hexaacetoxy-2α,5α,7β,9α,10β,13α taxadiene-4(20),11 | 27854-04-2

• 英文名称: hexaacetoxy-2α,5α,7β,9α,10β,13α taxadiene-4(20),11
• 英文别名: taxa-4(20),11-dien-2α,5α,7β,9α,10β,13α-hexaacetate；2α,5α,7β,9α,10β,13α-hexaacetoxytaxa-4(20),11-diene；taxa-4(20),11-diene-2α,5α,7β,9α,10β,13α-hexanol hexaacetate；2α,5α,7β,9α,10β,13α-hexaacetoxy-4(20),11-taxadiene；Taxa-4(20),11-dien-2α,5α,7β,9α,10β,13α-hexaol-hexaacetat；2α,5α,7β,9α,10β,13α-hexaacetoxytaxa-5(20),11(12)-diene；taxa-4(20),11-diene-2a,5a,7b,9a,10b,13a-hexaol hexaacetate；taxadiene hexaacetate；[(1R,2R,3R,5S,7S,8S,9R,10R,13S)-2,5,7,9,10-pentaacetyloxy-8,12,15,15-tetramethyl-4-methylidene-13-tricyclo[9.3.1.03,8]pentadec-11-enyl] acetate
• CAS: 27854-04-2
• 化学式: C₃₂H₄₄O₁₂
• 分子量: 620.694
• InChiKey: VOUULHDFPJAWEH-KYYDYRBASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  44
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  158
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  hexaacetoxy-2α,5α,7β,9α,10β,13α taxadiene-4(20),11 在 甲醇 、 sodium methylate 、 cytochrome P₄₅₀ enzyme from Taxus-media oxetane synthase 作用下， 反应 27.0h， 生成 (1R,2R,3R,4S,7R,9S,10S,11R,12R,15S)-10,14,17,17-tetramethyl-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-ene-2,4,9,11,12,15-hexol
  参考文献：
  名称：

  A Cytochrome P450 Enzyme Catalyses Oxetane Ring Formation in Paclitaxel Biosynthesis

  摘要：

  Oxetane synthase (TmCYP1), a novel cytochrome P450 enzyme from Taxus×media cell cultures, has been functionally characterized to efficiently catalyse the formation of the oxetane ring in tetracyclic taxoids. Transient expression of TmCYP1 in Nicotiana benthamiana using 2α,5α,7β,9α,10β,13α‐hexaacetoxytaxa‐4(20),11(12)‐diene (1) as a substrate led to the production of a major oxetane derivative, 1β‐dehydroxybaccatin IV (1 a), and a minor 4β,20‐epoxide derivative, baccatin I (1 b). However, feeding the substrate decinnamoyltaxinine J (2), a 5‐deacetylated derivative of 1, yielded only 5α‐deacetylbaccatin I (2 b), a 4β,20‐epoxide. A possible reaction mechanism was proposed on the basis of substrate‐feeding, 2H and 18O isotope labelling experiments, and density functional theory calculations. This reaction could be an intramolecular oxidation‐acetoxyl rearrangement and the construction of the oxetane ring may occur through a concerted process; however, the 4β,20‐epoxide might be a shunt product. In this process, the C5‐O‐acetyl group in substrate is crucial for the oxetane ring formation but not for the 4(20)‐epoxy ring formation by TmCYP1. These findings provide a better understanding of the enzymatic formation of the oxetane ring in paclitaxel biosynthesis.

  DOI：

  10.1002/anie.202407070
• 作为产物：
  描述：

  triacetoxy-7β,9α,10β trihydroxy-2α,5α,13α taxadiene-4(20),11 在 吡啶 作用下， 反应 68.0h， 生成 hexaacetoxy-2α,5α,7β,9α,10β,13α taxadiene-4(20),11
  参考文献：
  名称：

  Ettouati, Laurent; Ahond, Alain; Convert, Odile, Bulletin de la Societe Chimique de France, 1989, # 5, p. 687 - 694

  摘要：

  DOI：

文献信息

• Characterization and heterologous reconstitution of Taxus biosynthetic enzymes leading to baccatin III
  作者：Bin Jiang、Lei Gao、Haijun Wang、Yaping Sun、Xiaolin Zhang、Han Ke、Shengchao Liu、Pengchen Ma、Qinggang Liao、Yue Wang、Huan Wang、Yugeng Liu、Ran Du、Torben Rogge、Wei Li、Yi Shang、K. N. Houk、Xingyao Xiong、Daoxin Xie、Sanwen Huang、Xiaoguang Lei、Jianbin Yan

  DOI：10.1126/science.adj3484

  日期：2024.2.9

  in paclitaxel oxetane formation, representing a previously unknown enzyme mechanism for oxetane ring formation. We created a screening strategy based on the taxusin biosynthesis pathway and uncovered the enzyme responsible for the taxane oxidation of the C9-position (T9αH). Finally, we artificially reconstituted a biosynthetic pathway for the production of baccatin III in tobacco.

  紫杉醇是一种众所周知的抗癌化合物。其生物合成涉及高度功能化的二萜类核心骨架（浆果赤霉素 III）的形成以及随后苯基异丝氨酸侧链的组装。尽管经过半个世纪的深入研究，浆果赤霉素 III 的完整生物合成途径仍然未知。在这里，我们鉴定了一种双功能细胞色素 P450 酶（紫杉烷氧杂环丁烷酶，TOT），它催化紫杉醇氧杂环丁烷形成中的氧化重排，代表了以前未知的氧杂环丁烷环形成的酶机制。我们创建了基于紫杉素生物合成途径的筛选策略，并发现了负责 C9 位 (T9αH) 紫杉烷氧化的酶。最后，我们人为地重建了在烟草中生产浆果赤霉素 III 的生物合成途径。
• ETTOUATI, LAURENT;AHOND, ALAIN;CONVERT, ODILE;POUPAT, CHRISTIANE;POTIER, +, BULL. SOC. CHIM. FR.,(1989) N, C. 687-694
  作者：ETTOUATI, LAURENT、AHOND, ALAIN、CONVERT, ODILE、POUPAT, CHRISTIANE、POTIER, +

  DOI：——

  日期：——