isobu-diol | 676620-16-9

• 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: isobu-diol
• 英文别名: 3-[(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]-2-[[(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]methyl]propane-1,2-diol
• CAS: 676620-16-9
• 化学式: C₃₄H₅₄O₁₀
• 分子量: 622.797
• InChiKey: TXRIYYDFUNWOTM-RQOGQRONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  44
• 可旋转键数：
  5
• 环数：
  10.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  10

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	dihydroartemisinin	71939-50-9	C15H24O5	284.353
  ——	(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-10-[2-[[(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]methyl]prop-2-enyl]-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane	673500-71-5	C34H52O8	588.782
  ——	dihydroartemisinin acetate	75887-51-3	C17H26O6	326.39

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	LH-isobudiol-acetal-form	941713-20-8	C35H54O10	634.808
  ——	WC-isobudiol-ketal-CB	941713-23-1	C38H58O10	674.873
  ——	LW-isobudiol-ketal-4THP	941713-19-5	C39H60O11	704.899
  ——	LH-isobudiol-ketal-4-one	941713-21-9	C40H60O11	716.91
  ——	1,3-bis[(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]propan-2-one	676620-25-0	C33H50O9	590.755
  ——	1-[4-[(4-fluorophenyl)methoxy]but-2-ynoxy]-3-[(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]-2-[[(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]methyl]propan-2-ol	1011470-59-9	C45H63FO11	798.987
  ——	ASK-isobudiol-C(O)Ph	941713-30-0	C41H58O11	726.905
  ——	N-methyl-3,3-bis[[(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]methyl]-1,4-dioxa-8-azaspiro[4.5]decane-8-carboxamide	1011470-54-4	C41H64N2O11	760.966
  ——	LW-isobudiol-ketal-pipC(O)OEt	941713-26-4	C42H65NO12	775.978
  ——	[3,3-bis[[(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]methyl]-1,4-dioxa-8-azaspiro[4.5]decan-8-yl]-phenylmethanone	1011470-51-1	C46H65NO11	808.022

反应信息

• 作为反应物：
  描述：

  isobu-diol 在 ruthenium trichloride 、 sodium periodate 作用下， 以81%的产率得到1,3-bis[(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]propan-2-one
  参考文献：
  名称：

  Malaria-Infected Mice Are Cured by Oral Administration of New Artemisinin Derivatives

  摘要：

  In four or five chemical steps from the 1,2,4-trioxane artemisinin, a new series of 23 trioxane dimers has been prepared. Eleven of these new trioxane dimers cure malaria-infected mice via oral dosing at 3 x 30 mg/kg. The clinically used trioxane drug sodium artesunate prolonged mouse average survival to 7.2 days with this oral dose regimen. In comparison, animals receiving no drug die typically on day 6-7 postinfection. At only 3 x 10 mg/kg oral dosing, seven dimers prolong the lifetime of malaria-infected mice to days 14-17, more than double the chemotherapeutic effect of sodium artesunate. Ten new trioxane dimers at only a single oral dose of 30 mg/kg prolong mouse average survival to days 8.7-13.7, and this effect is comparable to that of the fully synthetic trioxolane drug development candidate OZ277, which is in phase 11 clinical trials.

  DOI：

  10.1021/jm701168h
• 作为产物：
  描述：

  dihydroartemisinin acetate 在 四氧化锇 、 四氯化锡 、 N-甲基吗啉氧化物 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 25.5h， 生成 isobu-diol
  参考文献：
  名称：

  青蒿素衍生的二聚体、三聚体和树枝状聚合物的合成：研究它们的抗疟和抗病毒活性，包括推定的作用机制

  摘要：

  生物活性化合物的二聚体、三聚体和树枝状聚合物的生成是最近为发现新的有效候选药物而开发的一种方法。在此，我们展示了新的青蒿素衍生二聚体和树枝状聚合物的合成，并研究了它们对疟原虫恶性疟原虫3D7 株和人巨细胞病毒 (HCMV) 的作用。二聚体7是最活跃的化合物（EC 50 1.4Ñ米）在抗疟疾功效方面，是更有效的比标准药物双氢青蒿素（EC 50 2.4Ñ米），artesunic酸（EC 50 8.9Ñ米）和氯喹（EC 50为9.8N米）。Trimer 4作为体外抗 HCMV 复制中最具活性的药物脱颖而出，其 EC 50值为 0.026 μm，比两种参考药物更昔洛韦 (EC 50 2.60 μm ) 和青蒿琥酯 (EC 50 5.41 ) 的活性更高μ米）。此外，青蒿素衍生的二聚体13和三聚体15首次固定在 TOYOPEARL AF-Amino-650M 珠上，并用于使用 HCMV 感染的原代人

