10β-(trimethylsilyloxy)dihydroartemisinin | 140658-34-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 10β-(trimethylsilyloxy)dihydroartemisinin
• 英文别名: 10-O-(trimethylsilyl)dihydroartemisinin；10-O-(Trimethylsilyl)dihydroartemisinin；trimethyl-[[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]oxy]silane
• CAS: 140658-34-0
• 化学式: C₁₈H₃₂O₅Si
• 分子量: 356.535
• InChiKey: JUFSDODNZWADPX-VMAIWCPRSA-N

物化性质

• 沸点：
  375.5±42.0 °C(predicted)
• 密度：
  1.11±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.05
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  46.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  10β-(trimethylsilyloxy)dihydroartemisinin 在 三氟甲磺酸三甲基硅酯 、 barium(II) oxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 9.5h， 生成
  参考文献：
  名称：

  Antimalarial activity of new dihydroartemisinin derivatives. 5. Sugar analogs.

  摘要：

  A series of dihydroartemisinin derivatives containing a sugar moiety was prepared in the search for analogues with good water solubility and high antimalarial activity. The preparation of the new compounds were achieved by treatment of dihydroartemisinin (2) with chlorotrimethylsilane in pyridine solution at -10-degrees-C to give a nearly quantitative Yield of 10-0-(trimethylsilyl)dihydroartemisinin (3), which was then condensed with 1-hydroxypolyacetylated sugars 5 to give dihydroartemisinin derivatives 7a-d. Deacetylation of intermediates 7 gave the desired sugar derivatives 8. The resulting derivatives, tested in vitro against Plasmodium falciparum, were found to be more effective against W-2 than D-6 clones and were not cross-resistant with existing antimalarials. Trimethylsilylated compound 3 is more effective than derivatives 7a-d, which possess activity comparable to or better than that of artemisinin itself. Deacetylated compounds 8a-d were substantially less active than 7 in both cell lines. In P. berghei-infected mice, 7a-c showed 5/5, 2/5, and 3/5 cures, respectively, at 320 mg/kg per day X 3, whereas 7d showed no activity at the same dosage. However, 7d did prolong the life span in 3/5 of the infected mice at 640 mg/kg per day X 3 dose level. Trimethylsilylated compound 3 was also the most effective among the compounds studied, with 5/5 cures at 80 mg/kg per day X 3. The deacetylated sugar derivatives 8a-d showed only slight in vivo antimalarial activity.

  DOI：

  10.1021/jm00087a021
• 作为产物：
  描述：

  三甲基氯硅烷 、 dihydroartemisinin 以 吡啶 为溶剂， 反应 1.25h， 以76%的产率得到10β-(trimethylsilyloxy)dihydroartemisinin
  参考文献：
  名称：

  双氢青蒿素 - 10-α 青蒿琥酯的 C-10 酯和醚衍生物、正宗 10-β 青蒿琥酯的制备以及在 C-10 处具有潜在芳族插入基团的其他酯和醚衍生物的制备

  摘要：

  已经检查了提供抗疟药双氢青蒿素 (DHA, 2) 的新 C-10 酯和醚衍生物的反应的制备和立体化学方面。β-青蒿琥酯首次制备，与抗疟药α-青蒿琥酯相鉴别；后者在化学文摘和一些主要文献中被错误地指定为 β-差向异构体。通过 Schmidt、Mitsunobu 和 DCC 偶联程序、在 DMAP 存在下的酰化或以 BF3 作为催化剂的羟基活化，已经合成了带有潜在嵌入基团的新酯和醚衍生物。当 DHA 的羟基对酰化剂或 DCC 中间体中的活化羧基充当亲核试剂时，只能获得 α-酯。当羟基被激活以被亲核试剂取代时，如在 Schmidt 或 Mitsunobu 程序中，β-酯和 β-醚被完全或主要获得。一个例外是涉及 DHA 和 1- 和 2-萘酚的 Mitsunobu 程序，其中获得差向异构体的混合物；然而，当使用 Schmidt 程序时，会发生 β-芳基醚的独家形成，中间体三氯乙酰亚胺被 SnCl2

