14-溴柔红霉酮 | 29742-69-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 并四苯
• 中文名称: 14-溴柔红霉酮
• 英文名称: 14-bromodaunomycinone
• 英文别名: (7S,9S)-9-(2-bromoacetyl)-6,7,9,11-tetrahydroxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione
• CAS: 29742-69-6
• 化学式: C₂₁H₁₇BrO₈
• 分子量: 477.265
• InChiKey: JBZMHBHXHFZSMN-CWKPULSASA-N

物化性质

• 熔点：
  198-200 °C
• 沸点：
  723.0±60.0 °C(Predicted)
• 密度：
  1.810±0.06 g/cm3(Predicted)
• 溶解度：
  溶于氯仿

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  141
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  14-溴柔红霉酮 在 silver tetrafluoroborate 作用下， 以 二甲基亚砜 为溶剂， 以95%的产率得到阿霉酮
  参考文献：
  名称：

  Synthesis of 14-fluorodoxorubicin

  摘要：

  Abstraet-Synthesis of the novel anthracycline 14-fluorodoxorubicin is described. A key step in the synthesis is the hydrolysis of 14-bromo,14-fluoro derivative 14 with AgBF4 and DMSO, to give the geminal fluorohydrin system. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(02)00299-x
• 作为产物：
  描述：

  道诺霉素 生成 14-溴柔红霉酮
  参考文献：
  名称：

  Synthesis and antitumor activity of 7-O-(3,4-di-O-acetyl-2,6-dideoxy-α-l-lyxo-hexopyranosyl)adriamycinone

  摘要：

  The title compound (7), the 3'-acetoxy-4'-O-acetyl analog of adriamycin (doxorubicin), was synthesized in approximately 50% net yield from daunomycinone by bromination at C-14, glycosylation of the product at O-7 with 3,4-di-O-acetyl-2,6-dideoxy-alpha-L-lyxo-hexopyranosyl chloride, and replacement of the 14-bromo substituent by a hydroxyl group; other possible routes to 7 gave lower yields. The product 7, a non-aminated analog of the anthracycline antibiotics, showed high antitumor activity coupled with low acute toxicity in a broad range of tests in mice.

  DOI：

  10.1016/s0008-6215(00)85592-5

文献信息

• Adriamycin analogs. Preparation and biological evaluation of some novel 14-thiaadriamycins
  作者：Ramakrishnan Seshadri、Mervyn Israel、William J. Pegg

  DOI：10.1021/jm00355a003

  日期：1983.1

  N-(trifluoroacetyl)-14-bromodaunorubicin was used for reaction with thiols to yield thia analogues of the clinically active but non-DNA-binding adriamycin analogue N-(trifluoroacetyl)adriamycin 14-valerate (AD 32). Reaction of 14-bromoadunorubicin with alpha, omega-alkanedithiols gave bis(thiaadriamycin) analogues as potential difunctional intercalating agents. The aforementioned products, plus two related

  在碳酸钾存在下，甲醇中的14-溴金红霉素与硫醇缩合，导致抗肿瘤抗生素阿霉素的14-硫杂类似物形成。然而，N-（三氟乙酰基）-14-碘柔红霉素与硫醇的类似缩合反应总是导致氧化还原反应，形成N-（三氟乙酰基）柔红霉素和二硫化物。因此，将N-（三氟乙酰基）-14-溴金红霉素用于与硫醇反应，以产生具有临床活性但不结合DNA的阿霉素类似物N-（三氟乙酰基）阿霉素14-戊酸酯（AD 32）的硫代类似物。14-溴阿霉素与α，ω-链烷二硫醇的反应产生了双（硫代阿霉素）类似物作为潜在的双功能嵌入剂。上述产品，以及两个相关的苯基硒醚衍生物，检查了体外生长抑制，体内抗肿瘤活性，以及​​在适当情况下的DNA结合。许多试剂，特别是14-（乙氧甲氧基甲基）-14-硫代阿霉素和N-（三氟乙酰基）-14-苯基-14-硒代阿霉素，在体内对鼠L1210白血病具有活性。几种氨基糖苷未取代的14-硫代阿霉素类似物表现出与阿霉素相同的DNA结合特性。
• Convenient Syntheses of Daunomycinone‐7‐D‐Glucuronides and Doxorubicinone‐7‐D‐Glucuronides
  作者：Young S. Rho、Sun Y. Kim、Wan‐Joong Kim、Yeo Keun Yun、Hong Sig Sin、Dong Jin Yoo

