2'-O-(叔-丁基二甲基硅烷基)-6alpha-羟基7-表-紫杉醇 | 165065-08-7

• 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: 2'-O-(叔-丁基二甲基硅烷基)-6alpha-羟基7-表-紫杉醇
• 中文别名: 2'-O-(叔-丁基二甲基硅烷基)-6α-羟基7-表-紫杉醇
• 英文名称: 2'-O-(tert-butyldimethylsilyl)-6α-hydroxy-7-epipaclitaxel
• 英文别名: 2'-TBDMS-6α-hydroxy-7-epipaclitaxel；2'-O-(t-butyldimethylsilyl)-6α-hydroxy-7-epi-paclitaxel；2'-O-(tert-Butyldimethylsilyl)-6alpha-hydroxy-7-epi-paclitaxel；[(1S,2S,3R,4S,7R,8S,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoyl]oxy-1,8,9-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 165065-08-7
• 化学式: C₅₃H₆₅NO₁₅Si
• 分子量: 984.182
• InChiKey: ACJHNDYFTFXEOF-QTYAFJNESA-N

物化性质

• 溶解度：
  可溶于氯仿、二氯甲烷、乙酸乙酯、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  5.74
• 重原子数：
  70
• 可旋转键数：
  17
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  231
• 氢给体数：
  4
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  2'-O-(叔-丁基二甲基硅烷基)-6alpha-羟基7-表-紫杉醇 在 lead(IV) acetate 、 碳酸氢钠 作用下， 以 苯 为溶剂， 生成 2'-TBDMS-C-norpaclitaxel
  参考文献：
  名称：

  Synthesis of novel taxol analogs and evaluation of their biological activities

  摘要：

  Two new taxol analogs 6 and 10 have been prepared from baccatin III (1) and taxol (7a), respectively. Like taxol, both compounds were found to promote microtubule formation and stabilization, although they were less active than taxol. Both 6 and 10 exhibited cytotoxicity against J774.2 cells; 6 was similar to 60-fold less active and 10 was similar to 15-fold less active. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00337-5
• 作为产物：
  描述：

  2'-O-(叔-丁基二甲基硅烷基)紫杉醇7-O-三氟甲烷磺酸酯 在 四氧化锇 、 N-甲基吗啉氧化物 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 叔丁醇 为溶剂， 反应 13.0h， 生成 2'-O-(叔-丁基二甲基硅烷基)-6alpha-羟基7-表-紫杉醇
  参考文献：
  名称：

  Paclitaxel analogs modified in ring C: Synthesis and biological evaluation

  摘要：

  Lead tetracetate oxidation of 6 alpha-hydroxy-7-epi-paclitaxel leads to C-nor-paclitaxel and C-seco-paclitaxel derivatives. Tetrapropylammonium permthenate (TPAP) oxidation of a 6 alpha-hydroxy-7-epi-paclitaxel derivative leads to a 6-formyl-C-nor-paclitaxel derivative. Reaction of a 6 alpha-O-trifluoromethanesulfonyl-7-epi-paclitaxel derivative with DMAP yields a 20-O-acetyl-4-deacetyl-5,6-dehydro-6-formyl-C-nor-paclitaxel derivative. C-nor-paclitaxel analogs are less active than paclitaxel. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4020(97)00074-4

文献信息

• Synthesis and Biological Activity of C-6 and C-7 Modified Paclitaxels
  作者：Haiqing Yuan、Craig R Fairchild、Xian Liang、David G.I Kingston

  DOI：10.1016/s0040-4020(00)00611-6

  日期：2000.8

  C-7 positions has been achieved using the readily available intermediate 6α-hydroxy-7-epipaclitaxel (2). While a single diastereomer of the cyclic sulfite of 2 was prepared at lower temperature, both diastereomers were obtained at room temperature. The cyclic sulfate was found to be inert toward nucleophilic attack, which confirms the great steric hindrance of the β-face of the C-6 and C-7 region of