  DOI：

  10.1002/chem.201800729

文献信息

• WO2007/67333
  申请人：——

  公开号：——

  公开（公告）日：——
• Malaria-Infected Mice Are Cured by a Single Dose of Novel Artemisinin Derivatives
  作者：Gary H. Posner、Ik-Hyeon Paik、Wonsuk Chang、Kristina Borstnik、Sandra Sinishtaj、Andrew S. Rosenthal、Theresa A. Shapiro

  DOI：10.1021/jm070149m

  日期：2007.5.1

  We disclose here for the first time the curative activity of a new generation of trioxane dimers, designed logically and prepared easily from the natural trioxane artemisinin in only four or five chemical steps that would be easily accomplished also on a manufacturing scale. Four of these trioxane dimers cure malaria-infected mice after only a single subcutaneous dose, and two other dimers cure after three oral doses.
• Malaria-Infected Mice Are Cured by Oral Administration of New Artemisinin Derivatives
  作者：Gary H. Posner、Wonsuk Chang、Lindsey Hess、Lauren Woodard、Sandra Sinishtaj、Aimee R. Usera、William Maio、Andrew S. Rosenthal、Alvin S. Kalinda、John G. D’Angelo、Kimberly S. Petersen、Remo Stohler、Jacques Chollet、Josefina Santo-Tomas、Christopher Snyder、Matthias Rottmann、Sergio Wittlin、Reto Brun、Theresa A. Shapiro

  DOI：10.1021/jm701168h

  日期：2008.2.1

  In four or five chemical steps from the 1,2,4-trioxane artemisinin, a new series of 23 trioxane dimers has been prepared. Eleven of these new trioxane dimers cure malaria-infected mice via oral dosing at 3 x 30 mg/kg. The clinically used trioxane drug sodium artesunate prolonged mouse average survival to 7.2 days with this oral dose regimen. In comparison, animals receiving no drug die typically on day 6-7 postinfection. At only 3 x 10 mg/kg oral dosing, seven dimers prolong the lifetime of malaria-infected mice to days 14-17, more than double the chemotherapeutic effect of sodium artesunate. Ten new trioxane dimers at only a single oral dose of 30 mg/kg prolong mouse average survival to days 8.7-13.7, and this effect is comparable to that of the fully synthetic trioxolane drug development candidate OZ277, which is in phase 11 clinical trials.
• Synthesis of Artemisinin-Derived Dimers, Trimers and Dendrimers: Investigation of Their Antimalarial and Antiviral Activities Including Putative Mechanisms of Action
  作者：Tony Fröhlich、Friedrich Hahn、Lucid Belmudes、Maria Leidenberger、Oliver Friedrich、Barbara Kappes、Yohann Couté、Manfred Marschall、Svetlana B. Tsogoeva

  DOI：10.1002/chem.201800729

  日期：2018.6.7

  both immobilized on TOYOPEARL AF‐Amino‐650M beads and used for mass spectrometry‐based target identification experiments using total lysates of HCMV‐infected primary human fibroblasts. Two major groups of novel target candidates, namely cytoskeletal and mitochondrial proteins were obtained. Two putatively compound‐binding viral proteins, namely major capsid protein (MCP) and envelope glycoprotein pUL132

  生物活性化合物的二聚体、三聚体和树枝状聚合物的生成是最近为发现新的有效候选药物而开发的一种方法。在此，我们展示了新的青蒿素衍生二聚体和树枝状聚合物的合成，并研究了它们对疟原虫恶性疟原虫3D7 株和人巨细胞病毒 (HCMV) 的作用。二聚体7是最活跃的化合物（EC 50 1.4Ñ米）在抗疟疾功效方面，是更有效的比标准药物双氢青蒿素（EC 50 2.4Ñ米），artesunic酸（EC 50 8.9Ñ米）和氯喹（EC 50为9.8N米）。Trimer 4作为体外抗 HCMV 复制中最具活性的药物脱颖而出，其 EC 50值为 0.026 μm，比两种参考药物更昔洛韦 (EC 50 2.60 μm ) 和青蒿琥酯 (EC 50 5.41 ) 的活性更高μ米）。此外，青蒿素衍生的二聚体13和三聚体15首次固定在 TOYOPEARL AF-Amino-650M 珠上，并用于使用 HCMV 感染的原代人