(2E,6E)-8-((tert-butyldiphenylsilyl)oxy)-3,7-dimethylocta-2,6-dien-1-ol | 127969-90-8

• 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: (2E,6E)-8-((tert-butyldiphenylsilyl)oxy)-3,7-dimethylocta-2,6-dien-1-ol
• 英文别名: (6E)-8-(tert-butyldiphenylsilyloxy)geraniol；(2E,6E)-8-[tert-butyl(diphenyl)silyl]oxy-3,7-dimethylocta-2,6-dien-1-ol
• CAS: 127969-90-8
• 化学式: C₂₆H₃₆O₂Si
• 分子量: 408.656
• InChiKey: VJCZCDXZSSPZTO-ORUUGEQNSA-N

物化性质

• 沸点：
  486.5±45.0 °C(Predicted)
• 密度：
  1.01±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.23
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2E,6E)-8-((tert-butyldiphenylsilyl)oxy)-3,7-dimethylocta-2,6-dien-1-ol 在 吡啶 、 咪唑 、 盐酸 、 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 正丁基锂 、 hexaammonium heptamolybdate tetrahydrate 、 四丁基氟化铵 、 双氧水 、 碘 、 sodium hexamethyldisilazane 、 4-甲基苯磺酸吡啶 、 magnesium 、 三苯基膦 、 六甲基二硅氮烷 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 乙二醇 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 78.41h， 生成 木香烃内酯
  参考文献：
  名称：

  Syntheses and Biological Evaluation of Costunolide, Parthenolide, and Their Fluorinated Analogues

  摘要：

  Inspired by the biosynthesis of sesquiterpene lactones (SLs), herein we report the asymmetric total synthesis of the germacrane ring (24). The synthetic strategy features a selective aldol reaction between beta,gamma-unsaturated chiral sulfonylamide 15a and aldehyde 13, as well as the intramolecular alpha-alkylation of sulfone 21 to construct a 10-membered carbocylic ring. The key intermediate 24 can be used to prepare the natural products costunolide and parthenolide (PTL), which are the key precursors for transformation into other SLs. Furthermore, the described synthetic sequences are amenable to the total synthesis of SL analogues, such as trifluoro-methylated analogues 32 and 45. Analogues 32 and 45 maintained high activities against a series of cancer cell lines compared to their parent PTL and costunolide, respectively. In addition, 32 showed enhanced tolerance to acidic media compared with PTL. To our surprise, PTL and 32 showed comparable half-lives in rat plasma and in the presence of human liver microsomes.

  DOI：

  10.1021/acs.jmedchem.5b00915
• 作为产物：
  描述：

  8-hydroxygeranyl acetate 在 咪唑 、 甲醇 、 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 (2E,6E)-8-((tert-butyldiphenylsilyl)oxy)-3,7-dimethylocta-2,6-dien-1-ol
  参考文献：
  名称：

  Synthesis of a Series of Promising Isobenzofuranones for the Treatment of Acute Mucositis Caused by Chemo- and Radiotherapy

  摘要：

  A small series of 3,5-dihydroxy-7-methoxy-3,6-dimethylisobenzofuran-1(3H)-one analogues of the immunosuppressant, mycophenolate mofelite (MMF), has been identified during a screening campaign as possible mediators to prevent mucositis. Herein, we present a general seven-step approach for the preparation of small molecule mycophenolate mofelite analogues, which are readily available for further biological evaluation in our mucositis model.

  DOI：

  10.1055/s-0033-1340060

文献信息

• Asymmetric Total Synthesis of Antiochic Acid
  作者：Yu-Jun Zhao、Teck-Peng Loh

  DOI：10.1021/ol800499p

  日期：2008.6.5

  The first asymmetric total synthesis of antiochic acid using bioinspired polyene cyclization strategy is described. Both good yield and good asymmetric induction were obtained.

  描述了使用生物启发的多烯环化策略进行的对乙酸的首次不对称全合成。获得了良好的收率和良好的不对称诱导。
• Synthesis and structure–activity studies of schweinfurthin B analogs: Evidence for the importance of a D-ring hydrogen bond donor in expression of differential cytotoxicity
  作者：Jeffrey D. Neighbors、Maya S. Salnikova、John A. Beutler、David F. Wiemer

  DOI：10.1016/j.bmc.2005.10.025

  日期：2006.3

  The synthesis and biological evaluation of several enantioenriched schweinfurthin B analogs were undertaken to develop structure-activity relationships and guide design of probes for their putative molecular target. The desired stilbenes contain a common left-half hexahydroxanthene ring system and an aromatic right-half with varied substituents. The synthesis involves penultimate Horner-Wadsworth-Emmons

  进行了几种对映体富集的Schweinfurthin B类似物的合成和生物学评估，以建立结构-活性关系并指导探针设计用于其推定的分子靶标。所需的对苯二酚含有常见的左半六氢氧杂蒽环系统和具有不同取代基的芳族右半。合成过程涉及将几种右半膦酸酯之一与包含3-脱氧schweinfurthin B左半醛的醛进行倒数第二次的Horner-Wadsworth-Emmons偶联。制备所需的膦酸酯和相应的对苯二甲酸酯，以及它们的细胞毒性图谱这些新化合物在美国国家癌症研究所的60细胞系抗癌筛选中进行了描述。这些类似物中的几种显示出与天然产物良好相关的细胞毒性模式，并且在各种细胞系中的活性差异约为10（3）。总之，这些测定结果表明该系统的芳族D-环上至少一个游离酚基对于区别细胞毒性的重要性。
• WO2007/97719
  申请人：——

  公开号：——

  公开（公告）日：——
• DAVIES, MARTIN J.;HESLIN, JULIE C.;MOODY, CHRISTOPHER J., J. CHEM. SOC. PERKIN TRANS. PT 1,(1989) N2, C. 2473-2484
  作者：DAVIES, MARTIN J.、HESLIN, JULIE C.、MOODY, CHRISTOPHER J.

  DOI：——

  日期：——
• Syntheses and Biological Evaluation of Costunolide, Parthenolide, and Their Fluorinated Analogues
  作者：Zhong-Jin Yang、Wei-Zhi Ge、Qiu-Ying Li、Yaxin Lu、Jian-Miao Gong、Bei-Jia Kuang、Xiaonan Xi、Haiting Wu、Quan Zhang、Yue Chen

  DOI：10.1021/acs.jmedchem.5b00915

  日期：2015.9.10

  Inspired by the biosynthesis of sesquiterpene lactones (SLs), herein we report the asymmetric total synthesis of the germacrane ring (24). The synthetic strategy features a selective aldol reaction between beta,gamma-unsaturated chiral sulfonylamide 15a and aldehyde 13, as well as the intramolecular alpha-alkylation of sulfone 21 to construct a 10-membered carbocylic ring. The key intermediate 24 can be used to prepare the natural products costunolide and parthenolide (PTL), which are the key precursors for transformation into other SLs. Furthermore, the described synthetic sequences are amenable to the total synthesis of SL analogues, such as trifluoro-methylated analogues 32 and 45. Analogues 32 and 45 maintained high activities against a series of cancer cell lines compared to their parent PTL and costunolide, respectively. In addition, 32 showed enhanced tolerance to acidic media compared with PTL. To our surprise, PTL and 32 showed comparable half-lives in rat plasma and in the presence of human liver microsomes.