(2-cis,6-trans)-farnesyl diphosphate | 40716-68-5

• 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: (2-cis,6-trans)-farnesyl diphosphate
• 英文别名: (2Z,6E)-farnesyl diphosphate；(Z,E)-farnesyl diphosphate；Z,E-farnesyl pyrophosphate；(2Z)-farnesyl diphosphate；Z,E-farnesyl diphosphate；farnesyl diphosphate；2-cis,6-trans-Farnesyl diphosphate；phosphono [(2Z,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl] hydrogen phosphate
• CAS: 40716-68-5
• 化学式: C₁₅H₂₈O₇P₂
• 分子量: 382.331
• InChiKey: VWFJDQUYCIWHTN-PVMFERMNSA-N

物化性质

• 沸点：
  533.8±60.0 °C(Predicted)
• 密度：
  1.233±0.06 g/cm3(Predicted)

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：

  (2-cis,6-trans)-farnesyl diphosphate 在 calf intestinal phosphatase 、 水 作用下， 反应 1.0h， 生成 (2Z,6E)-3,7,11-三甲基十二碳-2,6,10-三烯-1-醇
  参考文献：
  名称：

  通过定点诱变和形态发生研究三齿蒿法呢基二磷酸合酶和菊基二磷酸合酶的结构-功能

  摘要：

  来自 Artemisia tridentata ssp 的法呢基二磷酸合酶 (FPPase) 和菊基二磷酸合酶 (CPPase) 的氨基酸序列。Spiciformis，减去它们的叶绿体靶向区域，71% 相同，90% 相似。FPPase 通过将异戊烯基二磷酸 (IPP) 与二甲基烯丙基二磷酸 (DMAPP) 偶联，然后再与香叶基二磷酸 (GPP) 偶联，有效且选择性地合成“常规”倍半萜类法呢基二磷酸 (FPP)。相比之下，CPPase 是一种低效的混杂酶，它从两个分子的 DMAPP 中合成“不规则”单萜菊酯二磷酸 (CPP)、薰衣草二磷酸 (LPP) 和微量的马可二磷酸 (MPP)，并将 IPP 与 DMAPP 偶联以形成给 GPP。A. tridentata FPPase 和 CPPase 属于链延长蛋白家族 (PF00348)，萜类合酶超家族 (CL0613) 的一个亚群，其成员具有特征性

  DOI：

  10.1021/jacs.7b07608
• 作为产物：
  描述：

  (2Z,6E)-3,7,11-三甲基十二碳-2,6,10-三烯-1-醇 在 草酰氯 、 tris(tetra-n-butylammonium) hydrogen pyrophosphate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 1.5h， 生成 (2-cis,6-trans)-farnesyl diphosphate
  参考文献：
  名称：

  Incorporation of Farnesyl Pyrophosphate Derivertives into Abscisic Acid and Its Biosynthetic Intermediates in Cevcospova cruenta

  摘要：

  为了研究脱落酸产生真菌 Cercospora cruenta 从(2E,6E)-法呢基焦磷酸盐到(2Z,4E)-γ-亚氨基乙醇的转化过程，我们制备并饲喂了[2-14C]-C15中间产物。(2E,6E)-法呢酰焦磷酸、(2Z,4E)-γ-亚氨基乙醇及其焦磷酸等底物被并入 ABA 及其已知的生物合成前体。研究表明，(2E,6E>法呢醇焦磷酸酯是通过脱氢、异构化、环化和水解四个连续步骤转化为(2Z,4E)-γ-亚氨基乙醇的。

  DOI：

  10.1271/bbb.61.821

文献信息

• Stereospecific Synthesis and Biological Evaluation of Farnesyl Diphosphate Isomers
  作者：Ying Shao、Jeffrey T. Eummer、Richard A. Gibbs

  DOI：10.1021/ol990714i

  日期：1999.8.1

  unified, stereospecific synthetic route to the three geometric isomers of (E,E)-farnesyl diphosphate (E,E-FPP) (1, 2, and 3) has been developed. The key feature of this synthesis is the ability to control the stereochemistry of triflation of the beta-ketoester 10 to give either 11 or 14. Preliminary evaluation of these compounds with protein-farnesyl transferase indicates that 1 and 2 are surprisingly

  [公式：见正文]已开发出统一的立体定向合成路线，可合成（E，E）-法呢基二磷酸酯（E，E-FPP）（1、2和3）的三个几何异构体。该合成的关键特征是能够控制β-酮酸酯10的三氟甲基化的立体化学，从而得到11或14。用蛋白-法呢基转移酶对这些化合物进行的初步评估表明，1和2是令人惊讶的有效底物；而2和3是有效的底物。但是，Z，Z-FPP（3）是较差的底物和亚微摩尔抑制剂。
• Farnesyl Diphosphate Synthase:  The Art of Compromise between Substrate Selectivity and Stereoselectivity
  作者：Hirekodathakallu V. Thulasiram、C. Dale Poulter

