13-(R,S)-dihydrodaunorubicin | 28008-55-1

• 物质功能分类: 原料药 - 抗肿瘤药 - 抗生素类抗肿瘤药
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: 13-(R,S)-dihydrodaunorubicin
• 英文别名: 13-dihydrodaunorubicin；daunorubicinol；DNRol；(7S,9S)-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(1-hydroxyethyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione
• CAS: 28008-55-1
• 化学式: C₂₇H₃₁NO₁₀
• 分子量: 529.544
• InChiKey: HJEZFVLKJYFNQW-FKKRWUELSA-N

物化性质

• 熔点：
  >173°C (dec.)
• 沸点：
  609.35°C (rough estimate)
• 密度：
  1.3345 (rough estimate)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  38
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  189
• 氢给体数：
  6
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  13-(R,S)-dihydrodaunorubicin 在 盐酸 作用下， 反应 1.0h， 生成 (8S,10S)-7,8,9,10-四氢-6,8,10,11-四羟基-8-(1S)-1-羟基乙基-1-甲氧基-5,12-并四苯醌
  参考文献：
  名称：

  Penco, Sergio; Cassinelli, Giuseppe; Vigevani, Aristide, Gazzetta Chimica Italiana, 1985, vol. 115, # 3, p. 195 - 198

  摘要：

  DOI：
• 作为产物：
  描述：

  道诺霉素 在 human liver dihydrodiol dehydrogenase 2 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 phosphate buffer 为溶剂， 生成 13-(R,S)-dihydrodaunorubicin
  参考文献：
  名称：

  人肝中的二氢二醇脱氢酶，羰基还原酶和醛还原酶可还原药物酮。

  摘要：

  在这项研究中，我们比较了人肝细胞溶质的均相羰基还原酶，醛还原酶和三种二氢二醇脱氢酶对10种带有酮基的药物的酶促还原作用。三种二氢二醇脱氢酶中至少一种，在某些情况下，全部还原了十种药物。在这些纳洛酮中，纳曲酮，倍氟洛尔，乙炔酸和酮洛芬是脱氢酶特异的底物。羰基还原酶和/或醛还原酶大大降低了其他药物-氟哌啶醇，甲吡酮，洛索洛芬，柔红霉素和乙酰己酰胺的含量。二氢二醇脱氢酶还显示氟哌啶醇和洛索洛芬的Km值低于羰基还原酶的Km值。结果表明，三种二氢二醇脱氢酶以及两种还原酶，

  DOI：

  10.1016/0006-2952(95)00124-i

文献信息

• Reduction of drug ketones by dihydrodiol dehydrogenases, carbonyl reductase and aldehyde reductase of human liver
  作者：Hirotami Ohara、Yoshiyuki Miyabe、Yoshihiro Deyashiki、Kazuya Matsuura、Akira Kara

  DOI：10.1016/0006-2952(95)00124-i

  日期：1995.7

  In this study, we compared the enzymatic reduction of 10 drugs with a ketone group by homogeneous carbonyl reductase, aldehyde reductase and three dihydrodiol dehydrogenases of human liver cytosol. At least one and in some cases all of the three dihydrodiol dehydrogenases reduced each of the ten drugs. Among these naloxone, naltrexone, befunolol, ethacrynic acid and ketoprofen were substrates specific

  在这项研究中，我们比较了人肝细胞溶质的均相羰基还原酶，醛还原酶和三种二氢二醇脱氢酶对10种带有酮基的药物的酶促还原作用。三种二氢二醇脱氢酶中至少一种，在某些情况下，全部还原了十种药物。在这些纳洛酮中，纳曲酮，倍氟洛尔，乙炔酸和酮洛芬是脱氢酶特异的底物。羰基还原酶和/或醛还原酶大大降低了其他药物-氟哌啶醇，甲吡酮，洛索洛芬，柔红霉素和乙酰己酰胺的含量。二氢二醇脱氢酶还显示氟哌啶醇和洛索洛芬的Km值低于羰基还原酶的Km值。结果表明，三种二氢二醇脱氢酶以及两种还原酶，
• 5-Deoxy, 12-Deoxy, 5,12-Bisdeoxy, and 4,5,12-Trisdeoxy Anthracyclines: Synthesis of New Analogues of Daunorubicin and Doxorubicin by Controlled Deoxygenation of the C-Ring.
  作者：Donald W. Cameron、Geoffrey I. Feutrill、Peter G. Griffiths

  DOI：10.1071/ch99151

  日期：——

  Hydrogenation of the anthracyclines daunorubicin (1) and doxorubicin (2) gave selective deoxygenation at position 5. Hydride reduction of (1) and (2) gave complementary regiocontrol, leading to 12-deoxygenation or 5,12- bisdeoxygenation. This chemistry allows retention of the 7-glycoside and the side-chain carbonyl groups. It has led to new anthracycline families possessing all of the stereochemical and most of the spatial characteristics of the parent compounds (1) and (2). These are typified by 5-deoxy (12), (15); 12-deoxy (22), (23); 5,12-bisdeoxy (34), (35); and 4,5,12-trisdeoxy systems (36). All possess high anticancer activity.

