preaustinoid A1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: preaustinoid A1
• 英文别名: methyl (1R,2S,5S,11S,12S,14R,16S)-16-hydroxy-2,6,6,11,14,16-hexamethyl-18-methylidene-8,15,17-trioxo-7-oxatetracyclo[12.3.1.02,12.05,11]octadecane-1-carboxylate
• 化学式: C₂₆H₃₆O₇
• 分子量: 460.568
• InChiKey: XBLDTXYFLHSWHN-RFMSQVAGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  33
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  preaustinoid A1 在 α-ketoglutarate-dependent dioxygenase PrhA 作用下， 以5.84 mg的产率得到berkeleyone B
  参考文献：
  名称：

  Discovery of Key Dioxygenases that Diverged the Paraherquonin and Acetoxydehydroaustin Pathways in Penicillium brasilianum

  摘要：

  Paraherquonin (1), a fungal meroterpenoid produced by Penicillium brasilianum NBRC 6234, possesses a unique, highly congested hexacyclic molecular architecture. Here we identified the biosynthetic gene cluster of 1 (the prh cluster) and elucidated the pathway up to berkeleydione (2), which serves as the key intermediate for the biosynthesis of I as well as many other meroterpenoids. Interestingly, the nonheme iron and a-ketoglutarate-dependent dioxygenase PrhA constructs the cycloheptadiene moiety to afford 2 from preaustinoid A1 (6), probably via the homoallyl-homoallyl radical rearrangement. Additionally, another fungal strain, P. brasilianum MG11, which produces acetoxydehydroaustin instead of 1, was found to have a gene cluster nearly identical to the prh cluster. The dioxygenase encoded by the cluster shares 92% sequence identity with PrhA, and also accepts 6 but produces preaustinoid A3 (17) with a spiro-lactone system, generating a diverging point for the two different meroterpenoid pathways in the same species.

  DOI：

  10.1021/jacs.6b08424
• 作为产物：
  描述：

  3,7,11-三甲基-2,6,10-十二烷三烯-1-醇乙酸酯 在 吡啶 、 咪唑 、 2,6-二甲基吡啶 、 2,4,6-三甲基吡啶 、 4-二甲氨基吡啶 、 二氯二茂钛 、 potassium osmate(VI) dihydrate 、 锰 、 正丁基锂 、 三甲基氯硅烷 、 甲基磺酰胺 、 氯化二乙基铝 、 C₆₅H₈₃N₆O₄⁽¹⁺⁾*I^(1-) 、 碳酸氢钠 、 potassium carbonate 、 戴斯-马丁氧化剂 、 对甲苯磺酸 、 甲基磺酰氯 、 三乙胺 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 lithium chloride 、 lithium hexamethyldisilazane 、 potassium hexacyanoferrate(III) 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 、 叔丁醇 为溶剂， 反应 143.41h， 生成 preaustinoid A1
  参考文献：
  名称：

  Berkeleyone A 和 Preaustinoids 的对映选择性全合成

  摘要：

  在此，我们报告了 3,5-二甲基橙霉酸衍生的类萜 (-)-伯克利酮 A 及其五种同源物 ((-)-preaustinoids A、A1、B、B1 和 B2) 在 12-15 个步骤中的首次对映选择性全合成，从市售的 2,4,6-三羟基苯甲酸水合物开始。基于对 D 环内潜在对称性的认识，我们的聚合合成具有两个关键反应：1）对称破坏、非对映选择性脱芳烃烷基化以组装整个碳核，以及 2）Sc(OTf) 3介导的顺序 Krapcho脱烷氧基羰基化/羰基α-叔-烷基化形成复杂的双环[3.3.1]壬烷骨架。我们还进行了初步仿生研究，并发现了一系列重排（α-酮醇、α-羟基-β-二酮等），这些重排负责将 (-)-berkeleyone A 仿生多样化为其五个前类同系物。

  DOI：

  10.1002/anie.202104014

文献信息

• Structure function and engineering of multifunctional non-heme iron dependent oxygenases in fungal meroterpenoid biosynthesis
  作者：Yu Nakashima、Takahiro Mori、Hitomi Nakamura、Takayoshi Awakawa、Shotaro Hoshino、Miki Senda、Toshiya Senda、Ikuro Abe

  DOI：10.1038/s41467-017-02371-w

  日期：——

  versatile family of enzymes is to understand their structure-function relationship. AusE from Aspergillus nidulans and PrhA from Penicillium brasilianum are two highly homologous Fe(II)/αKG oxygenases in fungal meroterpenoid biosynthetic pathways that use preaustinoid A1 as a common substrate to catalyze divergent rearrangement reactions to form the spiro-lactone in austinol and cycloheptadiene moiety

