3-Vinyl-7,11-dimethyldodeca-2(Z),6(E),10-trien-1-ol | 157327-76-9

• 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: 3-Vinyl-7,11-dimethyldodeca-2(Z),6(E),10-trien-1-ol
• 英文别名: 13-methylidenefarnesol；3-vinylfarnesol；(2Z,6E)-3-ethenyl-7,11-dimethyldodeca-2,6,10-trien-1-ol
• CAS: 157327-76-9
• 化学式: C₁₆H₂₆O
• 分子量: 234.382
• InChiKey: GBAWXFFNMZHJIH-NCZFFCEISA-N

物化性质

• 沸点：
  340.3±11.0 °C(predicted)
• 密度：
  0.882±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  17
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-Vinyl-7,11-dimethyldodeca-2(Z),6(E),10-trien-1-ol 在 manganese(IV) oxide 、 sodium borotritide 作用下， 以 甲醇 、 正己烷 为溶剂， 反应 5.5h， 生成 1-[3H]-3-vinyl-7,11-dimethyldodeca-2(Z),6(E),10-trien-1-ol
  参考文献：
  名称：

  新型法尼醇和香叶基香叶醇类似物：潜在的一类针对蛋白质异戊二烯化的新型抗癌剂。

  摘要：

  蛋白法呢基转移酶（FTase）是负责蛋白法呢基化的酶，已成为合理设计癌症化学治疗剂的关键目标。本文显示某些新颖的异戊二烯基二磷酸类似物是哺乳动物FTase的有效抑制剂。此外，这些化合物中的两种的醇前体能够阻止ras转化细胞的锚定非依赖性生长。虽然3-烯丙基法呢醇抑制蛋白质法呢基化，但是3-乙烯基法呢醇反而导致具有3-乙烯基法呢基基团的蛋白质的异常烯丙基化。以类似的方式，3-烯丙基香叶基香叶醇充当蛋白香叶基香叶基化的高度特异性抑制剂，而3-乙烯基香叶基香叶醇恢复细胞中的蛋白质香叶基香叶基化。这项研究表明，某些异戊二烯醇类似物可以通过新的前药机制原位充当异戊二烯基转移酶抑制剂。这些类似物可能被证明是研究相对于法呢基化抑制香叶基香叶基化的治疗结果的有价值的工具。此外，3-乙烯醇类似物可以通过不涉及异戊二烯基转移酶抑制的机制抑制转化的细胞生长。

  DOI：

  10.1021/jm9902786
• 作为产物：
  描述：

  香叶基溴 在 Pd(AsPh₃)2 copper(l) iodide 、 正丁基锂 、 双(三甲基硅烷基)氨基钾 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲苯 为溶剂， 生成 3-Vinyl-7,11-dimethyldodeca-2(Z),6(E),10-trien-1-ol
  参考文献：
  名称：

  Inhibition of Glucose- and Calcium-Induced Insulin Secretion from βTC3 Cells by Novel Inhibitors of Protein Isoprenylation

  摘要：

  大多数低分子量的 G 蛋白在其 C 端半胱氨酸处经历了一系列翻译后修饰步骤，如异戊烯化，这似乎是将修饰后的蛋白运输到膜位点与其各自的效应蛋白相互作用的关键。洛伐他汀是甲羟戊酸的抑制剂，因此也是异戊烯生物合成的抑制剂，我们之前利用洛伐他汀证明了蛋白质异戊烯化对正常大鼠胰岛的生理性胰岛素分泌至关重要。在这里，我们使用了更具选择性的蛋白质前炔化合成抑制剂来研究它们对葡萄糖和钙介导的βTC3细胞胰岛素分泌的影响。抑制和/或调节蛋白法尼酰转移酶的 3-烯丙基和乙烯基法尼醇都能显著（80-95%）抑制这些细胞在葡萄糖和 KCl 刺激下分泌胰岛素。与此类似，针对蛋白质香叶基化的试剂香叶基烯丙基和乙烯基形式的香叶基炔醇也能减弱葡萄糖和氯化钾引起的胰岛素分泌。此外，法尼基化蛋白的天然抑制剂 manumycin A 和拟肽抑制剂 geranylgeranyl 转移酶抑制剂-2147（GGTI-2147）也能在相当程度上抑制葡萄糖和氯化钾诱导的胰岛素分泌。用 3-vinylfarnesol 或 3-vinyl geranylgeraniol 处理 βTC3 细胞会导致未肾上腺素化的蛋白质在细胞膜部分积累。这些数据进一步支持了我们最初的观点，即抑制小分子量 G 蛋白的异戊烯化可能会阻碍它们与其可能的效应物之间的相互作用，而这可能是生理性胰岛素分泌所必需的。

