10-fluorofarnesyl diphosphate | 161835-49-0

• 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: 10-fluorofarnesyl diphosphate
• 英文别名: [(2E,6E)-10-fluoro-3,7,11-trimethyldodeca-2,6,10-trienyl] phosphono hydrogen phosphate
• CAS: 161835-49-0
• 化学式: C₁₅H₂₇FO₇P₂
• 分子量: 400.321
• InChiKey: QVRGSZVZGWDKGW-BIVKKUJPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  10-fluorofarnesyl diphosphate 在 magnesium chloride 作用下， 以 正己烷 为溶剂， 反应 0.2h， 生成 10-fluorogermacrene A
  参考文献：
  名称：

  从现代 (+)-Germacrene A 合酶重建 α-Humulene 合酶的进化和机制见解

  摘要：

  来自加拿大一枝黄花的 Germacrene A 合酶 (GAS) 催化法呢基二磷酸 (FDP) 转化为植物倍半萜烯 (+)-germacrene A。二磷酸酯排出后，法呢基阳离子与远端 10,11-双键反应生成 Germacrene A ( >96%) 和 <2% α-葎草烯，这是由 FDP 的 1,11-环化产生的。通过1,10-和1,11-合酶的氨基酸序列比对以及X射线晶体结构与GAS同源模型的比较，研究了GAS 1,11-活性的起源；确定了可能导致 GAS 的主要 1,10-环化活性的三元组 [Thr 401-Gly 402-Gly 403]。用尺寸增加的残基替换 Gly 402 导致 1,11-环化逐渐增加。这些 1,10- /1 的催化稳定性，11-GAS 变体指出 Gly 402 是具有进化意义的功能转换，并表明具有严格功能的酶是通过少量替换从不太特定的祖先进化而来的。在替换同源活性位点残基

  DOI：

  10.1021/ja5066366

文献信息

• Chemoenzymatic preparation of germacrene analogues
  作者：Oscar Cascón、Sabrina Touchet、David J. Miller、Veronica Gonzalez、Juan A. Faraldos、Rudolf K. Allemann

  DOI：10.1039/c2cc35542f

  日期：——

  A small library of novel germacrenes was generated using a combination of two plant enzymes, germacrene A synthase, and D synthase and modified farnesyl diphosphate (FDP) analogues. This chemoenzymatic approach allows the preparation of potentially valuable volatiles for biological studies.

  利用两种植物酶--胚芽烯 A 合酶和胚芽烯 D 合酶--以及改良的二磷酸法呢基类似物，生成了一个小型的新型胚芽烯类化合物库。这种化学酶法可以制备出具有潜在价值的挥发性物质，用于生物研究。
• A 1,6-Ring Closure Mechanism for (+)-δ-Cadinene Synthase?
  作者：Juan A. Faraldos、David J. Miller、Verónica González、Zulfa Yoosuf-Aly、Oscar Cascón、Amang Li、Rudolf K. Allemann

  DOI：10.1021/ja211820p

  日期：2012.4.4

  Recombinant (+)-delta-cadinene synthase (DCS) from Gossypium arboreum catalyzes the metal-dependent cyclization of (E,E)-farnesyl diphosphate (FDP) to the cadinane sesquiterpene delta-cadinene, the parent hydrocarbon of cotton phytoalexins such as gossypol. In contrast to some other sesquiterpene cyclases, DCS carries out this transformation with >98% fidelity but, as a consequence, leaves no mechanistic traces of its mode of action. The formation of (+)-delta-cadinene has been shown to occur via the enzyme-bound intermediate (3R)-nerolidyl diphosphate (NDP), which in turn has been postulated to be converted to cis-germacradienyl cation after a 1,10-cyclization. A subsequent 1,3-hydride shift would then relocate the carbocation within the transient macrocycle to expedite a second cyclization that yields the cadinenyl cation with the correct cis stereochemistry found in (+)-delta-cadinene. An elegant 1,10-mechanistic pathway that avoids the formation of (3R)-NDP has also been suggested. In this alternative scenario, the final cadinenyl cation is proposed to be formed through the intermediacy of trans, trans-germacradienyl cation and germacrene D. In addition, an alternative 1,6-ring closure mechanism via the bisabolyl cation has previously been envisioned. We report here a detailed investigation of the catalytic mechanism of DCS using a variety of mechanistic probes including, among others, deuterated and fluorinated FDPs. Farnesyl diphosphate analogues with fluorine at C2 and C10 acted as inhibitors of DCS, but intriguingly, after prolonged overnight incubations, they yielded 2F-germacrene(s) and a 10F-humulene, respectively. The observed 1,10-, and to a lesser extent, 1,11-cyclization activity of DCS with these fluorinated substrates is consistent with the postulated macrocyclization mechanism(s) en route to (+)-delta-cadinene. On the other hand, mechanistic results from incubations of DCS with 6F-FPP, (2Z,6E)-FDP, neryl diphosphate, 6,7-dihydro-FDP, and NDP seem to be in better agreement with the potential involvement of the alternative biosynthetic 1,6-ring closure pathway. In particular, the strong inhibition of DCS by 6F-FDP, coupled to the exclusive bisabolyl- and terpinyl-derived product profiles observed for the DCS-catalyzed turnover of (2Z,6E)-farnesyl and neryl diphosphates, suggested the intermediacy of alpha-bisabolyl cation. DCS incubations with enantiomerically pure [1-H-2(1)](1R)-FDP revealed that the putative bisabolyl-derived 1,6-pathway proceeds through (3R)-nerolidyl diphosphate (NDP), is consistent with previous deuterium-labeling studies, and accounts for the cis stereochemistry characteristic of cadinenyl-derived sesquiterpenes. While the results reported here do not unambiguously rule in favor of 1,6- or 1,10-cyclization, they demonstrate the mechanistic versatility inherent to DCS and highlight the possible existence of multiple mechanistic pathways.