  紫杉醇在C-6和C-7位置的结构修饰已通过使用容易获得的中间体6α-羟基-7-外表紫杉醇（2）实现。虽然在较低的温度下制备了2的环状亚硫酸盐的单一非对映异构体，但在室温下却获得了两种非对映异构体。发现该环状硫酸盐对亲核攻击是惰性的，这证实了紫杉醇C-6和C-7区域的β面的巨大空间位阻。使用交替的底物6α-三氟甲磺酸盐（9）和7-表位原子完成了具有含氮功能的6β位衍生化反应保护羟基以避免形成C环重排产物。6β-叠氮化物的氢化是困难的，但是可以在高压下以中等收率实现。与先前报道的其他C-6和C-7修饰类似物相似，这些新化合物对紫杉醇针对HCT116人结肠癌细胞系和A2780人乳腺癌细胞系显示出相当的体外细胞毒性。
• Synthesis, structure elucidation and biological evaluation of C-norpaclitaxel
  作者：Xian Liang、David G.I. Kingston、Byron H. Long、Craig A. Fairchild、Kathy A. Johnston

  DOI：10.1016/0040-4039(95)01650-7

  日期：1995.10

  2′-TBDMS-6α-hydroxy-7-epipaclitaxel (1) with lead tetraacetate furnished 2′-TBDMS-C-norpaclitaxel (2) and the C-seco compound 3. Deprotection of 2 with pyridinium hydrofluoride yielded Cnorpaclitaxel (4). C-norpaclitaxel (4) is less effective at promoting the assembly of microtubules and less cytotoxic towards HCT116 cells than paclitaxel.

  用四乙酸铅将2'-TBDMS-C-正紫杉醇（2）和C-seco化合物氧化2'-TBDMS-6α-羟基-7-表紫杉醇（1）和C-seco化合物3。用氢氟吡啶鎓对2进行脱保护得到Cnorpaclitaxel（4）。与紫杉醇相比，C-诺紫杉醇（4）在促进微管组装方面效果不佳，对HCT116细胞的细胞毒性也较小。
• Synthesis and biological evaluation of paclitaxel analogs modified in ring C
  作者：Xian Liang、David G.I. Kingston、Chii M. Lin、Ernest Hamel

  DOI：10.1016/0040-4039(95)00431-b

  日期：1995.4

  Both 7-deoxy-7 alpha-azidopaclitaxel (6) and 7-deoxy-Delta(6,7)-paclitaxel (4) can be prepared from paclitaxel-7-0-triflate (2b). Oxidation of 7-deoxy-Delta(6,7)-paclitaxel with dioxirane yields the epoxide 7, while oxidation with osmium tetroxide yields 6 alpha-hydroxy-7-epipaclitaxel (9), and acylation of this gives the 6 alpha-acyloxy-7-epipaclitaxel derivatives 11a-d. No compound was as effective at promoting tubulin assembly as paclitaxel, but most stabilized polymer as well as or better than paclitaxel. Compounds 4, 6, 7, 9, and 11d differed little from paclitaxel in their cytotoxicity for human Burkitt lymphoma CA46 cells.
• Synthesis of 6α-hydroxypaclitaxel, the major human metabolite of paclitaxel
  作者：Haiqing Yuan、David G.I. Kingston

  DOI：10.1016/s0040-4039(98)00970-8

  日期：1998.7

  6 alpha-Hydroxypaclitaxel, the major human metabolite of paclitaxel, was synthesized via epimerization of 6 alpha-hydroxy-7-epipaclitaxel, which was prepared from paclitaxel ill four steps in high yield. Various epimerization conditions were investigated, and the optimum conditions using DBU in xylenes afforded 80-88% isolated yield based on unrecovered starting material, along with 4-deacetyl analogs as minor products. The stereochemistry of paclitaxel 6,7-epoxide was revised in the course of this work. (C) 1998 Elsevier Science Ltd. All rights reserved.
• An interesting c-ring contraction in paclitaxel (Taxol®)
  作者：Shu-Hui Chen、Stella Huang、Gregory P. Roth

  DOI：10.1016/0040-4039(95)01954-g

  日期：1995.12

  An interesting pinacol rearrangement involving 7-epi-6 alpha-tosylate/triflate-paclitaxel derivatives (6) and (10), with the formation of five-membered C-ring containing analogs (7) and (11), is described.