  DOI：

  10.1124/jpet.102.036160

文献信息

• A Pd(0)-catalyzed route to 13-methylidenefarnesyl diphosphate
  作者：Richard A. Gibbs、Usha Krishnan

  DOI：10.1016/s0040-4039(00)77157-7

  日期：1994.4

  The synthesis of the novel FPP analog 13-methylidenefarnesyl diphosphate 2 is described. The key step in the synthetic sequence involved the stereoselective coupling of enol triflate 8 with vinyltributyltin using Pd(AsPh(3))(2) and CuI as catalysts to afford primarily the desired cis-divinylester 7. It is also demonstrated that other 3-substituted famesyl analogs can be prepared by this Pd(0)catalyzed route.
• A Stereoselective Palladium/Copper-Catalyzed Route to Isoprenoids: Synthesis and Biological Evaluation of 13-Methylidenefarnesyl Diphosphate
  作者：Richard A. Gibbs、Usha Krishnan、Julia M. Dolence、C. Dale Poulter

  DOI：10.1021/jo00129a023

  日期：1995.12

  The novel farnesyl diphosphate (FPP) analog 13-methylidenefarnesyl diphosphate (3-VFPP, 4) was designed as a potential mechanism-based inhibitor of the FPP-utilizing enzyme protein-farnesyl transferase (PFTase). A six-step stereoselective route to 3-VFPP is described. The key step in the synthetic sequence involved the stereoselective coupling of vinyl triflate 16 with vinyltributyltin using Pd(AsPh(3))(2) and CuI as catalysts to afford primarily the desired (Z)-divinyl ester 15. It was also demonstrated that other 3-substituted farnesyl analogs can be prepared in a highly stereoselective manner by this Pd(0)/CuI-catalyzed route. The presence of CuI significantly increases the stereoselectivity of the coupling reaction, and a possible mechanistic rationale for this observation is presented. Biological evaluation of 3-VFPP demonstrates that it is not a time-dependent inhibitor of recombinant yeast PFTase. Instead, 3-VFPP is an alternative substrate for this. enzyme that exhibits a K-m comparable to FPP but a k(cat) significantly lower than the natural substrate.
• Synthesis and evaluation of 3- and 7-substituted geranylgeranyl pyrophosphate analogs
  作者：Michelle Maynor、Sarah A. Scott、Emily L. Rickert、Richard A. Gibbs

  DOI：10.1016/j.bmcl.2008.02.014

  日期：2008.3

  Protein prenyl transferases have been a focus of anti-cancer drug discovery in recent years due to their roles in post-translational modi. cation of small GTP binding proteins. Attention is now turning to the development of GGTase I inhibitors. Here, we present the synthesis and biological evaluation of four GGPP analogs versus mammalian GGTase I and the discovery that 7-allyl GGPP is a surprisingly efficient GGTase I substrate. (C) 2008 Elsevier Ltd. All rights reserved.
• Novel Farnesol and Geranylgeraniol Analogues:  A Potential New Class of Anticancer Agents Directed against Protein Prenylation
  作者：Barbara S. Gibbs、Todd J. Zahn、YongQi Mu、Judith S. Sebolt-Leopold、Richard A. Gibbs

  DOI：10.1021/jm9902786

  日期：1999.9.1

  ras-transformed cells. While 3-allylfarnesol inhibits protein farnesylation, 3-vinylfarnesol instead leads to abnormal prenylation of proteins with the 3-vinylfarnesyl group. In a similar manner, 3-allylgeranylgeraniol acts as a highly specific inhibitor of protein geranylgeranylation, while 3-vinylgeranylgeraniol restores protein geranylgeranylation in cells. This study indicates that certain prenyl alcohol

