dehydroaltenusin | 34279-44-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: dehydroaltenusin
• 英文别名: 3,7-dihydroxy-9-methoxy-4a-methyl-4aH-benzo[c]chromene-2,6-dione；3,7-Dihydroxy-9-methoxy-4a-methyl-4aH-benzo[c]chromen-2,6-dion；(+/-)-Dehydroaltenusin；6H-Dibenzo[b,d]pyran-2,6(4aH)-dione,3,7-dihydroxy-9-methoxy-4a-methyl-, (4aS)-；3,7-dihydroxy-9-methoxy-4a-methylbenzo[c]chromene-2,6-dione
• CAS: 34279-44-2
• 化学式: C₁₅H₁₂O₆
• 分子量: 288.257
• InChiKey: YWYZLBQRCUAQAV-UHFFFAOYSA-N

物化性质

• 熔点：
  189-190 °C
• 沸点：
  654.0±55.0 °C(Predicted)
• 密度：
  1.54±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-乙酰基-L-半胱氨酸甲酯 、 dehydroaltenusin 以 甲醇 、 水 为溶剂， 反应 0.5h， 生成 2'-{[2-(acetylamino)-3-methoxy-3-oxopropyl]-sulfanyl}-3,3',4'-trihydroxy-6'-methyl-5-methoxybiphenyl-2-carboxylic acid 、 3'-{[2-(acetylamino)-3-methoxy-3-oxopropyl]sulfanyl}-3,4',5'-trihydroxy-2'-methyl-5-methoxybiphenyl-2-carboxylic acid
  参考文献：
  名称：

  脱氢altenusin衍生物作为选择性DNA聚合酶α抑制剂的合成及其构效关系

  摘要：

  在这里，我们描述了脱氢altenusin衍生物作为哺乳动物DNA聚合酶α的抑制剂的合成和构效关系。我们新合成了在侧链或苯醌部分上修饰的九种脱氢altenusin衍生物。我们还实现了脱甲基altenusin和脱甲基altenusin的新合成，这是链格孢菌的代谢产物。或Talaromyces flavus。在所有合成的衍生物中，脱甲氧基脱氢altenusin是DNA聚合酶α的最具选择性的抑制剂。该Ø羟基p-苯醌（2-羟基环己-2,5-二烯酮）部分对于抑制DNA聚合酶至关重要。脱氢altenusin的5位取代对抑制效能很重要。因为脱氢altenusin与N-乙酰半胱氨酸甲酯在邻-羟基-对苯醌醌部分缀合，所以DNA聚合酶α的一个或多个半胱氨酸残基可以充当该化合物的靶标。

  DOI：

  10.1016/j.bmc.2009.08.051
• 作为产物：
  描述：

  三氟甲烷磺酸7-甲氧基-2,2-二甲基-4-氧代-4H-1,3-苯并二氧杂环己-5-基酯 在 四(三苯基膦)钯 氢氧化钾 、 potassium phosphate 、 三氯化铁 、 potassium bromide 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 23.34h， 生成 dehydroaltenusin
  参考文献：
  名称：

  Total synthesis of dehydroaltenusin

  摘要：

  The first total synthesis of dehydroaltenusin, a natural enzyme inhibitor, is described. The key step involves Suzuki-coupling reaction of an aryl triflate prepared from 2,4,6-trihydroxybenzoic acid with a catechol-derived boronic acid or boronic ester. The synthetic product was evaluated as a potent inhibitor against eukaryotic DNA polymerase a and other DNA polymerases. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2004.05.017

文献信息

• Total Synthesis of Dehydroaltenuene A. Revision of the Structure and Total Synthesis of Dihydroaltenuene B
  作者：Martina Altemöller、Joachim Podlech

  DOI：10.1021/np900265q

  日期：2009.7.24

  Total synthesis of alternaria toxins starting from previously synthesized altenuene (3) and isoaltenuene (4) is described. Dihydroaltenuene B (9) was prepared by hydrogenation of 3, and the non-natural epimer 3-epi-dihydroaltenuene A was obtained analogously from 4. Inspection of the spectroscopic data for 9 revealed that the originally proposed structure was in error. A revised structure (11), unambiguously

