(+)-ent-3β-hydroxyisopimara-8(14),15-diene | 30294-96-3

• 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: (+)-ent-3β-hydroxyisopimara-8(14),15-diene
• 英文别名: Ent-sandaracopimaradien-3beta-ol；(2R,4aS,4bR,7S,10aS)-7-ethenyl-1,1,4a,7-tetramethyl-3,4,4b,5,6,9,10,10a-octahydro-2H-phenanthren-2-ol
• CAS: 30294-96-3
• 化学式: C₂₀H₃₂O
• 分子量: 288.473
• InChiKey: ATQOOBSXQVRQPY-GNVJSZRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.8
• 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：

  (+)-ent-3β-hydroxyisopimara-8(14),15-diene 在 selenium(IV) oxide 、 AcO₂ 、 水 、 二甲基亚砜 作用下， 以 吡啶 、 溶剂黄146 、 苯 为溶剂， 反应 0.03h， 生成 Acetic acid (2R,4aR,4bS,7S,10aS)-1,1,4a,7-tetramethyl-9-oxo-7-vinyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydro-phenanthren-2-yl ester
  参考文献：
  名称：

  Synthesis of oryzalexins a, b and c, the diterpenoidal phytoalexins isolated from rice blast leaves infected with pyricularia oryzae

  摘要：

  DOI：

  10.1016/s0040-4020(01)91369-9
• 作为产物：
  描述：

  tert-Butyl-dimethyl-((2S,4aR,4bS,10aR)-1,1,4a,7-tetramethyl-7-vinyl-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydro-phenanthren-2-yloxy)-silane 在 盐酸 、 氢氟酸 、 对甲苯磺酸 作用下， 以 甲醇 、 乙腈 、 苯 为溶剂， 反应 2.75h， 生成 (+)-ent-3β-hydroxyisopimara-8(14),15-diene
  参考文献：
  名称：

  Synthesis of oryzalexins a, b and c, the diterpenoidal phytoalexins isolated from rice blast leaves infected with pyricularia oryzae

  摘要：

  DOI：

  10.1016/s0040-4020(01)91369-9

文献信息

• CYP701A8: A Rice <i>ent</i>-Kaurene Oxidase Paralog Diverted to More Specialized Diterpenoid Metabolism    
  作者：Qiang Wang、Matthew L. Hillwig、Yisheng Wu、Reuben J. Peters

  DOI：10.1104/pp.111.187518

  日期：2012.3.6

  All higher plants contain an ent-kaurene oxidase (KO), as such a cytochrome P450 (CYP) 701 family member is required for gibberellin (GA) phytohormone biosynthesis. While gene expansion and functional diversification of GA-biosynthesis-derived diterpene synthases into more specialized metabolism has been demonstrated, no functionally divergent KO/CYP701 homologs have been previously identified. Rice (Oryza sativa) contains five CYP701A subfamily members in its genome, despite the fact that only one (OsKO2/CYP701A6) is required for GA biosynthesis. Here we demonstrate that one of the other rice CYP701A subfamily members, OsKOL4/CYP701A8, does not catalyze the prototypical conversion of the ent-kaurene C4α-methyl to a carboxylic acid, but instead carries out hydroxylation at the nearby C3α position in a number of related diterpenes. In particular, under conditions where OsKO2 catalyzes the expected conversion of ent-kaurene to ent-kaurenoic acid required for GA biosynthesis, OsKOL4 instead efficiently reacts with ent-sandaracopimaradiene and ent-cassadiene to produce the corresponding C3α-hydroxylated diterpenoids. These compounds are expected intermediates in biosynthesis of the oryzalexin and phytocassane families of rice antifungal phytoalexins, respectively, and can be detected in rice plants under the appropriate conditions. Thus, it appears that OsKOL4 plays a role in the more specialized diterpenoid metabolism of rice, and our results provide evidence for divergence of a KO/CYP701 family member from GA biosynthesis. This further expands the range of enzymes recruited from the ancestral GA primary pathway to the more complex and specialized labdane-related diterpenoid metabolic network found in rice.

  所有高等植物都含有一种ent-kaurene氧化酶（KO），因此需要一个细胞色素P450（CYP）701家族成员来进行赤霉素（GA）植物激素的生物合成。虽然GA生物合成衍生的二萜合成酶的基因扩张和功能多样化已经得到证明，但以前尚未发现功能分化的KO/CYP701同源物。水稻（Oryza sativa）的基因组中包含五个CYP701A亚家族成员，尽管仅有一个（OsKO2/CYP701A6）用于GA生物合成。在这里，我们证明了其他水稻CYP701A亚家族成员之一，OsKOL4/CYP701A8，不会催化ent-kaurene C4α-甲基的原型转化为羧酸，而是在许多相关二萜中在附近的C3α位置进行羟化。特别是，在OsKO2催化ent-kaurene转化为GA生物合成所需的ent-kaurenoic酸的预期转化的条件下，OsKOL4则有效地与ent-sandaracopimaradiene和ent-cassadiene反应，产生相应的C3α-羟基化二萜。这些化合物预计是水稻抗真菌植物次生代谢物oryzalexin和phytocassane家族的生物合成中间体，可以在适当条件下检测到水稻植物中。因此，看来OsKOL4在水稻更为专业的二萜代谢中扮演着一种角色，我们的结果提供了KO/CYP701家族成员从GA生物合成中分化的证据。这进一步扩大了从祖先GA主要途径中招募的酶范围，以适应水稻中发现的更复杂和专业的labdane相关二萜代谢网络。