  蒽喜啉类化合物多柔比星（1）和阿霉素（2）的氢化反应在位置5上发生选择性脱氧作用。对（1）和（2）的氢化还原反应产生了互补的位置控制，导致12-脱氧或5,12-双脱氧。这种化学反应可保留7-糖苷和侧链酮基团。它已经导致新的蒽喜啉类家族，具有母体化合物（1）和（2）的所有立体化学特性和大部分空间特性。这些家族的代表包括5-去氧（12），（15）；12-去氧（22），（23）；5,12-双去氧（34），（35）；以及4,5,12-三去氧系统（36）。所有这些都具有高抗癌活性。
• SYNTHESIS OF EPIRUBICIN FROM 13-DIHYDRODAUNORUBICINE
  申请人：Zabudkin F. Alexander

  公开号：US20070142309A1

  公开（公告）日：2007-06-21

  A method of preparing an anthracyclin such as epirubicin from a starting material comprising 13-dihydrodaunorubicine (13-daunorubicinol). The method comprises producing N-Trifluoroacetyl-13-daunorubicinol from 13-daunorubicinol by acylation. The N-Trifluoroacetyl-13-daunorubicinol is reacted with an aprotic solvent and an acylating agent to produce an intermediate sulfoxy salt which is treated with a strong base to produce 4′-keto-N-Trifluoroacetyldaunorubicin. The 4′-keto-N-Trifluoroacetyldaunorubicin is reacted with a reducing agent, such as borohydride of an alkaline metal, to produce N-Trifluoroacetyl-4′-epi-daunorubicin. The N-Trifluoroacetyl-4′-epi-daunorubicin is hydrolyzed in a basic solution to produce an intermediate compound. The intermediate compound is reacted with a halogenizing agent to produce a 14-Hal-derivative. The 14-Hal derivative is hydrolized in the presence of a formate of an alkaline metal to produce the desired final compound.

  一种从含有13-去氢异柔红霉素（13-去异柔红霉素醇）的起始物质制备类蒽环素（如表柔比星）的方法。该方法包括通过酰化制备N-三氟乙酰基-13-去异柔红霉素醇（13-DA醇）。将N-三氟乙酰基-13-DA醇与无水溶剂和酰化剂反应，产生中间的磺酸盐，该磺酸盐经强碱处理后产生4'-酮基-N-三氟乙酰基异柔红霉素。将4'-酮基-N-三氟乙酰基异柔红霉素与还原剂（如一种碱金属的硼氢化物）反应，产生N-三氟乙酰基-4'-epi-异柔红霉素。将N-三氟乙酰基-4'-epi-异柔红霉素在碱性溶液中水解，产生中间化合物。将中间化合物与卤化剂反应，产生14-Hal衍生物。在碱性金属甲酸盐的存在下水解14-Hal衍生物，产生所需的最终化合物。
• Method of producing epirubicin and novel production intermediate thereof
  申请人：MEIJI SEIKA PHARMA CO., LTD.

  公开号：US10301343B2

  公开（公告）日：2019-05-28

  According to the present invention, it is possible to efficiently remove 13-dihydroepi-daunorubicin and 4′-epi-feudomycin, which are typical impurities possibly contained in 4′-epi-daunorubicin as a starting material, by using an organic acid salt of 4′-epi-daunorubicin or a hydrate or solvate thereof as a novel production intermediate, thus making it possible to produce high-purity epirubicin.

  根据本发明，通过使用 4′-epi-daunorubicin 的有机酸盐或其水合物或溶物作为新型生产中间体，可以有效去除 4′-epi-daunorubicin 作为起始原料可能含有的典型杂质 13-二氢表-daunorubicin 和 4′-epi-feudomycin，从而生产出高纯度表柔比星。
• Synthesis and antitumor activity of new d-galactose-containing derivatives of doxorubicin
  作者：Eugenia N. Olsufyeva、Anna N. Tevyashova、Ivan D. Trestchalin、Maria N. Preobrazhenskaya、David Platt、Anatole Klyosov

  DOI：10.1016/s0008-6215(03)00181-2

  日期：2003.6

  A general scheme of synthesis of antibiotic doxorubicin derivatives is based on the 13-dimethyl ketal of 14-bromodaunorubicin (4). The interaction of 4 with melibiose (5), lactose (6), 3-methoxy-4-O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-4-oxybenzaldehyde (12) or 4-O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-4-oxybenzaldehyde (13) by reductive alkylation followed by hydrolysis of the corresponding intermediate bromoketals produced 3'-N-[alpha-D-galactopyranosyl-(1-->6)-O-1-deoxy-D-glucit-1-yl]doxorubicin (7), 3'-N-[beta-D-galactopyranosyl-(1-->4)-O-1-deoxy-D-glucit-1-yl]doxorubicin (8), 3'-N-[3"-methoxy-4"-O-(beta-D-galactopyranosyl)-4"-oxybenzyl]doxorubicin (16), and 3'-N-[4"-O-(beta-D-galactopyranosyl)-4"-oxybenzyl]doxorubicin (17). Cytotoxic and antitumor activity of the synthesized drug candidates compared to the parent doxorubicin was studied using various experimental models, in particular, on mice bearing lymphocyte leukemia P-388 at single and multiple i.v. injection regimens. (C) 2003 Elsevier Science Ltd. All rights reserved.