  描述了从先前合成的altenuene（3）和isoaltenuene（4）开始的交链孢霉毒素的全合成。通过氢化3制备二氢铝烯B（9），类似地从4获得非天然差向异构体3- Epi -dihydroaltenueneA 。检查9的光谱数据表明，最初提出的结构有误。本文报道了经全合成明确证实的修饰结构（11）。在乙酸钯（II）的存在下用氧气氧化4导致形成脱氢铝烯A（8），而在相同条件下将3氧化，则生成ent- dehydroaltenuene B（ent - 9）。氧化4与锰（IV）氧化物布置dehydroaltenusin（12），尽管在低的产率得到仅不纯的物质。
• Rosett et al., Biochemical Journal, 1957, vol. 67, p. 390,393
  作者：Rosett et al.

  DOI：——

  日期：——
• Precise structural elucidation of dehydroaltenusin, a specific inhibitor of mammalian DNA polymerase α
  作者：Shinji Kamisuki、Shunya Takahashi、Yoshiyuki Mizushina、Kengo Sakaguchi、Tadashi Nakata、Fumio Sugawara

  DOI：10.1016/j.bmc.2004.07.047

  日期：2004.10

  The X-ray crystal structure of dehydroaltenusin, a specific inhibitor of mammalian DNA polymerase alpha, has previously been reported. We show that dehydroaltenusin exists in an equilibrium mixture of two tautomers possessing gamma-lactone or delta-lactone in polar solvents by NMR experiments. Acetylation of dehydroaltenusin afforded two types of diacetates and two types of monoacetate, possessing gamma-lactone or delta-lactone, respectively. The inhibitory activities of these acetate derivatives against DNA polymerase alpha were all much weaker than that of dehydroaltenusin. (C) 2004 Elsevier Ltd. All rights reserved.
• Synthesis and structure–activity relationships of dehydroaltenusin derivatives as selective DNA polymerase α inhibitors
  作者：Kouji Kuramochi、Keishi Fukudome、Isoko Kuriyama、Toshifumi Takeuchi、Yoshihiro Sato、Shinji Kamisuki、Kazunori Tsubaki、Fumio Sugawara、Hiromi Yoshida、Yoshiyuki Mizushina

  DOI：10.1016/j.bmc.2009.08.051

  日期：2009.10

  Herein, we describe the synthesis and structure–activity relationships of dehydroaltenusin derivatives as inhibitors of a mammalian DNA polymerase α. We have newly synthesized nine dehydroaltenusin derivatives modified at the side chains or benzoquinone moiety. We also achieved the first synthesis of desmethylaltenusin and desmethyldehydroaltenusin, metabolites of Alternaria sp. or Talaromyces flavus

  在这里，我们描述了脱氢altenusin衍生物作为哺乳动物DNA聚合酶α的抑制剂的合成和构效关系。我们新合成了在侧链或苯醌部分上修饰的九种脱氢altenusin衍生物。我们还实现了脱甲基altenusin和脱甲基altenusin的新合成，这是链格孢菌的代谢产物。或Talaromyces flavus。在所有合成的衍生物中，脱甲氧基脱氢altenusin是DNA聚合酶α的最具选择性的抑制剂。该Ø羟基p-苯醌（2-羟基环己-2,5-二烯酮）部分对于抑制DNA聚合酶至关重要。脱氢altenusin的5位取代对抑制效能很重要。因为脱氢altenusin与N-乙酰半胱氨酸甲酯在邻-羟基-对苯醌醌部分缀合，所以DNA聚合酶α的一个或多个半胱氨酸残基可以充当该化合物的靶标。
• Total synthesis of dehydroaltenusin
  作者：Shinji Kamisuki、Shunya Takahashi、Yoshiyuki Mizushina、Shinya Hanashima、Kouji Kuramochi、Susumu Kobayashi、Kengo Sakaguchi、Tadashi Nakata、Fumio Sugawara

  DOI：10.1016/j.tet.2004.05.017

  日期：2004.6

  The first total synthesis of dehydroaltenusin, a natural enzyme inhibitor, is described. The key step involves Suzuki-coupling reaction of an aryl triflate prepared from 2,4,6-trihydroxybenzoic acid with a catechol-derived boronic acid or boronic ester. The synthetic product was evaluated as a potent inhibitor against eukaryotic DNA polymerase a and other DNA polymerases. (C) 2004 Elsevier Ltd. All rights reserved.

表征谱图