  非血红素铁和α-酮戊二酸（αKG）氧化酶使用单个亚铁离子辅因子催化显着不同的反应。研究这种多用途酶家族的主要挑战是了解它们的结构-功能关系。来自构巢曲霉的AusE和来自巴西青霉的PrhA是真菌类金属萜类生物合成途径中的两种高度同源的Fe（II）/αKG加氧酶，它们使用类前弹性蛋白A1作为常见底物来催化不同的重排反应，从而在奥斯丁醇和环庚二烯中形成螺内酯部分分别为副herquonin。在此，我们报告了AusE和PrhA的比较结构研究，该研究导致确定了控制其反应性的三个关键活性位点残基。这些残基的结构导向诱变导致AusE和PrhA功能成功相互转化，以及产生具有扩大的催化功能的PrhA双和三重突变体。因此，多功能Fe（II）/αKG加氧酶的操作为生物催化剂的未来发展提供了一个极好的平台。
• Spiro-Ring Formation is Catalyzed by a Multifunctional Dioxygenase in Austinol Biosynthesis
  作者：Yudai Matsuda、Takayoshi Awakawa、Toshiyuki Wakimoto、Ikuro Abe

  DOI：10.1021/ja405518u

  日期：2013.7.31

  Austinol, a fungal meroterpenoid derived from 3,5-dimethylorsellinic acid, has a unique chemical structure with a remarkable spiro-lactone ring system. Despite the recent identification of its biosynthetic gene cluster and targeted gene-deletion experiments, the process for the conversion of protoaustinoid A (2), the first tetracyclic biosynthetic intermediate, to the spirolactone preaustinoid A3 (7) has remained enigmatic. Here we report the mechanistic details of the enzyme-catalyzed, stereospecific spiro-lactone ring-forming reaction, which is catalyzed by a non-heme iron-dependent dioxygenase, AusE, along with two flavin monooxygenases, the 5'-hydroxylase AusB and the Baeyer-Villiger monooxygenase AusC. Remarkably, AusE is a multifunctional dioxygenase that is responsible for the iterative oxidation steps, including the oxidative spiro-ring-forming reaction, to produce the austinol scaffold.
• Enantioselective Total Synthesis of Berkeleyone A and Preaustinoids
  作者：Yang Zhang、Yunpeng Ji、Ivan Franzoni、Chuning Guo、Hongli Jia、Benke Hong、Houhua Li

  DOI：10.1002/anie.202104014

  日期：2021.6.25

  enantioselective total synthesis of 3,5-dimethylorsellinic acid-derived meroterpenoids (−)-berkeleyone A and its five congeners ((−)-preaustinoids A, A1, B, B1, and B2) in 12–15 steps, starting from commercially available 2,4,6-trihydroxybenzoic acid hydrate. Based upon the recognition of latent symmetry within D-ring, our convergent synthesis features two critical reactions: 1) a symmetry-breaking, diastereoselective

  在此，我们报告了 3,5-二甲基橙霉酸衍生的类萜 (-)-伯克利酮 A 及其五种同源物 ((-)-preaustinoids A、A1、B、B1 和 B2) 在 12-15 个步骤中的首次对映选择性全合成，从市售的 2,4,6-三羟基苯甲酸水合物开始。基于对 D 环内潜在对称性的认识，我们的聚合合成具有两个关键反应：1）对称破坏、非对映选择性脱芳烃烷基化以组装整个碳核，以及 2）Sc(OTf) 3介导的顺序 Krapcho脱烷氧基羰基化/羰基α-叔-烷基化形成复杂的双环[3.3.1]壬烷骨架。我们还进行了初步仿生研究，并发现了一系列重排（α-酮醇、α-羟基-β-二酮等），这些重排负责将 (-)-berkeleyone A 仿生多样化为其五个前类同系物。
• Discovery of Key Dioxygenases that Diverged the Paraherquonin and Acetoxydehydroaustin Pathways in <i>Penicillium brasilianum</i>
  作者：Yudai Matsuda、Taiki Iwabuchi、Takayuki Fujimoto、Takayoshi Awakawa、Yu Nakashima、Takahiro Mori、Huiping Zhang、Fumiaki Hayashi、Ikuro Abe

  DOI：10.1021/jacs.6b08424

  日期：2016.9.28

  Paraherquonin (1), a fungal meroterpenoid produced by Penicillium brasilianum NBRC 6234, possesses a unique, highly congested hexacyclic molecular architecture. Here we identified the biosynthetic gene cluster of 1 (the prh cluster) and elucidated the pathway up to berkeleydione (2), which serves as the key intermediate for the biosynthesis of I as well as many other meroterpenoids. Interestingly, the nonheme iron and a-ketoglutarate-dependent dioxygenase PrhA constructs the cycloheptadiene moiety to afford 2 from preaustinoid A1 (6), probably via the homoallyl-homoallyl radical rearrangement. Additionally, another fungal strain, P. brasilianum MG11, which produces acetoxydehydroaustin instead of 1, was found to have a gene cluster nearly identical to the prh cluster. The dioxygenase encoded by the cluster shares 92% sequence identity with PrhA, and also accepts 6 but produces preaustinoid A3 (17) with a spiro-lactone system, generating a diverging point for the two different meroterpenoid pathways in the same species.