated (±)‐epigallocatechin gallate (EGCG) library and its biological evaluation. Epigallocatechin gallate (EGCG) and its methylated derivatives, which are members of the catechin family, exhibit various anti‐cancer effects. The solid‐phase synthesis of methylated EGCG involves the preparation of the α‐acyloxyketone by the coupling of a

  我们报告了组合甲基化（±）-表没食子儿茶素没食子酸酯（EGCG）库的固相合成及其生物学评估。儿茶素家族的成员表没食子儿茶素没食子酸酯（EGCG）及其甲基化衍生物具有多种抗癌作用。甲基化EGCG的固相合成涉及通过固相负载的醛与酮和酸的偶联来制备α-酰氧基酮。固体负载的α-酰氧基酮的后续释放和还原醚化反应以良好的总收率提供了受保护的EGCG。成功制备了64种甲基化EGCG。还检查了甲基化EGCG文库的生长抑制作用。尽管EGCG的甲基化通常会导致生长抑制作用降低，7-OMe EGCG的生长抑制作用与EGCG相当。7-OMe EGCG由于具有更高的生物利用度，因此是有吸引力的候选药物。
• Identification and Characterization of Methylated and Ring-Fission Metabolites of Tea Catechins Formed in Humans, Mice, and Rats
  作者：Xiaofeng Meng、Shengmin Sang、Nanqun Zhu、Hong Lu、Shuqun Sheng、Mao-Jung Lee、Chi-Tang Ho、Chung S. Yang

  DOI：10.1021/tx010184a

  日期：2002.8.1

  (-)-Epigallocatechin gallate (EGCG), the most abundant tea catechin, has been proposed to be beneficial to human health based on its strong antioxidative and other biological activities in vitro. Inadequate knowledge regarding the bioavailability and biotransformation of EGCG in humans, however, has limited our understanding of its possible beneficial health effects. In this study, 4',4"-di-O-methyl-EGCG (4',4"-DiMeEGCG) was detected in human plasma and urine by LC/MS/MS following green tea ingestion. Both 4',4"-DiMeEGCG and EGCG reached peak plasma values (20.5 +/- 7.7 and 145.4 +/- 31.6 nM, respectively, in 4 subjects) at 2 h after the dose. The half-lives of 4',4"-DiMeEGCG and EGCG were 4.1 +/- 0.8 and 2.7 +/- 0.9 h, respectively. The cumulative urinary excretion of 4',4"-DiMeEGCG during a 24 h period was 140.3 +/- 48.6,mug, about 5-fold higher than that of EGCG, but the excreted 4',4"-DiMeEGCG and EGCG in urine only accounted for about 0.1% of ingested EG-CG. (-)-5-(3',4',5'-Trihydroxyphenyl)-gamma-valerolactone (M4) and (-)-5-(3',4'-dihydroxyphenyl)-gamma-valerolactone (M6), along with another possible ring-fission metabolite, (-)-5-(3',5'-dihydroxyphenyl)-gamma-valerolactone (M6'), were detected in human urine after green tea ingestion. The cumulative excretion of M4, M6', and M6 during a 24 h period ranged from 75,mug to 1.2 mg, 0.6 to 6 mg, and 0.6 to 10 mg, respectively. The combined excretion of all three ring-fission metabolites accounted for 1.5-16% of ingested catechins. M4, M6', and M6 were all observed after the ingestion of pure EGCG or EGC by human subjects, whereas only M6 was produced after EC ingestion. These metabolites as well as monomethylated EGCG were detected in mice and rats after tea or EGCG administration, and the tissue levels reflected the rather low bioavailability of EGCG in rats. The presently characterized methylated EGCG metabolites and ring-fission products exist in substantial quantities and may contribute to the biological activities of tea.

  （-）-表没食子儿茶素-3- gallate（EGCG），茶叶中最丰富的儿茶素，因其在体外具有强大的抗氧化和其他生物活性，已提出对人类健康有益。然而，对人体内EGCG的生物利用度和生物转化了解不足，限制了我们对其可能有益健康效果的理解。在本研究中，绿茶摄入后，通过液相色谱-串联质谱法（LC/MS/MS）在人体血浆和尿液中检测到4',4"-二-O-甲基-EGCG（4',4"-DiMeEGCG）。4',4"-DiMeEGCG和EGCG在给药后2小时达到血浆峰值浓度（分别为20.5 ± 7.7 nM和145.4 ± 31.6 nM，在4名受试者中测得）。4',4"-DiMeEGCG和EGCG的半衰期分别为4.1 ± 0.8小时和2.7 ± 0.9小时。在24小时内，4',4"-DiMeEGCG的累积尿排泄量为140.3 ± 48.6微克，约为EGCG排泄量的5倍，但在尿液中排泄的4',4"-DiMeEGCG和EGCG仅占摄入EG.cg的约0.1%。在绿茶摄入后的人尿中检测到（-）-5-（3',4',5'-三羟基苯基）-γ-戊内酯（M4）、（-）-5-（3',4'-二羟基苯基）-γ-戊内酯（M6），以及另一种可能的环裂解代谢物，（-）-5-（3',5'-二羟基苯基）-γ-戊内酯（M6'）。在24小时内，M4、M6'和M6的累积排泄量分别为75微克至1.2毫克、0.6至6毫克和0.6至10毫克。所有三种环裂解代谢物的联合排泄量占摄入儿茶素的1.5%-16%。M4、M6'和M6在人类受试者摄入纯EGCG或EGC后被观察到，而在摄入EC后仅产生M6。这些代谢物以及单甲基化EGCG在茶或EGCG给药后被检测到存在于小鼠和大鼠中，组织水平反映了大鼠中EGCG的较低生物利用度。目前表征的甲基化EGCG代谢物和环裂解产物存在大量，并可能有助于茶的生物活性。
• Regiospecific and enantioselective synthesis of methylated metabolites of tea catechins
  作者：Sheng Biao Wan、Q. Ping Dou、Tak Hang Chan

  DOI：10.1016/j.tet.2006.04.010

  日期：2006.6

  The regiospecific and enantioselective syntheses of various methylated regioisomers of epicatechin gallate (EGC) and epigallocatechin gallate (EGCG) have been achieved. (c) 2006 Elsevier Ltd. All rights reserved.