10-fluoro-α-humulene | 1366590-86-4

• 分子结构分类: 有机化合物 - 碳氢化合物 - 不饱和烃
• 英文名称: 10-fluoro-α-humulene
• CAS: 1366590-86-4
• 化学式: C₁₅H₂₃F
• 分子量: 222.346
• InChiKey: ILVFVVDEUPFYJF-AHQYSDGPSA-N

反应信息

• 作为产物：
  描述：

  10-fluorofarnesyl diphosphate 在 (R)-germacrene A synthase 、 3-[(3-cholamidopropyl)dimethylammonio]propanesulfonate 、 三羟甲基氨基甲烷 、 2-巯基乙醇 、 magnesium chloride 作用下， 以 氘代氯仿 、 水 为溶剂， 反应 24.0h， 生成 10-fluoro-α-humulene
  参考文献：
  名称：

  Chemoenzymatic preparation of germacrene analogues

  摘要：

  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。

  DOI：

  10.1039/c2cc35542f

文献信息

• 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.