10,11-Epoxy-3,7,11-trimethyl-2(E),6(E)-dodecadienyl tert-butyldimethylsilyl ether | 158897-41-7

• 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: 10,11-Epoxy-3,7,11-trimethyl-2(E),6(E)-dodecadienyl tert-butyldimethylsilyl ether
• 英文别名: tert-butyl(((2E,6E)-9-(3,3-dimethyloxiran-2-yl)-3,7-dimethylnona-2,6-dien-1-yl)oxy)dimethylsilane；tert-butyl-[(2E,6E)-9-(3,3-dimethyloxiran-2-yl)-3,7-dimethylnona-2,6-dienoxy]-dimethylsilane
• CAS: 158897-41-7
• 化学式: C₂₁H₄₀O₂Si
• 分子量: 352.633
• InChiKey: ZZEOHVGYNLZCOA-OVHYJKADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.64
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  21.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  10,11-Epoxy-3,7,11-trimethyl-2(E),6(E)-dodecadienyl tert-butyldimethylsilyl ether 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 10.0h， 以91%的产率得到(2E,6E)-10,11-环氧-3,7,11-三甲基-2,6-十二碳二烯-1-醇
  参考文献：
  名称：

  Synthesis of (6E)-8-Thia- and (14E)-13-Thia-2,3-oxidosqualene: Inhibitors of 2,3-Oxidosqualene-Lanosterol Cyclase

  摘要：

  Synthesis of (6E)-8-thia-2,3-oxidosqualene (22) and (14E)-13-thia-2,3-oxidosqualene (34) as inhibitors of 2,3-oxidosqualene-lanosterol cyclase are reported. Synthesis of 22 required the stereospecific generation of a vinyl sulfide. This was achieved by a new coupling of a benzenethiosulfonate (15) and a lithiated vinyl iodide (18). Synthesis of 34 involved similar coupling of benzenethiosulfonate 29 with lithium reagent obtained from vinyl iodide 33. The required (E)-vinyl iodides 18 and 33 were prepared by zirconium-catalyzed carboalumination of 4-pentyn-1-ol, (16) and 2,6-dimethyl-2(E),6(E)-dien-10-yne (32) respectively. Both 22 and 34 inhibited 2,3-oxidosqualene-lanosterol cyclase from Candida albicans with IC50 values of 0.68 and 45 mu M, respectively.

  DOI：

  10.1021/jo00098a048
• 作为产物：
  描述：

  反式,反式-金合欢醇 在 咪唑 、 N-溴代丁二酰亚胺(NBS) 、 水 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 7.5h， 生成 10,11-Epoxy-3,7,11-trimethyl-2(E),6(E)-dodecadienyl tert-butyldimethylsilyl ether
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS FOR THE PREVENTION AND/OR TREATMENT OF MITOCHONDRIAL DISEASE, INCLUDING FRIEDREICH'S ATAXIA
  [FR] COMPOSITIONS ET MÉTHODES POUR LA PRÉVENTION ET/OU LE TRAITEMENT D'UNE MALADIE MITOCHONDRIALE, NOTAMMENT L'ATAXIE DE FRIEDREICH

  摘要：

  该披露提供了治疗化合物、组合物（例如治疗剂或药物）和方法，用于预防或治疗哺乳动物主体中的线粒体疾病，如弗里德赖希共济失调，减少与线粒体疾病（例如弗里德赖希共济失调）相关的风险因素、症状和/或症状，并/或减少线粒体疾病（例如弗里德赖希共济失调）的发生可能性或严重程度。该披露还提供了用于生产上述治疗组合物的新型中间体。在某些情况下，这些中间体本身可能是治疗剂或治疗剂的前药（例如治疗化合物的还原形式）。

  公开号：

  WO2021202986A1

文献信息

• Farnesyl chain modification of squalene synthase inhibitor benzylfarnesylamine: Conversion to the terminal bis(trifluoromethyl) derivative
  作者：Charles F Jewell、John Brinkman、Russell C Petter、James R Wareing

