(1S,2R)-ethyl 1,2-dihydroxytetrahydronaphthalene-2-carboxylate | 343868-97-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (1S,2R)-ethyl 1,2-dihydroxytetrahydronaphthalene-2-carboxylate
• 英文别名: ethyl (1S,2R)-1,2-dihydroxy-1,2,3,4-tetrahydronaphthalene-2-carboxylate；ethyl (1S,2R)-1,2-dihydroxy-3,4-dihydro-1H-naphthalene-2-carboxylate
• CAS: 343868-97-3
• 化学式: C₁₃H₁₆O₄
• 分子量: 236.268
• InChiKey: ZRYLOGWATRFFJV-WCQYABFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S,2R)-ethyl 1,2-dihydroxytetrahydronaphthalene-2-carboxylate 在 吡啶 、 ruthenium trichloride 、 sodium periodate 、 氯化亚砜 、 sodium azide 、 四丁基溴化铵 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 3.09h， 生成 (1S,2R)-1-Azido-2-hydroxy-1,2,3,4-tetrahydro-naphthalene-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  Synthesis and NMR-Driven Conformational Analysis of Taxol Analogues Conformationally Constrained on the C13 Side Chain

  摘要：

  Analogues of Taxol (paclitaxel) with the side chain conformationally restricted by insertion of a carbon linker between the 2 ' -carbon and the ortho-position of the 3 ' -phenyl ring were synthesized. Biological evaluation of these new taxoids showed that activity was dependent on the length of the linker and the configuration at C2 ' and C3 '. Two analogues in the home series, 9a and 24a, showed tubulin binding and cytotoxicity comparable to that of Taxol. NAMFIS (NMR analysis of molecular flexibility in solution) deconvolution of the averaged 2-D NMR spectra for 9a yields seven conformations. Within the latter set, the hydrophobically collapsed "nonpolar" and "polar" classes are represented by one conformation each with predicted populations of 12-15%. The five remaining conformers, however, are extended, two of which correspond to the T-conformation (47% of the total population). The latter superimpose well with the recently proposed T-Taxol binding conformer in beta -tubulin. The results provide evidence for the existence of two previously unrecognized structural features that support Taxol-like activity: (1) a reduced torsion angle between C2 ' and C3 ' and (2) an orthogonal arrangement of the mean plane through C1 ', C2 ' and the 2 ' -hydroxyl and the 3 ' -phenyl plane, the latter ring bisected by the former plane. By contrast, epimerization at 2 ' ,3 ' and homologation of the tether to CH2-CH2 were both detrimental for activity. The decreased activity of these analogues is apparently due to configurational and steric factors, respectively.

  DOI：

  10.1021/jm001103v
• 作为产物：
  描述：

  3,4-Dihydronaphthalin-2-carbonsaeure-ethylester 在 甲基磺酰胺 、 AD-mix-α 、 sodium sulfite 作用下， 以 水 、 叔丁醇 为溶剂， 反应 0.25h， 以67%的产率得到(1S,2R)-ethyl 1,2-dihydroxytetrahydronaphthalene-2-carboxylate
  参考文献：
  名称：

  Mitsunobu方法合成旋光性α，α-二取代氨基酸

  摘要：

  已知立体化学构型的手性叔α-羟基酯通过与​​HN 3的Mitsunobu反应转化为α-叠氮基酯。已表明，使用1,1-（偶氮二羰基）二哌啶（ADDP）和三甲基膦（PMe 3）可以在室温下以高化学收率进行该反应的优化。在α-碳处观察到构型完全反转。以高的总化学产率和光学纯度合成了几种α，α-二取代的氨基酸。

  DOI：

  10.1021/ol802325h

文献信息

• Mitsunobu Approach to the Synthesis of Optically Active α,α-Disubstituted Amino Acids
  作者：Jonathan E. Green、David M. Bender、Stona Jackson、Martin J. O’Donnell、James R. McCarthy

  DOI：10.1021/ol802325h

  日期：2009.2.19

  α-azido esters by Mitsunobu reaction with HN3. Optimization of this reaction was shown to proceed at room temperature with high chemical yield using 1,1-(azodicarbonyl)dipiperidine (ADDP) and trimethylphosphine (PMe3). Complete inversion of configuration was observed at the α-carbon. Several α,α-disubstituted amino acids were synthesized in high overall chemical yield and optical purity.

  已知立体化学构型的手性叔α-羟基酯通过与​​HN 3的Mitsunobu反应转化为α-叠氮基酯。已表明，使用1,1-（偶氮二羰基）二哌啶（ADDP）和三甲基膦（PMe 3）可以在室温下以高化学收率进行该反应的优化。在α-碳处观察到构型完全反转。以高的总化学产率和光学纯度合成了几种α，α-二取代的氨基酸。
• Synthesis and NMR-Driven Conformational Analysis of Taxol Analogues Conformationally Constrained on the C13 Side Chain
  作者：Luciano Barboni、Catia Lambertucci、Giovanni Appendino、David G. Vander Velde、Richard H. Himes、Ezio Bombardelli、Minmin Wang、James P. Snyder

  DOI：10.1021/jm001103v

  日期：2001.5.1

  Analogues of Taxol (paclitaxel) with the side chain conformationally restricted by insertion of a carbon linker between the 2 ' -carbon and the ortho-position of the 3 ' -phenyl ring were synthesized. Biological evaluation of these new taxoids showed that activity was dependent on the length of the linker and the configuration at C2 ' and C3 '. Two analogues in the home series, 9a and 24a, showed tubulin binding and cytotoxicity comparable to that of Taxol. NAMFIS (NMR analysis of molecular flexibility in solution) deconvolution of the averaged 2-D NMR spectra for 9a yields seven conformations. Within the latter set, the hydrophobically collapsed "nonpolar" and "polar" classes are represented by one conformation each with predicted populations of 12-15%. The five remaining conformers, however, are extended, two of which correspond to the T-conformation (47% of the total population). The latter superimpose well with the recently proposed T-Taxol binding conformer in beta -tubulin. The results provide evidence for the existence of two previously unrecognized structural features that support Taxol-like activity: (1) a reduced torsion angle between C2 ' and C3 ' and (2) an orthogonal arrangement of the mean plane through C1 ', C2 ' and the 2 ' -hydroxyl and the 3 ' -phenyl plane, the latter ring bisected by the former plane. By contrast, epimerization at 2 ' ,3 ' and homologation of the tether to CH2-CH2 were both detrimental for activity. The decreased activity of these analogues is apparently due to configurational and steric factors, respectively.