7-O-acetyl-13-oxobaccatin III | 32981-91-2

• 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: 7-O-acetyl-13-oxobaccatin III
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R)-4,9,12-triacetyloxy-1-hydroxy-10,14,17,17-tetramethyl-11,15-dioxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 32981-91-2
• 化学式: C₃₃H₃₈O₁₂
• 分子量: 626.658
• InChiKey: PHNOBFRCXUABFE-YLKKPXNNSA-N

物化性质

• 沸点：
  714.2±60.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  45
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  169
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  7-O-acetyl-13-oxobaccatin III 在 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 以20 mg的产率得到[13-(3)H]-7-O-acetylbaccatin III
  参考文献：
  名称：

  Point Mutations (Q19P and N23K) Increase the Operational Solubility of a 2α-O-Benzoyltransferase that Conveys Various Acyl Groups from CoA to a Taxane Acceptor

  摘要：

  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.

  DOI：

  10.1021/np900524d
• 作为产物：
  描述：

  10-脱乙酰基巴卡丁 III 在 4-二甲氨基吡啶 、 manganese(IV) oxide 、 三乙胺 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 4.5h， 生成 7-O-acetyl-13-oxobaccatin III
  参考文献：
  名称：

  由 Rh(III) 催化的双 C-H 激活实现的多组分偶联和大环化：H1N1 流感的大环肟抑制剂

  摘要：

  在此，我们描述了一种实用的流线型双组分双 C-H 活化大环化策略，需要原位生成的导向基团。反应模式基于 Rh(III) 催化的三组分偶联，涉及级联 C(sp 3 )–H/C(sp 2)–H键双重激活。该过程通过容易获得的酰胺化试剂，即芳基取代的 1,4,2-二恶唑-5-酮，可以通过铑-氮烯中间体转化为酰胺导向基团来促进。DFT 计算表明，C-N 与 C-C 键形成的化学选择性是高度可控的。各种复杂的天然大环化合物、三萜类化合物、生物活性分子和药物的后期 C-H 官能化突出了这种多组分反应的合成效用。此外，所开发的方法能够方便和多样化地合成复杂的大环内酰胺，表型筛选表明通过该策略获得的几种独特的含肟大环内酰胺显示出强大的抗流感 (H1N1) 活性，没有明显的细胞毒性作用。

  DOI：

  10.1016/j.chempr.2022.10.019

文献信息

• Diastereoselective 14β-Hydroxylation of Baccatin III Derivatives
  作者：Eleonora Baldelli、Arturo Battaglia、Ezio Bombardelli、Giacomo Carenzi、Gabriele Fontana、Andrea Gambini、Maria Luisa Gelmi、Andrea Guerrini、Donato Pocar

  DOI：10.1021/jo0347112

  日期：2003.12.1

  14beta-Hydroxybaccatin III, a compound with limited availability by natural sources, is the starting material for the synthesis of the second-generation anticancer taxoid ortataxel. The 7-tertbutoxycarbonyl. (1a) and 7-triethylsilyl (1b) derivatives of 14beta-hydroxybaccatin III 1,14-carbonate were synthesized from 10-deacetylbaccatin III (3). The crucial steps were (a) the C(14)beta hydroxylation of the corresponding 13-oxobaccatin III derivatives by oxaziridine-mediated electrophilic oxidation and (b) the reduction of the C-13 carbonyl group with sodium or alkylammonium borohydrides. This protocol provides a practical way for the semisynthesis of ortataxel from 10-deacetylbaccatin III, a compound readily available from various yews.
• 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.
• Multicomponent coupling and macrocyclization enabled by Rh(III)-catalyzed dual C–H activation: Macrocyclic oxime inhibitor of influenza H1N1
  作者：Hao Wang、Zhongyu Li、Xiangyang Chen、Jonathan J. Wong、Tongyu Bi、Xiankun Tong、Zhongliang Xu、Mingyue Zhen、Yunhui Wan、Li Tang、Bo Liu、Xinlei Zong、Dandan Xu、Jianping Zuo、Li Yang、Wei Huang、Kendall N. Houk、Weibo Yang

  DOI：10.1016/j.chempr.2022.10.019

  日期：2023.3

  dual C–H activation macrocyclization strategy entailing an in situ-generated directing group. The reaction mode is based on Rh(III)-catalyzed three-component coupling involving cascade C(sp3)–H/C(sp2)–H bond dual activation. The process is facilitated by readily obtainable amidation reagents, namely, aryl-substituted 1,4,2-dioxazol-5-ones, which can be transformed into amide directing groups via a rhodium-nitrene

  在此，我们描述了一种实用的流线型双组分双 C-H 活化大环化策略，需要原位生成的导向基团。反应模式基于 Rh(III) 催化的三组分偶联，涉及级联 C(sp 3 )–H/C(sp 2)–H键双重激活。该过程通过容易获得的酰胺化试剂，即芳基取代的 1,4,2-二恶唑-5-酮，可以通过铑-氮烯中间体转化为酰胺导向基团来促进。DFT 计算表明，C-N 与 C-C 键形成的化学选择性是高度可控的。各种复杂的天然大环化合物、三萜类化合物、生物活性分子和药物的后期 C-H 官能化突出了这种多组分反应的合成效用。此外，所开发的方法能够方便和多样化地合成复杂的大环内酰胺，表型筛选表明通过该策略获得的几种独特的含肟大环内酰胺显示出强大的抗流感 (H1N1) 活性，没有明显的细胞毒性作用。