(1R)-[1-2H]farnesyl diphosphate | 115826-59-0

• 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: (1R)-[1-2H]farnesyl diphosphate
• 英文别名: [(1R,2E,6E)-1-deuterio-3,7,11-trimethyldodeca-2,6,10-trienyl] phosphono hydrogen phosphate
• CAS: 115826-59-0；115826-60-3
• 化学式: C₁₅H₂₈O₇P₂
• 分子量: 383.323
• InChiKey: VWFJDQUYCIWHTN-WXQSZXNFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 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：
  7

反应信息

• 作为反应物：
  描述：

  (1R)-[1-2H]farnesyl diphosphate 在 recombinant Streptomyces avermitilis SAV_76 protein 作用下， 反应 12.0h， 生成 avermitilol
  参考文献：
  名称：

  Streptomyces avermitilis 的基因组挖掘：SAV_76 的克隆和表征

  摘要：

  由 Streptomyces avermtilis 的 sav76 基因编码的萜烯合酶在大肠杆菌中表达为 N 端-His(6)-标签蛋白，使用密码子优化的合成基因。在 Mg(2+) 存在下将重组蛋白 SAV_76 与二磷酸法呢酯 (1, FPP) 一起孵育得到一种新的倍半萜醇阿维醇 (2)，其结构和立体化学由 (1)H、 (13) C、COSY、HMQC、HMBC 和 NOESY NMR，以及少量的锗烯 A (3)、锗烯 B (4) 和绿萝 (5)。2 的绝对构型由相应的 (R)-和 (S)-Mosher 酯的 (1)H NMR 分析确定。稳态动力学参数是 k(cat) 0.040 + /-0.001 s(-1) 和 K(m) 1.06 + /-0.11 microM。[1,1-(2)H(2)]FPP (1a) 与重组阿维菌醇合酶的单独孵育，(1S)-[1-(2)H]-FPP (1b) 和

  DOI：

  10.1021/ja103087w
• 作为产物：
  描述：

  Farnesal 在 titanium(IV) isopropylate 、 (R)-1,1'-Bi-2-naphthol 、 四丁基磷酸氢铵 、 三氯乙腈 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 25.08h， 生成 (1R)-[1-2H]farnesyl diphosphate
  参考文献：
  名称：

  重组角鲨烯合酶。不存在 NADPH 时合成非头尾类异戊二烯

  摘要：

  角鲨烯合酶 (SQase) 催化甾醇生物合成中的两个连续反应。第一种是两分子法呢基二磷酸酯 (FPP) 缩合形成环丙基羰基中间体二磷酸前角鲨烯 (PSPP)。PSPP 随后转化为角鲨烯 (SQ) 涉及碳骨架的广泛重排和 NADPH 依赖性还原。在缺乏 NADPH 的缓冲液中用 FPP 孵育截短的可溶形式的重组酵母 SQase 得到 (1R,2R,3R)-PSPP。随着孵育的继续，SQase 催化 PSPP 随后转化为三萜混合物。两种主要产品，(Z)-脱氢角鲨烯 (DSQ) 和 (R)-12-羟基角鲨烯 (HSQ)，在角鲨烯中发现的 FPP 法呢基单元之间具有相同的 1'-1 键。另一个主要产品，(10S,13S)-10-羟基葡萄球菌烯 (HBO)，在法呢基单元之间具有 1'-3 键。还形成了少量的 (S)-HSQ 和 (10R,13S)-HBO。产生了少量的另外三种三萜、HSQ 和 HBO

  DOI：

  10.1021/ja020410i

文献信息

• Cyclization Mechanism of Amorpha-4,11-diene Synthase, a Key Enzyme in Artemisinin Biosynthesis
  作者：Soon-Hee Kim、Keon Heo、Yung-Jin Chang、Si-Hyung Park、Sang-Ki Rhee、Soo-Un Kim

  DOI：10.1021/np050356u

  日期：2006.5.1

  3-hydride shift or two successive 1,2-shifts, and one involving a germacrenyl carbocation, were proposed and tested by analyzing the fate of farnesyl diphosphate H-1 hydrogen atoms through (1)H and (2)H NMR spectroscopy. Migration of one deuterium atom of [1,1-(2)H(2)]farnesyl diphosphate to H-10 of amorpha-4,11-diene singled out the bisabolyl carbocation mechanism with a 1,3-hydride shift. Further

