紫杉醇缩合物 | 158722-23-7

• 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: 紫杉醇缩合物
• 中文别名: 紫杉醇缩合物(N-1步的紫杉醇)
• 英文名称: 7-(triethylsilyl)-13-O-[((4S,5R)-2,4-diphenyl-4,5-dihydrooxazol-5-yl)carbonyl]baccatin
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-2-benzoyloxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-triethylsilyloxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-15-yl] (4S,5R)-2,4-diphenyl-4,5-dihydro-1,3-oxazole-5-carboxylate
• CAS: 158722-23-7
• 化学式: C₅₃H₆₃NO₁₃Si
• 分子量: 950.168
• InChiKey: ZAXCJOQYACAQIY-RGZLSWIJSA-N

物化性质

• 熔点：
  211-212 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  893.9±65.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.82
• 重原子数：
  68
• 可旋转键数：
  17
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  183
• 氢给体数：
  1
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  紫杉醇缩合物 在 水 、 potassium hydrogencarbonate 、 氟化氢吡啶 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 为溶剂， 反应 19.17h， 生成 2'-deoxy-2'-epi-mercaptopaclitaxel
  参考文献：
  名称：

  C-13侧链含硫基的新型紫杉烷类似物的合成：2'-脱氧-2'-表位-巯基紫杉醇

  摘要：

  在C-13侧链的羟基上具有巯基的紫杉醇类似物为研究新的紫杉类化合物提供了一条有趣的研究途径。已开发出制备具有高ee的2'-脱氧-2'- epi-巯基紫杉醇的合成途径。关键步骤是反式-恶唑啉衍生物与硫代乙酸的区域控制的开环反应，该反应允许将含硫基团引入侧链。

  DOI：

  10.1016/s0040-4020(03)01098-6
• 作为产物：
  描述：

  (Z,3E)-1-[[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-2-benzoyloxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-12-phenylmethoxycarbonyloxy-9-triethylsilyloxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-15-yl]oxy]-2-diazonio-3-phenyl-3-phenylmethoxyiminoprop-1-en-1-olate 在 palladium on activated charcoal 4-二甲氨基吡啶 、 copper acetylacetonate 、 甲酸铵 、 双(二丁基氯基锡(四))氧化物 、 sodium cyanoborohydride 、 碳酸氢钠 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 吡啶 、 乙醇 、 溶剂黄146 为溶剂， 反应 101.0h， 生成 紫杉醇缩合物
  参考文献：
  名称：

  通过带有β-酮酸酯附件的10-去乙酰基浆果赤霉素III衍生物半合成紫杉醇

  摘要：

  从新开发的在C-13上带有β-酮酯附件的浆果赤霉素III衍生物开始成功地完成了紫杉醇的半合成。

  DOI：

  10.1016/s0040-4039(99)02056-0

文献信息

• [EN] THE METHOD FOR PRODUCTION OF SEMI-FINISHED PRODUCTS USEFUL IN SYNTHESIS OF PACLITAXEL<br/>[FR] PROCEDE DE PRODUCTION DE PRODUITS SEMI-FINIS UTILES DANS LA SYNTHESE DU PACLITAXEL
  申请人：AGROPHARM S A

  公开号：WO2004056790A1

  公开（公告）日：2004-07-08

  The method for production of the semi-finished products useful in synthesis of Paclitaxel with the generalized formula (2), characterized in that phenyl isoserine derivatives, or mixtures of their epimerides with various configurations on the carbon 2' or their salts, are treated with triazine type condensing agent, possible in the presence of tertiary amine, in medium of anhydrous organic solvent, and the triazine esters produced are treated with Baccatin III, in medium of anhydrous organic solvent, possible in the presence of a catalyst.