  DOI：10.1021/ja065573b

  日期：2006.12.1

  synthesized in vivo by E. coli FPP synthase. When (R)-[2-2H]IPP was a substrate for chain elongation, no deuterium was found in the chain elongation products. In contrast, the deuterium in (S)-[2-2H]IPP was incorporated into all of the products. Thus, the pro-R hydrogen at C2 of IPP is lost when the E- and Z-double bond isomers are formed. The synthesis of Z-double bond isomers by FPP synthase during

  法呢基二磷酸 (FPP) 合酶催化异戊烯二磷酸 (IPP, C5) 与二甲基烯丙基二磷酸 (DMAPP, C5) 和香叶基二磷酸 (GPP, C10) 的连续头尾缩合得到 (E, E)-FPP (C15 ）。该酶属于基因上不同的链延长酶家族，在每次添加五碳异戊二烯单元期间安装 E-双键。对来自禽 FPP 合酶的 C10 和 C15 产物的分析表明，在 C5 --> C10 和 C10 过程中，与 E 异构体一起形成了少量的二磷酸橙花酯 (Z-C10) 和 (Z,E)-FPP --> C15 反应。对于来自大肠杆菌、三齿蒿（鼠尾草）、激烈火球菌和自养甲烷杆菌的 FPP 合酶以及由大肠杆菌 FPP 合酶在体内合成的 GPP 和 FPP 获得了类似的结果。当 (R)-[2-2H]IPP 是链伸长的底物时，在链伸长产物中没有发现氘。相比之下，(S)-[2-2H]IPP 中的氘被掺入到所有产品中。因此，当形成
• Insights into the Mechanism of the Antibiotic-Synthesizing Enzyme MoeO5 from Crystal Structures of Different Complexes
  作者：Feifei Ren、Tzu-Ping Ko、Xinxin Feng、Chun-Hsiang Huang、Hsiu-Chien Chan、Yumei Hu、Ke Wang、Yanhe Ma、Po-Huang Liang、Andrew H.-J. Wang、Eric Oldfield、Rey-Ting Guo

  DOI：10.1002/anie.201108002

  日期：2012.4.23

  Barrel‐shaped: The enzyme MoeO5 catalyzes the transfer of the C15 moiety of farnesyl pyrophosphate to the 2‐hydroxy group of 3‐phosphoglycerate to give 2‐(Z,E)‐farnesyl‐3‐phosphoglycerate (FPG; ligand in the center of the shown structure). X‐ray crystallographic structures showed that MoeO5 forms a triose‐phosphate‐isomerase barrel structure and binds FPG in a curved pocket, mainly as a result of its

  桶形：酶 MoeO5 催化法呢基焦磷酸的 C 15部分转移到 3-磷酸甘油酸的 2-羟基，得到 2-( Z , E )-法呢基-3-磷酸甘油酸酯（FPG；中心配体）所示结构）。X 射线晶体结构表明，MoeO5 形成丙糖-磷酸-异构酶桶状结构，并在弯曲的口袋中结合 FPG，主要是由于其长 λ3 环（图片中的洋红色）。
• Alternate Cyclization Cascade Initiated by Substrate Isomer in Multiproduct Terpene Synthase from <i>Medicago truncatula</i>
  作者：Abith Vattekkatte、Stefan Garms、Wilhelm Boland

  DOI：10.1021/acs.joc.6b02696

  日期：2017.3.17

  isolated from Medicago truncatula generates 27 optically pure products from its natural substrate (2E,6E)-farnesyl diphosphate (FDP). In order to study the promiscuity of MtTPS5, (2Z,6E)-FDP, an analogue of presumptive reaction intermediates from natural reaction cascade, was utilized as a substrate. This stereoisomer induced a novel cyclization pathway leading to sesquiterpenes based on humulane, amorphene

  萜烯合酶的滥交导致自然界中发现的萜烯种类繁多。从梅花苜蓿中分离的多产物倍半萜烯合酶MtTPS5从其天然底物（2 E，6 E）-法呢基二磷酸酯（FDP）产生27种光学纯产物。为了研究MtTPS5的滥交，（2 Ž，6 ë）- FDP，从自然反应级联推定反应中间体的类似物，被用作基底。该立体异构体诱导了一种新的环化途径，从而导致了基于胡mul烷，紫穗槐和喜马al烷骨架的倍半萜。有趣的是，这些产品均未与将MtTPS5与天然（2E，6 E）-FDP。进一步确定每种产物的绝对构型有助于重建反应级联的立体化学路线。有趣的是，观察到每种产物仅存在一种对映异构体，表明酶促反应具有高度立体特异性。萜烯合酶的底物混杂性使生物能够利用现有酶获得高光学纯度的新型化学束。这些替代产品在天然草食动物诱发的run藜挥发物中的存在表明了这种机制的存在。
• 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.