  DOI：10.1016/s0040-4020(01)89661-7

  日期：1994.3

  Potent squalene synthase inhibitor 1 was converted to the bis(trifluoromethyl) analog 14 in 11% overall yield for 9 steps. The amine nitrogen of 1 was protected with the 2-(trimethylsilyl)ethoxycarbonyl (TEOC) protecting group. The 10,11 olefin was selectively epoxidized, cleaved and converted to the phosphonium salt 6. The ylid from 6 underwent a Wittig condensation with hexafluoroacetone to give

  将强力角鲨烯合酶抑制剂1以11％的总收率转化为双（三氟甲基）类似物14，历时9个步骤。的胺氮1是用2-（三甲基硅烷基）乙氧基羰基（TEOC）保护基团保护。将10，11烯烃选择性地环氧化，裂解并转化为the盐6。将来自6的类化合物与六氟丙酮进行Wittig缩合反应，得到含TEOC的烯烃8。如果不将法呢基链的10,11烯烃异构化为E-9,10烯烃，则四丁基氟化铵或HF不能除去TEOC基团。的双（三氟甲基）烯烃8对酸性或碱性条件非常敏感。然而，发现BF 3 ·Et 2 O可以除去TEOC基团而没有不希望的异构化得到14。
• Synthesis of (6E)-8-Thia- and (14E)-13-Thia-2,3-oxidosqualene: Inhibitors of 2,3-Oxidosqualene-Lanosterol Cyclase
  作者：Yi Feng Zheng、Allan C. Oehlschlager、Peter G. Hartman

  DOI：10.1021/jo00098a048

  日期：1994.9

  Synthesis of (6E)-8-thia-2,3-oxidosqualene (22) and (14E)-13-thia-2,3-oxidosqualene (34) as inhibitors of 2,3-oxidosqualene-lanosterol cyclase are reported. Synthesis of 22 required the stereospecific generation of a vinyl sulfide. This was achieved by a new coupling of a benzenethiosulfonate (15) and a lithiated vinyl iodide (18). Synthesis of 34 involved similar coupling of benzenethiosulfonate 29 with lithium reagent obtained from vinyl iodide 33. The required (E)-vinyl iodides 18 and 33 were prepared by zirconium-catalyzed carboalumination of 4-pentyn-1-ol, (16) and 2,6-dimethyl-2(E),6(E)-dien-10-yne (32) respectively. Both 22 and 34 inhibited 2,3-oxidosqualene-lanosterol cyclase from Candida albicans with IC50 values of 0.68 and 45 mu M, respectively.
• [EN] COMPOSITIONS AND METHODS FOR THE PREVENTION AND/OR TREATMENT OF MITOCHONDRIAL DISEASE, INCLUDING FRIEDREICH'S ATAXIA<br/>[FR] COMPOSITIONS ET MÉTHODES POUR LA PRÉVENTION ET/OU LE TRAITEMENT D'UNE MALADIE MITOCHONDRIALE, NOTAMMENT L'ATAXIE DE FRIEDREICH
  申请人：STEALTH BIOTHERAPEUTICS CORP

  公开号：WO2021202986A1

  公开（公告）日：2021-10-07

  The disclosure provides therapeutic compounds, compositions (e.g., therapeutic agents or medicaments) and methods for preventing or treating mitochondrial disease such as Friedreich's ataxia in a mammalian subject, reducing risk factors, signs and/or symptoms associated with mitochondrial disease, such as Friedreich's ataxia, and/or reducing the likelihood or severity of mitochondrial disease such as Friedreich's ataxia. The disclosure further provides novel intermediates for the production of said therapeutic compositions. In some instances, the intermediates may themselves by therapeutic agents or prodrugs of therapeutic agents (e.g. reduced forms of the therapeutic compounds).

  该披露提供了治疗化合物、组合物（例如治疗剂或药物）和方法，用于预防或治疗哺乳动物主体中的线粒体疾病，如弗里德赖希共济失调，减少与线粒体疾病（例如弗里德赖希共济失调）相关的风险因素、症状和/或症状，并/或减少线粒体疾病（例如弗里德赖希共济失调）的发生可能性或严重程度。该披露还提供了用于生产上述治疗组合物的新型中间体。在某些情况下，这些中间体本身可能是治疗剂或治疗剂的前药（例如治疗化合物的还原形式）。