  生产半成品，用于合成通式（2）的紫杉醇的方法，其特征在于将苯基异丝氨酸衍生物或其在碳2'上具有不同构型的表异构体混合物或其盐与三嗪类缩合剂在无水有机溶剂中处理，可能在三级胺的存在下进行，并将产生的三嗪酯在无水有机溶剂中处理，可能在催化剂的存在下，与紫杉醇III处理。
• Synthesis of taxol from baccatin III via an oxazoline intermediate
  作者：David G.I. Kingston、Ashok G. Chaudhary、A.A.Leslie Gunatilaka、Mark L. Middleton

  DOI：10.1016/s0040-4039(00)60706-2

  日期：1994.6

  Taxol (1) can be prepared in good yield by coupling the oxazoline carboxylic acid 5 with 7-(triethylsilyl)baccatin III, followed by hydrolysis. The oxazolines 7 and 8 can also be prepared directly from taxol.

  通过将恶唑啉羧酸5与7-（三乙基甲硅烷基）浆果赤霉素III偶联，然后水解，可以以高收率制备紫杉醇（1）。恶唑啉7和8也可以直接由紫杉醇制备。
• A New Semisynthesis of Paclitaxel from Baccatin III
  作者：Erkan Baloglu、David G. I. Kingston

  DOI：10.1021/np990040k

  日期：1999.7.1

  A new method for the semisynthesis of paclitaxel (Taxol) from baccatin III via a dioxo-oxathiazolidine intermediate is reported.

  报道了一种新的方法，可通过二氧杂-氧杂噻唑烷中间体从浆果赤霉素Ⅲ中半合成紫杉醇（Taxol）。
• Synthesis of novel thiol surrogate of Taxol®: 2′-deoxy-2′-mercaptopaclitaxel
  作者：Xin Qi、Sang-Hyeup Lee、Juyoung Yoon、Yoon-Sik Lee

  DOI：10.1016/j.tet.2004.02.047

  日期：2004.4

  C-13 side chain constitute an interesting avenue of research for the study of new taxoid compounds. A synthetic route for the preparation of the exact thiol surrogate product of Taxol® by coupling (4S, 5S)-2,4-diphenyloxazoline-5-carboxylic acid with 7-triethylsilyl baccatin III, followed by ring-opening of the oxazoline intermediate with thiolacetic acid is described.

  在C-13侧链的羟基上具有巯基的紫杉醇类似物为研究新的紫杉类化合物提供了一条有趣的研究途径。紫杉醇的确切硫醇替代产品的制备的合成路线®通过偶合（4小号，5小号）-2,4-二苯基恶唑啉-5-羧酸与7-三乙基甲硅烷基浆果赤霉素Ⅲ，接着恶唑啉开环描述了与硫代乙酸的中间体。
• Taxol Semisynthesis:  A Highly Enantio- and Diastereoselective Synthesis of the Side Chain and a New Method for Ester Formation at C-13 Using Thioesters
  作者：Cesare Gennari、Michela Carcano、Monica Donghi、Nicola Mongelli、Ermes Vanotti、Anna Vulpetti

  DOI：10.1021/jo9703212

  日期：1997.7.1

  A very simple, new, and straightforward approach to the Paclitaxel (Taxol) and Docetaxel (Taxotere) side chains has been developed using the imine addition reaction of thioester-derived boron enolates bearing chiral ligands. The addition reaction was studied extensively, using a combination of different thioesters (ROCH2COSPh, ROCH(2)60St-Bu), oxygen protecting groups (R = Bn, TBDMS, COPh, EE, TMS), chiral boron ligands [derived from both (-) and (+)-menthone], imines (PhCH=NSiMe3, PhCH=NCOPh), and in the presence or in the absence of additional Lewis acids (BF3-OEt2, Et2AlCl, TiCl4). The side chain was assembled in a few steps with the correct relative (syn) and absolute stereochemistry (2R,3S). The stereochemical outcome of the boron-mediated reaction was rationalized using chair vs boat transition state structures. A new direct route for attachment of the side chains to the baccatin nucleus using thioester chemistry has also been developed. By treatment of a mixture of a thioester (8, 12, or 17) and protected baccatin III (2b, 2c) with LHMDS, the 13-O acylated compounds were obtained in high yield (up to 90%). Hydrolysis of 18b gave Paclitaxel (1a) in 80% yield.