  通过 amorpha-4,11-二烯合酶 (ADS) 将法呢基二磷酸环化为 amorpha-4,11-二烯，启动青蒿素的生物合成，青蒿素是临床上重要的抗疟药物前体。提出了三种可能的闭环机制，其中两种涉及红没药基碳阳离子中间体，然后是 1,3-氢化物转移或两个连续的 1,2-转移，另一种涉及锗烯基碳阳离子，并通过分析法呢基二磷酸的命运进行测试H-1 氢原子通过 (1)H 和 (2)H NMR 光谱。[1,1-(2)H(2)] 法呢基二磷酸的一个氘原子迁移到 amorpha-4,11-二烯的 H-10 中，挑出了具有 1,3-氢化物转变的红没药基碳正离子机制。通过与 (1R)- 和 (1S)-[1-(2)H] 法呢基二磷酸的酶反应获得了进一步的确认。结果表明，1R 化合物的氘保持在 H-6，而 1S 化合物的氘迁移到 amorpha-4,11-二烯的 H-10。当反应在 (2)H(2)O 中进行时，观察到一种氘在环化过程中并入
• Lessons from 1,3-Hydride Shifts in Sesquiterpene Cyclizations
  作者：Jan Rinkel、Patrick Rabe、Paolina Garbeva、Jeroen S. Dickschat

  DOI：10.1002/anie.201608042

  日期：2016.10.17

  initial 1,10‐cyclisation‐1,3‐hydride shift cascades. Enzymes with products of known absolute configuration showed a coherent stereochemical course, except for (−)‐α‐amorphene synthase, for which the obtained results are better explained by an initial 1,6‐cyclisation. The link between the absolute configuration of the product and the stereochemical course of the 1,3‐hydride shifts enabled assignment of

  用7种细菌倍半萜环化酶将立体标记的前体转化，以研究其最初的1,10-环化-1,3-氢化物移位级联反应的立体化学。带有已知绝对构型的产物的酶显示出连贯的立体化学过程，除了（-）-α-Amorphene合酶外，最初的1,6-环化可以更好地解释所获得的结果。产品的绝对构型与1,3-氢化物转变的立体化学过程之间的联系使得可以分配三种酶产物的绝对构型，这可以通过常见副产物胚芽戊二烯D-4-ol的绝对构型独立确认。
• 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.
• Wang, Chieh-Mei; Hopson, Russell; Lin, Xin, Journal of the American Chemical Society, 2009, vol. 131, p. 8360 - 8361
  作者：Wang, Chieh-Mei、Hopson, Russell、Lin, Xin、Cane, David E.

  DOI：——

  日期：——
• Genome Mining in <i>Streptomyces </i><i>c</i><i>oelicolor</i>:  Molecular Cloning and Characterization of a New Sesquiterpene Synthase
  作者：Xin Lin、Russell Hopson、David E. Cane

  DOI：10.1021/ja061292s

  日期：2006.5.1

  The terpene synthase encoded by the SCO5222 (SC7E4.19) gene of Streptomyces coelicolor was cloned by PCR and expressed in Escherichia coli as an N-terminal-His6-tag protein. Incubation of the recombinant protein, SCO5222p, with farnesyl diphosphate (1, FPP) in the presence of Mg(II) gave a new sesquiterpene, (+)-epi-isozizaene (2), whose structure and stereochemistry were determined by a combination of 1H, 13C, COSY, HMQC, HMBC, and NOESY NMR. The steady-state kinetic parameters were kcat 0.049 +/- 0.001 s-1 and a Km (FPP) of 147 +/- 14 nM. Individual incubations of recombinant epi-isozizaene synthase with [1,1-2H2]FPP (1a), (1R)-[1-2H]-FPP (1b), and (1S)-[1-2H]-FPP (1c) and NMR analysis of the resulting deuterated epi-isozizaenes supported an isomerization-cyclization-rearrangement mechanism involving the intermediacy of (3R)-nerolidyl diphosphate (3).