7-木糖甙-10-脱乙酰基紫杉醇 | 90332-63-1

• 物质功能分类: 天然产物 - 萜类
• 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
• 中文名称: 7-木糖甙-10-脱乙酰基紫杉醇
• 中文别名: 7-木糖-10-去乙酰基紫杉醇；7-木糖甙-1-脱乙酰基紫杉醇
• 英文名称: 7-O-(β-xylosyl)-10-deacetyltaxol
• 英文别名: 7-β-D-xylosyl-10-deacetyltaxol；7-β-xylosyl-10-deacetylataxol；β-xylosyl-10-deacetyltaxol；7-xylosyl-10-deacetyltaxol；7-(1β-xyloxyl)-10-deacetylpaclitaxel；10-deacetylpaclitaxel-7-xyloside；10-Deacetyl-7-xylosyl Paclitaxel；[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1,12-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(2S,3R,4S,5R)-3,4,5-trihydroxyoxan-2-yl]oxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 90332-63-1
• 化学式: C₅₀H₅₇NO₁₇
• 分子量: 943.999
• InChiKey: ORKLEZFXASNLFJ-DYLQFHMVSA-N

物化性质

• 熔点：
  >228°C (dec.)
• 沸点：
  1068.4±65.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO（轻微、加热、超声处理）、甲醇（轻微、加热、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  68
• 可旋转键数：
  14
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  274
• 氢给体数：
  7
• 氢受体数：
  17

安全信息

• 储存条件：
  2-8℃

制备方法与用途

生物活性

10-Deacetyl-7-xylosyl paclitaxel 是 Paclitaxel（一种微管稳定剂，增强 tubulin 聚合）的衍生物，相比 Paclitaxel 具有更强的药理活性。

靶点

传统细胞毒性药物

化学性质

白色结晶粉末，可溶于甲醇、乙醇和 DMSO 等有机溶剂，来源于红豆杉。

用途

紫杉醇代谢物及杂质，具有抗癌抗肿瘤活性。

反应信息

• 作为反应物：
  描述：

  7-木糖甙-10-脱乙酰基紫杉醇 在 Enterobacter sp. CGMCC 2487 作用下， 生成 10-脱乙酰基巴卡丁 III
  参考文献：
  名称：

  Microbial hydrolysis of 7-xylosyl-10-deacetyltaxol to 10-deacetyltaxol

  摘要：

  Enterobacter sp. CGMCC 2487, a bacterial strain isolated from the soil around a Taxus cuspidata Sieb. et Zucc. plant, was able to remove the xylosyl group from 7-xylosyltaxanes. The xylosidase of this strain was an inducible enzyme. In the bioconversion of 7-xylosyl-10-deacetyltaxol (7-XDT) to 10-deacetyltaxol (10-DT), for the purpose of enhancing the conversion efficiency, the effects of NH4+, oat xylan, temperature, pH value, cell density and substrate concentration on the bioconversion have been systematically investigated. 3.0 mM NH4+, 0.6% oat xylan in the media could enhance the yield of 10-DT; the optimum biocatalytic temperature was 26 degrees C and optimum pH value was 6.0. The highest conversion rate and yield of 10-DT from 7-XDT reached 92% and 764 mg/L, respectively. In addition, the biocatalytic capacity of the cell cultures remained 66.1% after continuous three batches. These results indicate that converting 7-XDT to 10-DT, a useful intermediate for the semisynthesis of paclitaxel or other taxane-based anticancer drugs by a novel bacterial strain, Enterobacter sp. CGMCC 2487, would be an alternative for the practical application in the future. (C) 2010 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molcatb.2010.11.013
• 作为产物：
  描述：

  在 溶剂黄146 、 锌 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以29.5 g的产率得到7-木糖甙-10-脱乙酰基紫杉醇
  参考文献：
  名称：

  一种7-木糖基紫杉醇的制备方法

  摘要：

  本发明涉及一种7‑木糖基紫杉醇的制备方法，属于紫杉烷类抗癌药物的制备技术领域，制备方法包括：S1:7‑木糖基‑10‑去乙酰基紫杉醇浸膏以二氯甲烷和吡啶溶解，搅拌下滴加氯甲酸‑2,2,2‑三氯乙酯，反应得产物I；S2:产物I溶于甲醇和乙酸中，加入锌粉，搅拌反应得产物Ⅱ；S3:产物Ⅱ溶于四氢呋喃中，加入三氯化铈，滴加乙酸酐，搅拌反应，得产物Ⅲ；S4:将产物Ⅲ溶于甲醇中，加入30％二甲胺甲醇溶液，搅拌反应，得7‑木糖基紫杉醇。本发明的优点在于起始物料具有可及性，反应条件温和，目标产物纯度高，能进行大量制备。

