| 1144034-18-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• CAS: 1144034-18-3
• 化学式: C₂₉H₄₂N₇O₁₈P₃S
• 分子量: 901.676
• InChiKey: UIQUCOQLIVGTTR-SXQYHYLKSA-N

物化性质

• 密度：
  1.80±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

反应信息

• 作为反应物：
  描述：

  、 在 taxane 2-O-benzoyltransferase 作用下， 以 aq. phosphate buffer 为溶剂， 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：

  3-甲氧基苯甲酸 、 NaSCoA 在 三乙胺 、 氯甲酸乙酯 、 碳酸氢钠 作用下， 以 四氢呋喃 、 二氯甲烷 、 叔丁醇 为溶剂， 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

文献信息

• Point Mutations (Q19P and N23K) Increase the Operational Solubility of a 2α-<i>O</i>-Benzoyltransferase that Conveys Various Acyl Groups from CoA to a Taxane Acceptor
  作者：Irosha N. Nawarathne、Kevin D. Walker

  DOI：10.1021/np900524d

  日期：2010.2.26

  Two site-directed Mutations within the wild-type 2-O-benzoyltransferase (tbt) cDNA, from Taxus cuspidata plants, yielded air encoded protein containing replacement amino acids at Q19P and N23K that trial) to a solvent-exposed loop region. The likely significant changes in the biophysical properties invoked by these mutations Caused the overexpressed, modified TBT (mTBT) to partition into the Soluble enzyme fraction about 5-fold greater than the wild-type enzyme. Sufficient protein could now be acquired to examine the scope of the substrate specificity of mTBT by incubation with 7,13-O,O-diacetyl-2-O-debenzoylbaceatin III that was mixed individually with various substituted benzoyls, alkanoyls, and (E)-butenoyl CoA donors. The mTBT catalyzed the conversion of each 7,13-O,O-diacetyl-2-O-debenzoylbaccatin III to several 7,13-O,O-diacetyl-2-O-acyl-2-O-debenzoylbaccatin III analogues. The relative catalytic efficiency of mTBT with the 7,13-O,O-diacetyl-2-O-debenzoyl surrogate Substrate and heterole carbonyl CoA substrates was slightly greater than with the natural aroyl substrate benzoyl CoA, While substituted benzoyl CoA thioesters were less productive. Short-chain hydrocarbon carbonyl and cyclohexanoyl CoA thioesters were also productive, where C-4 Substrates were transferred by mTBT with similar to 10- to 17-fold greater catalytic efficiency compared to the transfer of benzoyl. The described broad specificity of mTBT suggests (flat a plethora of 2-O-acyl variants of the antimitotic paclitaxel can be assembled through biocatalytic sequences.