10-O-propionyl-10-O-deacetylbaccatin III | 220647-31-4

• 英文名称: 10-O-propionyl-10-O-deacetylbaccatin III
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1,9,15-trihydroxy-10,14,17,17-tetramethyl-11-oxo-12-propanoyloxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 220647-31-4
• 化学式: C₃₂H₄₀O₁₁
• 分子量: 600.663
• InChiKey: ULLFGYLDOACNCF-MNVLTVTDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.04
• 重原子数：
  43.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  165.89
• 氢给体数：
  3.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  10-O-propionyl-10-O-deacetylbaccatin III 在 manganese(IV) oxide 、 sodium tetrahydroborate 、 taxane 2-O-benzoyltransferase 、 辅酶 A 作用下， 以 四氢呋喃 、 甲醇 、 aq. phosphate buffer 为溶剂， 反应 23.0h， 生成
  参考文献：
  名称：

  Biocatalytic and Regioselective Exchange of 2‐O‐Benzoyl for 2‐O‐(m‐Substituted)Benzoyl Groups to Make Precursors of Next‐Generation Paclitaxel Drugs

  摘要：

  A taxane 2‐O‐benzoyltransferase (mTBT, derived from Accession: AF297618) biocatalyzed the dearoylation and rearoylation of next‐generation taxane precursors of drugs effective against multidrug‐resistant cancer cells. Various taxanes bearing an acyl, hydroxyl, or oxo group at C13 were screened to assess their turnover by mTBT catalysis. The 13‐oxotaxanes were the most productive, where 2‐O‐debenzoylation of 13‐oxobaccatin III was turned over faster compared to 13‐oxo‐10‐O‐(n‐propanoyl)‐10‐O‐deacetylbaccatin III and 13‐oxo‐10‐O‐(cyclopropane carbonyl)‐10‐O‐deacetylbaccatin III, yielding ~20 mg of each. mTBT catalysis was likely affected by an intramolecular hydrogen bond with the C13−hydroxyl. Oxidation to the 13‐oxo recovered catalysis. The experimental data for the debenzoylation reaction was supported by Gaussian‐accelerated molecular dynamics simulations that evaluated the conformational changes caused by different functional groups at C13 of the substrate. These findings also helped postulate where the 2‐O‐benzoylation reaction occurs on the paclitaxel pathway in nature. mTBT rearoylated the debenzoylated 13‐oxobaccatin III acceptors fastest with a non‐natural 3‐fluorobenzoyl CoA among the other aroyl CoA thioesters evaluated, yielding ~10 mg of each with excellent regioselectivity at laboratory scale. Reducing the 13‐oxo group to a hydroxyl yielded key modified baccatin III precursors (~10 mg at laboratory scale) of new‐generation taxoids.

  DOI：

  10.1002/cctc.202400186
• 作为产物：
  描述：

  10-脱乙酰基巴卡丁 III 、 丙酸酐 在 cerium(III) chloride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 10-O-propionyl-10-O-deacetylbaccatin III
  参考文献：
  名称：

  C-3'NH / C-10和C-2 / C-10修饰的紫杉醇类似物的合成和生物学评估。

  摘要：

  同时研究了紫杉醇在C-3'NH / C-10和C-2 / C-10位置上的修饰，以研究可能的协同作用。在微管组装试验和人卵巢癌（A2780）和前列腺癌（PC3）细胞毒性试验中评估了这些类似物的生物学活性。在某些情况下，双修饰的类似物比基于单修饰的类似物的活性所预测的活性更高，表明可能具有协同作用。

  DOI：

  10.1016/s0968-0896(02)00608-9

文献信息

• Biocatalysis of precursors to new-generation SB-T-taxanes effective against paclitaxel-resistant cancer cells
  作者：Aimen Al-Hilfi、Kevin D. Walker

  DOI：10.1016/j.abb.2022.109165

  日期：2022.4