  公开号：

  CN113354696B

文献信息

• [EN] SACCHARIDE DERIVATIVE OF A TOXIC PAYLOAD AND ANTIBODY CONJUGATES THEREOF<br/>[FR] DÉRIVÉ DE SACCHARIDE D'UNE CHARGE UTILE TOXIQUE ET CONJUGUÉS D'ANTICORPS DE CELUI-CI
  申请人：GLYKOS FINLAND OY

  公开号：WO2016001485A1

  公开（公告）日：2016-01-07

  A molecule comprising a saccharide bound via an O- glycosidic bond to a hydroxyl group of a toxic payload molecule is disclosed. An antibody-drug conjugate comprising an antibody covalently bound to a toxic payload molecule, optionally via a linker group,and a saccharide bound via an O- glycosidic bond to a hydroxyl group of the toxic payload molecule is further disclosed.

  本文披露了一种分子，其中包括一种糖苷通过O-糖苷键与毒性荷载分子的羟基结合。还披露了一种抗体药物结合物，包括一种抗体与一种毒性荷载分子共价结合，可选地通过连接基团，以及一种糖苷通过O-糖苷键与毒性荷载分子的羟基结合。
• Process for the Preparation of Synthetic Taxanes
  申请人：Tano Dingning

  公开号：US20080287696A1

  公开（公告）日：2008-11-20

  The present invention relates to a process for the preparation of synthetic taxanes, which protects C(7)-OH with lanthanon compounds. Its advantages are simple process and firm & reliable binding. Moreover, no C(7)-acylated taxanes are produced in the subsequent steps, and hydrolysis of C(2′)-ester groups in acylated products becomes readily controllable. In the process for the preparation of synthetic taxanes, tetrahydrofuran is used in the present invention as a medium for acylation, which not only achieves the same effects as pyridine, but also avoids odor, so as to solve the problem regarding the extremely high requirements for the place of production. The present invention can be used for the preparation of not only semi-synthetic taxane using natural taxanes as raw material, but also full-synthetic taxane.

  本发明涉及一种合成紫杉烷类化合物的制备方法，其中使用镧系化合物保护C（7）-OH官能团。本发明具有工艺简单、结合牢固可靠的优点。此外，在后续步骤中不会产生C（7）-酰化紫杉烷类化合物，并且酰化产物中C（2'）-酯基的水解变得容易可控。在合成紫杉烷类化合物的制备过程中，本发明使用四氢呋喃作为酰化介质，不仅能够达到与吡啶相同的效果，而且避免了异味，解决了对生产场所极高要求的问题。本发明既可用于半合成紫杉烷类化合物以天然紫杉烷类化合物为原料的制备，也可用于全合成紫杉烷类化合物的制备。
• Semi-synthesis of paclitaxel from naturally occurring glycosidic precursors
  作者：Koppaka V. Rao

  DOI：10.1002/jhet.5570340255

  日期：1997.3

  Paclitaxel, an antitumor drug effective on ovarian and breast carcinomas, is currently being produced both by direct isolation from the bark of Taxus brevifolia and by semi-synthesis from a natural precursor, 10-deacetyl baccatin III. Although other potential precursors such as 10-deacetyl paclitaxel-7-xyloside were known since 1984, their conversion to paclitaxel could not be achieved because of the

  紫杉醇是一种对卵巢癌和乳腺癌有效的抗肿瘤药物，目前正通过从短叶红豆杉的树皮中直接分离得到两种并由天然前体10-脱乙酰浆果赤霉素III半合成。尽管自1984年以来就知道了其他潜在的前体，例如10-去乙酰基紫杉醇-7-木糖苷，但由于缺乏合适的水解木糖残基的方法，与化合物的稳定性相容，因此无法将其转化为紫杉醇。本文描述了一种方法，该方法使用高碘酸盐，然后是苯肼，以实现10-脱乙酰基紫杉醇-7-木糖苷的去糖基化以形成10-脱乙酰基紫杉醇。另外，通过在与苯肼反应之前包括中间乙酰化步骤，描述了该木糖苷“直接”转化为紫杉醇本身。因为10-去乙酰紫杉醇-7-木糖苷在短叶红豆杉的树皮中的发生率> 0.1％，其成功地水解转化为紫杉醇代表了增加该药物利用率的极其重要的反应。
• Taxane Diterpenoids from the Root Bark of Taiwanese Yew<i>Taxus Mairei</i>
  作者：Ya-Ching Shen、Chaturvedula V. S. Prakash、Meng-Chieh Hung

