13-oxobaccatin III | 32981-89-8

• 英文名称: 13-oxobaccatin III
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R)-4,12-diacetyloxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11,15-dioxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 32981-89-8
• 化学式: C₃₁H₃₆O₁₁
• 分子量: 584.62
• InChiKey: WLVIMVFOCWYPHD-KSGSGGQMSA-N

物化性质

• 熔点：
  210-211 °C
• 沸点：
  716.7±60.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  42
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  163
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  13-oxobaccatin III 在 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 15.0h， 生成 (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-4,9,11-trihydroxy-12-((3-methoxybenzoyl)oxy)-4a,8,13,13-tetramethyl-5-oxo-3,4,4a,5,6,9,10,11,12,12a-decahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxete-6,12b(2aH)-diyl diacetate
  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 在 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 N-甲基吲哚酮 、 四丙基高钌酸铵 、 氟化氢吡啶 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 13-oxobaccatin III
  参考文献：
  名称：

  Design, Synthesis and Structure−Activity Relationships of Novel Taxane-Based Multidrug Resistance Reversal Agents

  摘要：

  A series of novel taxane-based multidrug resistance (MDR) reversal agents (TRAs) has been designed and synthesized. Structure-activity relationship (SAR) study clearly indicates that modification of the C-7 position with hydrophobic arenecarbonyleinnamoyl groups brings about high potency against drug efflux mediated by P-glycoprotein (P-gp). Six TRAs exhibit ability to modulate a wide range of ATP-binding cassette (ABC) transporters, such as P-gp, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), which may serve as novel broad-spectrum modulators of ABC transporters.

  DOI：

  10.1021/jm049483y

文献信息

• The chemistry of the taxane diterpene: Stereoselective synthesis of 10-deacetoxy-11,12-epoxypaclitaxel
  作者：Geraldine C.B. Harriman、Ravi K. Jalluri、Gary L. Granewald、David G. Vander Velde、Gunda I. Georg、Richard H. Himes

  DOI：10.1016/0040-4039(95)01928-b

  日期：1995.12

  10-deacetoxypaclitaxel (9) was accomplished with meta-chloroperbenzoic acid leading to a novel pentacyclic ring system. Hydroxyl directed delivery of the epoxidizing agent did not appear to play a role in the stereoselectivity of the reaction as epoxidation occurred at the β-face of the molecule. 10-Deacetoxy-11,12-epoxypaclitaxel (10) proved to be more active than paclitaxel (1) in the microtubule assembly assay and

  用间氯过苯甲酸完成10-deacetoxybaccatin III（6）和10-deacetoxypaclitaxel（9）中烯烃的环氧化反应，产生了新的五环体系。由于在分子的β-面发生环氧化，因此环氧直接引导的环氧化剂似乎没有在反应的立体选择性中起作用。在微管组装试验中，10 -Deacetoxy-11,12-epoxypaclitaxel（10）比紫杉醇（1）更具活性，对紫杉醇对B16黑色素瘤细胞的毒性比紫杉醇低三倍。
• 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.
• A mild and efficient approach for the deprotection of silyl ethers by sodium periodate
  作者：Mijuan Wang、Chun Li、Dali Yin、Xiao-Tian Liang

  DOI：10.1016/s0040-4039(02)02138-x

  日期：2002.11

  A mild and efficient method for the deprotection of silyl ethers is reported. The most often used silyl protecting groups, such as TBDMS, TIPS, TMS, TES, TIBS, TPS can be cleaved by NaIO4 furnishing the corresponding alcohol in high yields. This method can be used for a wide range of substrates. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Antileukemic alkaloids from Taxus wallichiana Zucc
  作者：Roger W. Miller、Richard G. Powell、Cecil R. Smith、Edward Arnold、Jon Clardy

  DOI：10.1021/jo00320a045

  日期：1981.3