• Characterization of CYP76M5–8 Indicates Metabolic Plasticity within a Plant Biosynthetic Gene Cluster
  作者：Qiang Wang、Matthew L. Hillwig、Kazunori Okada、Kohei Yamazaki、Yisheng Wu、Sivakumar Swaminathan、Hisakazu Yamane、Reuben J. Peters

  DOI：10.1074/jbc.m111.305599

  日期：2012.2

  Intriguingly, the preceding diterpene synthase for oryzalexin biosynthesis, unlike that for the phytocassanes, is not found in the chromosome 2 diterpenoid biosynthetic gene cluster. Accordingly, our results not only uncover a complex evolutionary history, but also further suggest some intriguing differences between plant biosynthetic gene clusters and the seemingly similar microbial operons. The implications

  最近的报告揭示了植物专门/次级代谢中特定生物合成途径的酶基因的基因组聚类。水稻（Oryza sativa）携带两个这样的簇用于生产抗菌二萜类植物抗毒素，2 号染色体上的簇包含细胞色素 P450 CYP76M 亚家族（CYP76M5-8）的四个密切相关/同源成员。值得注意的是，这些 CYP 的潜在进化扩展似乎发生在祖先生物合成基因簇组装之后，表明它们具有不同的作用。已经证明 CYP76M7 催化 ent-cassadiene 的 C11α-羟基化，并可能介导衍生的植物卡桑类植物抗毒素生物合成的早期步骤。在这里，我们报告了 CYP76M5、-6 和 -8 的生化特征。我们的结果表明 CYP76M8 是一种多功能/混杂的羟化酶，与 CYP76M8 相比，CYP76M5 和 -7 似乎仅提供多余的活性，而 CYP76M6 似乎提供多余的和新的活性。RNAi 介导的 CYP76M7 和 -8 双重敲
• Picking sides: distinct roles for CYP76M6 and CYP76M8 in rice oryzalexin biosynthesis
  作者：Yisheng Wu、Qiang Wang、Matthew L. Hillwig、Reuben J. Peters

  DOI：10.1042/bj20130574

  日期：2013.9.1

  Natural products biosynthesis often requires the action of multiple CYPs (cytochromes P450), whose ability to introduce oxygen, increasing solubility, is critical for imparting biological activity. In previous investigations of rice diterpenoid biosynthesis, we characterized CYPs that catalyse alternative hydroxylation of ent-sandaracopimaradiene, the precursor to the rice oryzalexin antibiotic phytoalexins. In particular, CYP76M5, CYP76M6 and CYP76M8 were all shown to carry out C-7β hydroxylation, whereas CYP701A8 catalyses C-3α hydroxylation, with oxy groups found at both positions in oryzalexins A–D, suggesting that these may act consecutively in oryzalexin biosynthesis. In the present paper, we report that, although CYP701A8 only poorly reacts with 7β-hydroxy-ent-sandaracopimaradiene, CYP76M6 and CYP76M8 readily react with 3α-hydroxy-ent-sandaracopimaradiene. Notably, their activity yields distinct products, resulting from hydroxylation at C-9β by CYP76M6 or C-7β by CYP76M8, on different sides of the core tricyclic ring structure. Thus CYP76M6 and CYP76M8 have distinct non-redundant roles in orzyalexin biosynthesis. Moreover, the resulting 3α,7β- and 3α,9β-diols correspond to oryzalexins D and E respectively. Accordingly, the results of the present study complete the functional identification of the biosynthetic pathway underlying the production of these bioactive phytoalexins. In addition, the altered regiochemistry catalysed by CYP76M6 following C-3α hydroxylation has some implications for its active-site configuration, offering further molecular insight.

  天然产物的生物合成通常需要多种 CYPs（细胞色素 P450）的作用，它们引入氧气、增加溶解度的能力对于赋予生物活性至关重要。在以前对水稻二萜生物合成的研究中，我们对催化ent-sandaracopimaradiene（水稻oryzalexin抗生素植物雌激素的前体）替代羟基化的 CYPs 进行了鉴定。其中，CYP76M5、CYP76M6 和 CYP76M8 都被证明能进行 C-7β 羟基化，而 CYP701A8 则催化 C-3α 羟基化，在 oryzalexins A-D 的两个位置上都发现了氧基，这表明它们可能在 oryzalexin 的生物合成中连续发挥作用。在本文中，我们报告了尽管 CYP701A8 与 7β-hydroxy-ent-sandaracopimaradiene 的反应很弱，但 CYP76M6 和 CYP76M8 却很容易与 3α-hydroxy-ent-sandaracopimaradiene 发生反应。值得注意的是，CYP76M6 和 CYP76M8 在三环核心结构的不同侧 C-9β 或 C-7β 处进行羟基化反应会产生不同的产物。因此，CYP76M6 和 CYP76M8 在橙皮苷的生物合成过程中具有不同的非冗余作用。此外，由此产生的 3α,7β- 和 3α,9β-二醇分别对应于奥氮杂环辛 D 和 E。因此，本研究的结果完成了这些具有生物活性的植物毒素的生物合成途径的功能鉴定。此外，CYP76M6 在 C-3α 羟基化后催化的改变的区域化学对其活性位点构型有一定的影响，从而提供了进一步的分子见解。
• Synthesis of oryzalexins a, b and c, the diterpenoidal phytoalexins isolated from rice blast leaves infected with pyricularia oryzae
  作者：Kenji Mori、Michiru Waku

  DOI：10.1016/s0040-4020(01)91369-9

  日期：1985.1