  DOI：10.1002/jccs.200000151

  日期：2000.10

  10-deacetyltaxol A (5), 10-deacetyl-7-epi-taxol (6), 7-epi-taxol (7), taxol C, 10-deacetyltaxol C, 7β-xylosyl-10-deacetyltaxol (8), taxamairin A (9), taxinine A, 14β-hydroxytaxusin (10), 5α-hydroxy-7β,9α,10β, 13α-tetraacetoxy-4(20), 11-taxadiene, 1-dehydroxybaccatin-VI, 1β-dehydroxybaccatin-IV, baccatin IV, baccatin VI and ponasterone A have been isolated and identified from the root bark of Taxus mairei

  十九种化合物，包括紫杉醇 R (1)、紫杉碱 M (2)、紫杉醇 (3)、紫杉醇 (4)、10-deacetyltaxol A (5)、10-deacetyl-7-epi-taxol (6)、7-epi-紫杉醇 (7), 紫杉醇 C, 10-deacetyltaxol C, 7β-xylosyl-10-deacetyltaxol (8), taxamairin A (9), 紫杉素 A, 14β-hydroxytaxusin (10), 5α-hydroxy-7β,9α,10β, 13α-四乙酰氧基-4(20)、11-紫杉二烯、1-脱羟基浆果赤霉素-VI、1β-脱羟基浆果赤霉素-IV、浆果赤霉素IV、浆果赤霉素VI和松甾酮A已从红豆杉的根皮中分离和鉴定。其中，化合物1是一种新的紫杉类化合物，化合物11和7β-xylosyl-10-deacetyltaxol pentaacetate分别是由
• Cloning and characterization of the β-xylosidase from Dictyoglomus turgidum for high efficient biotransformation of 10-deacetyl-7-xylosltaxol
  作者：Qi Li、Yujie Jiang、Xinyi Tong、Jianjun Pei、Wei Xiao、Zhenzhong Wang、Linguo Zhao

  DOI：10.1016/j.bioorg.2019.103357

  日期：2020.1

  With the aim of finding an extracellular biocatalyst that can efficiently remove the C-7 xylose group from 10-deacetyl-7-xylosltaxol, a Dictyoglomus turgidum beta-xylosidase was cloned and expressed in Escherichia coli BL21 (DE3). The molecular mass of purified Dt-Xyl3 was approximately 84 kDa. The recombinant Dt-Xyl3 was most active at pH 5.0 and 75 degrees C, retaining 88% activity at 65 degrees C for 1 h, and displaying excellent stability over pH 4.0-7.5 for 24 h. In terms of kinetic parameters, the K-m and V-max values for pNPX were 0.8316 mM and 5.0178 mu mol/mL.min, respectively. Moreover, Dt-Xyl3 was activated by Mn(2+)and Ba2+ and inhibited by Cu2+, Ni+ and Al3+. In particular, it displayed high tolerance to salts with 60.8% activity in 20% (w/v) NaCl. Ethanol and methanol at 5-15% showed little effect on the enzymatic activity. Dt-Xyl3 demonstrated multifunctional activities followed by pNPX, pNPAraf and pNPG and had a high selectivity for cleaving the outer xylose moieties of 10-deacetyl-7-xylosltaxol with K-cat/K-m 110.87 s(-1)/mM, which produced 10-deacetyl-taxol to semi-synthesize paclitaxel. Under the optimized conditions (60 degrees C, pH 4.5, enzyme dosage of 0.5 U/mL), 1 g of 10-deacetyl-7-xylosltaxol was transformed to its corresponding aglycone 10-deacetyl-taxol within 30 min, with a molar conversion of 98%. This is the first report that Dictyoglomus turgidum can produce extracellular GH3 beta-xylosidase with highly specific activity for 10-deacetyl-7-xylosltaxol biotransformation, thus leading to the application off beta-xylosidase Dt-Xyl3 as a biocatalyst in biopharmaceutics.