  蛋白法呢基转移酶（FTase）是负责蛋白法呢基化的酶，已成为合理设计癌症化学治疗剂的关键目标。本文显示某些新颖的异戊二烯基二磷酸类似物是哺乳动物FTase的有效抑制剂。此外，这些化合物中的两种的醇前体能够阻止ras转化细胞的锚定非依赖性生长。虽然3-烯丙基法呢醇抑制蛋白质法呢基化，但是3-乙烯基法呢醇反而导致具有3-乙烯基法呢基基团的蛋白质的异常烯丙基化。以类似的方式，3-烯丙基香叶基香叶醇充当蛋白香叶基香叶基化的高度特异性抑制剂，而3-乙烯基香叶基香叶醇恢复细胞中的蛋白质香叶基香叶基化。这项研究表明，某些异戊二烯醇类似物可以通过新的前药机制原位充当异戊二烯基转移酶抑制剂。这些类似物可能被证明是研究相对于法呢基化抑制香叶基香叶基化的治疗结果的有价值的工具。此外，3-乙烯醇类似物可以通过不涉及异戊二烯基转移酶抑制的机制抑制转化的细胞生长。
• Inhibition of Glucose- and Calcium-Induced Insulin Secretion from βTC3 Cells by Novel Inhibitors of Protein Isoprenylation
  作者：Rajesh Amin、Hai-Qing Chen、Marie Tannous、Richard Gibbs、Anjaneyulu Kowluru

  DOI：10.1124/jpet.102.036160

  日期：2002.10.1

  The majority of low molecular weight G proteins undergoes a series of post-translational modification steps, e.g., isoprenylation, at their C-terminal cysteine, which seem to be critical for the transport of the modified proteins to the membrane sites for interaction with their respective effector proteins. Using lovastatin, an inhibitor of mevalonic acid, and hence, isoprenoid biosynthesis, we demonstrated previously that protein isoprenylation is critical for physiological insulin secretion from normal rat islets. Herein, we used more selective synthetic inhibitors of protein prenylation to examine their effects on glucose- and calcium-mediated insulin secretion from βTC3 cells. Both 3-allyl- and vinylfarnesols, which inhibit and/or modulate protein farnesyl transferases, significantly (80–95%) inhibited glucose- and KCl-stimulated insulin secretion from these cells. In a similar manner, the allyl and vinyl forms of geranylgeraniol, reagents targeted toward protein geranylation, attenuated insulin secretion elicited by glucose and KCl. Furthermore, manumycin A, a natural inhibitor of protein farnesylation, and geranylgeranyl transferase inhibitor-2147 (GGTI-2147), a peptidomimetic inhibitor of protein geranylgeranylation, also inhibited glucose- and KCl-induced insulin secretion to comparable degrees. Treatment of βTC3 cells with either 3-vinylfarnesol or 3-vinyl geranylgeraniol resulted in accumulation of unprenylated proteins in the cytosolic fraction. These data further support our original formulation that inhibition of isoprenylation of small molecular weight G proteins might impede their interaction with their putative effectors, which may be required for physiological insulin secretion.

  大多数低分子量的 G 蛋白在其 C 端半胱氨酸处经历了一系列翻译后修饰步骤，如异戊烯化，这似乎是将修饰后的蛋白运输到膜位点与其各自的效应蛋白相互作用的关键。洛伐他汀是甲羟戊酸的抑制剂，因此也是异戊烯生物合成的抑制剂，我们之前利用洛伐他汀证明了蛋白质异戊烯化对正常大鼠胰岛的生理性胰岛素分泌至关重要。在这里，我们使用了更具选择性的蛋白质前炔化合成抑制剂来研究它们对葡萄糖和钙介导的βTC3细胞胰岛素分泌的影响。抑制和/或调节蛋白法尼酰转移酶的 3-烯丙基和乙烯基法尼醇都能显著（80-95%）抑制这些细胞在葡萄糖和 KCl 刺激下分泌胰岛素。与此类似，针对蛋白质香叶基化的试剂香叶基烯丙基和乙烯基形式的香叶基炔醇也能减弱葡萄糖和氯化钾引起的胰岛素分泌。此外，法尼基化蛋白的天然抑制剂 manumycin A 和拟肽抑制剂 geranylgeranyl 转移酶抑制剂-2147（GGTI-2147）也能在相当程度上抑制葡萄糖和氯化钾诱导的胰岛素分泌。用 3-vinylfarnesol 或 3-vinyl geranylgeraniol 处理 βTC3 细胞会导致未肾上腺素化的蛋白质在细胞膜部分积累。这些数据进一步支持了我们最初的观点，即抑制小分子量 G 蛋白的异戊烯化可能会阻碍它们与其可能的效应物之间的相互作用，而这可能是生理性胰岛素分泌所必需的。