  DOI：

  10.1002/1099-0690(20021)2002:1<113::aid-ejoc113>3.0.co;2-n

文献信息

• C10-Modified Artemisinin Derivatives: Efficient Heme-Alkylating Agents
  作者：Sophie A.-L. Laurent、Anne Robert、Bernard Meunier

  DOI：10.1002/anie.200462556

  日期：2005.3.29
• C-10 Ester and Ether Derivatives of Dihydroartemisinin − 10-α Artesunate, Preparation of Authentic 10-β Artesunate, and of Other Ester and Ether Derivatives Bearing Potential Aromatic Intercalating Groups at C-10
  作者：Richard K. Haynes、Ho-Wai Chan、Man-Ki Cheung、Wai-Lun Lam、May-Kei Soo、Hing-Wo Tsang、Arnd Voerste、Ian D. Williams

  DOI：10.1002/1099-0690(20021)2002:1<113::aid-ejoc113>3.0.co;2-n

  日期：2002.1

  providing new C-10 ester and ether derivatives of the antimalarial drug dihydroartemisinin (DHA, 2) have been examined. β-Artesunate has been prepared for the first time, and has been differentiated from the antimalarial α-artesunate; the latter has been incorrectly designated as the β-epimer in Chemical Abstracts and some primary literature. New ester and ether derivatives bearing potential intercalating

  已经检查了提供抗疟药双氢青蒿素 (DHA, 2) 的新 C-10 酯和醚衍生物的反应的制备和立体化学方面。β-青蒿琥酯首次制备，与抗疟药α-青蒿琥酯相鉴别；后者在化学文摘和一些主要文献中被错误地指定为 β-差向异构体。通过 Schmidt、Mitsunobu 和 DCC 偶联程序、在 DMAP 存在下的酰化或以 BF3 作为催化剂的羟基活化，已经合成了带有潜在嵌入基团的新酯和醚衍生物。当 DHA 的羟基对酰化剂或 DCC 中间体中的活化羧基充当亲核试剂时，只能获得 α-酯。当羟基被激活以被亲核试剂取代时，如在 Schmidt 或 Mitsunobu 程序中，β-酯和 β-醚被完全或主要获得。一个例外是涉及 DHA 和 1- 和 2-萘酚的 Mitsunobu 程序，其中获得差向异构体的混合物；然而，当使用 Schmidt 程序时，会发生 β-芳基醚的独家形成，中间体三氯乙酰亚胺被 SnCl2
• Antimalarial activity of new dihydroartemisinin derivatives. 5. Sugar analogs.
  作者：Ai J. Lin、Liang Quan Li、Steven L. Andersen、Daniel L. Klayman

  DOI：10.1021/jm00087a021

  日期：1992.5

  A series of dihydroartemisinin derivatives containing a sugar moiety was prepared in the search for analogues with good water solubility and high antimalarial activity. The preparation of the new compounds were achieved by treatment of dihydroartemisinin (2) with chlorotrimethylsilane in pyridine solution at -10-degrees-C to give a nearly quantitative Yield of 10-0-(trimethylsilyl)dihydroartemisinin (3), which was then condensed with 1-hydroxypolyacetylated sugars 5 to give dihydroartemisinin derivatives 7a-d. Deacetylation of intermediates 7 gave the desired sugar derivatives 8. The resulting derivatives, tested in vitro against Plasmodium falciparum, were found to be more effective against W-2 than D-6 clones and were not cross-resistant with existing antimalarials. Trimethylsilylated compound 3 is more effective than derivatives 7a-d, which possess activity comparable to or better than that of artemisinin itself. Deacetylated compounds 8a-d were substantially less active than 7 in both cell lines. In P. berghei-infected mice, 7a-c showed 5/5, 2/5, and 3/5 cures, respectively, at 320 mg/kg per day X 3, whereas 7d showed no activity at the same dosage. However, 7d did prolong the life span in 3/5 of the infected mice at 640 mg/kg per day X 3 dose level. Trimethylsilylated compound 3 was also the most effective among the compounds studied, with 5/5 cures at 80 mg/kg per day X 3. The deacetylated sugar derivatives 8a-d showed only slight in vivo antimalarial activity.