10-deacetyl-10-ketopaclitaxel | 184291-23-4

• 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: 10-deacetyl-10-ketopaclitaxel
• 英文别名: 10-Oxotaxol；[(1S,2S,3R,4S,7R,9S,10S,15S)-4-acetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11,12-dioxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 184291-23-4
• 化学式: C₄₅H₄₇NO₁₃
• 分子量: 809.867
• InChiKey: CJCYABFPESVRKC-QRTSWCPHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  59
• 可旋转键数：
  12
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  212
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  2'-O-TBDMS-7-O-TES-9,10-diketo-paclitaxel 在 氟化氢吡啶 作用下， 以 吡啶 为溶剂， 反应 3.5h， 以74%的产率得到10-deacetyl-10-ketopaclitaxel
  参考文献：
  名称：

  The Chemistry of the Taxane Diterpene:  Stereoselective Reductions of Taxanes

  摘要：

  Stereoselective reductions of taxanes are detailed. Chelation-controlled reductions employing SmI2 are described for the stereoselective reduction of the 9-keto functionality of the diterpene moiety of several taxanes. In all cases the 9 beta-hydroxy stereochemistry was obtained exclusively. In addition to C9 reduction, partial C10-deoxygenation via beta-elimination was observed. Lower reaction temperatures favored the reduction pathway without beta-elimination. Acetic acid as the proton source gave higher yields and cleaner reaction products. This chemistry provided access to taxanes with 9 beta-hydroxy, 10 beta-hydroxy stereochemistry. Evidence is presented, suggesting that chelation of samarium with the 7 beta-hydroxyl group is required for the reduction of the C9 ketone moiety. The synthesis of paclitaxel analogues, possessing the 9 alpha-hydroxy, 10 alpha-hydroxy stereochemistry was also achieved. Reduction of the 10-ketone group of 10-oxopaclitaxel employing NaBH4 produced 10-deacetyl-10-epipaclitaxel stereoselectively. Using an excess of NaBH4 in this reaction gave exclusively the 9 alpha-hydroxy, 10 alpha-hydroxy paclitaxel analogue.

  DOI：

  10.1021/jo981194s

文献信息

• The Chemistry of the Taxane Diterpene:  Stereoselective Reductions of Taxanes
  作者：Gunda I. Georg、Geraldine C. B. Harriman、Apurba Datta、Syed Ali、Zacharia Cheruvallath、Dinah Dutta、David G. Vander Velde、Richard H. Himes

  DOI：10.1021/jo981194s

  日期：1998.11.1

  Stereoselective reductions of taxanes are detailed. Chelation-controlled reductions employing SmI2 are described for the stereoselective reduction of the 9-keto functionality of the diterpene moiety of several taxanes. In all cases the 9 beta-hydroxy stereochemistry was obtained exclusively. In addition to C9 reduction, partial C10-deoxygenation via beta-elimination was observed. Lower reaction temperatures favored the reduction pathway without beta-elimination. Acetic acid as the proton source gave higher yields and cleaner reaction products. This chemistry provided access to taxanes with 9 beta-hydroxy, 10 beta-hydroxy stereochemistry. Evidence is presented, suggesting that chelation of samarium with the 7 beta-hydroxyl group is required for the reduction of the C9 ketone moiety. The synthesis of paclitaxel analogues, possessing the 9 alpha-hydroxy, 10 alpha-hydroxy stereochemistry was also achieved. Reduction of the 10-ketone group of 10-oxopaclitaxel employing NaBH4 produced 10-deacetyl-10-epipaclitaxel stereoselectively. Using an excess of NaBH4 in this reaction gave exclusively the 9 alpha-hydroxy, 10 alpha-hydroxy paclitaxel analogue.