  DOI：10.1081/scc-200030978

  日期：2004.1.1

  Abstract The first synthesis of new doxorubicin and daunomycin analogs containing glucuronic acid moieties instead of daunosamine are described. The desired products, daunomycinone‐7‐D‐glucuronide (DM7G, 10) and doxorubicinone‐7‐D‐glucuronide (DX7G, 11) were conveniently prepared through the glycosylation at 7‐hydroxyl group of daunomycinone (4) or 14‐acetoxydoxorubicinone (6) with glucuronic acid derivative

  摘要描述了含有葡糖醛酸部分而不是柔红胺的新型多柔比星和柔红霉素类似物的首次合成。目的产物柔红霉素-7-D-葡萄糖醛酸（DM7G，10）和多柔比星酮-7-D-葡萄糖醛酸（DX7G，11）通过柔红霉素（4）或14-乙酰氧基多柔比星酮的7-羟基糖基化方便地制备（ 6) 通过 Koenigs-Knorr 程序使用葡萄糖醛酸衍生物 7，然后使用 LiOH 水溶液和琥珀酸阳离子交换材料进行碱性脱乙酰。所有产品的异头构型和构象都通过基于报道的文献的 1H NMR 化学位移和 H-H 耦合常数的分配得到充分表征。
• Synthesis of adriamycin and 7,9-epiadriamycin
  申请人：Stanford Research Institute

  公开号：US04012448A1

  公开（公告）日：1977-03-15

  A process for the synthesis of adriamycin and 7,9-epiadriamycin, both active antineoplastic agents, in which 7-deoxydaunomycinone, in either the 9s or racemic (.+-.) form, is employed as the starting material, the process in one embodiment also being productive of the useful intermediate compound 4-methoxy-6,11-dihydroxy-7,8-dihydro-5,9(10H),12-naphthacenetrione. The process involves converting 7-deoxydaunomicinone successively to daunomycinone, adriamycinone, 14-0-p-anisyldiphenylmethyladriamycinone and finally to adriamycin or to both adriamycin and 7,9-epiadriamycin. When producing the latter mixture of diastereomers, the 7-deoxydaunomycinone starting material is first converted to racemate form by a process involving the successive production of 7-deoxydaunorubicinol, 4-methoxy-6,11-dihydroxy-7,8-dihydro-5,9(10H), 12-naphthacenetrione, (.+-.)-4-methoxy-9-cyano-6,9,11-trihydroxy-7,8,9,10-tetrahydro-5,12-naphth acenedione, (.+-.)-4-methoxy-9-cyano-9-(2'-tetrahydropyranyloxy)-6,11-dihydroxy-7,8,9, 10-tetrahydro-5,12-naphthacenedione and (.+-.)-7-deoxydaunomycinone.

  一种合成抗肿瘤活性物质阿霉素和7,9-环氧阿霉素的方法，其中7-去氧异柔红霉素酮（以9s或外消旋形式）作为起始物质，该方法在一种实施例中还产生有用的中间化合物4-甲氧基-6,11-二羟基-7,8-二氢-5,9（10H），12-萘酮。该过程涉及将7-去氧异柔红霉素酮依次转化为柔红霉素酮、阿霉素酮、14-0-p-茴香基二苯甲基阿霉素酮，最终转化为阿霉素或同时转化为阿霉素和7,9-环氧阿霉素。在生产后者的对映体混合物时，首先通过连续生产7-去氧柔红霉素醇、4-甲氧基-6,11-二羟基-7,8-二氢-5,9（10H），12-萘酮、（±）-4-甲氧基-9-氰基-6,9,11-三羟基-7,8,9,10-四氢-5,12-萘酚酮、（±）-4-甲氧基-9-氰基-9-（2'-四氢吡喃氧基）-6,11-二羟基-7,8,9,10-四氢-5,12-萘酚酮和（±）-7-去氧柔红霉素酮将起始物质转化为外消旋形式。
• Preparative procedures for conversion of daunorubicin into doxorubicin (Adriamycin) and 14-O-acetyldoxorubicin by way of 14-bromodaunorubicin
  作者：Derek Horton、Waldemar Priebe、auMarcos Sznaidman

  DOI：10.1016/0008-6215(88)80021-1

  日期：1988.12
• Synthesis of 14-fluorodoxorubicin
  作者：M. Berettoni、A. Cipollone、L. Olivieri、D. Palomba、F. Arcamone、C.A. Maggi、F. Animati

  DOI：10.1016/s0040-4039(02)00299-x

  日期：2002.4

  Abstraet-Synthesis of the novel anthracycline 14-fluorodoxorubicin is described. A key step in the synthesis is the hydrolysis of 14-bromo,14-fluoro derivative 14 with AgBF4 and DMSO, to give the geminal fluorohydrin system. (C) 2002 Elsevier Science Ltd. All rights reserved.