2-O-[(2S)-1-[(2S)-2-benzyl-3-methoxy-5-oxo-2H-pyrrol-1-yl]-3-methyl-1-oxobutan-2-yl] 1-O-tert-butyl (2S)-pyrrolidine-1,2-dicarboxylate | 134816-22-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-O-[(2S)-1-[(2S)-2-benzyl-3-methoxy-5-oxo-2H-pyrrol-1-yl]-3-methyl-1-oxobutan-2-yl] 1-O-tert-butyl (2S)-pyrrolidine-1,2-dicarboxylate
• CAS: 134816-22-1
• 化学式: C₂₇H₃₆N₂O₇
• 分子量: 500.592
• InChiKey: KQTMXYXETATGOB-JTAQYXEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-O-[(2S)-1-[(2S)-2-benzyl-3-methoxy-5-oxo-2H-pyrrol-1-yl]-3-methyl-1-oxobutan-2-yl] 1-O-tert-butyl (2S)-pyrrolidine-1,2-dicarboxylate 在 palladium on activated charcoal 氰基磷酸二乙酯 、 氢气 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 39.0h， 生成 dolastatin 15
  参考文献：
  名称：

  The Dolastatins 20. A Convenient Synthetic Route to Dolastatin 15

  摘要：

  A segment synthetic strategy was utilized for obtaining the Dolabella auricularia (Indian Ocean sea hare) depsipeptide dolastatin 15. Reaction of protected (S)-Hiva-(S)-Phe 2c with isopropenyl chloroformate followed by Meldrum's ester, cyclization (2c --> 3a) of the product in toluene and finally methylation afforded the key (S)-dolapyrrolidine (Dpy) derivative 3b. Condensation of tripeptide 8 with the three unit Dpy segment 5b followed by deprotection and coupling (diethyl phosphorocyanidate) led to dolastatin 15 in 11% overall yield. The powerful and selective activity of dolastatin 15 against the U.S. National Cancer Institute's panel of human cell lines has been summarized.

  DOI：

  10.1016/s0040-4020(01)89562-4
• 作为产物：
  描述：

  N-<(2S)-O-tert-butyldimethylsilyl-2-hydroxy-isovaleryl>-L-phenylalanine 在 4-二甲氨基吡啶 、 potassium carbonate 、 4-吡咯烷基吡啶 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 25.0h， 生成 2-O-[(2S)-1-[(2S)-2-benzyl-3-methoxy-5-oxo-2H-pyrrol-1-yl]-3-methyl-1-oxobutan-2-yl] 1-O-tert-butyl (2S)-pyrrolidine-1,2-dicarboxylate
  参考文献：
  名称：

  The Dolastatins 20. A Convenient Synthetic Route to Dolastatin 15

  摘要：

  A segment synthetic strategy was utilized for obtaining the Dolabella auricularia (Indian Ocean sea hare) depsipeptide dolastatin 15. Reaction of protected (S)-Hiva-(S)-Phe 2c with isopropenyl chloroformate followed by Meldrum's ester, cyclization (2c --> 3a) of the product in toluene and finally methylation afforded the key (S)-dolapyrrolidine (Dpy) derivative 3b. Condensation of tripeptide 8 with the three unit Dpy segment 5b followed by deprotection and coupling (diethyl phosphorocyanidate) led to dolastatin 15 in 11% overall yield. The powerful and selective activity of dolastatin 15 against the U.S. National Cancer Institute's panel of human cell lines has been summarized.

  DOI：

  10.1016/s0040-4020(01)89562-4

文献信息

• Synthesis and Biological Activity of Chimeric Structures Derived from the Cytotoxic Natural Compounds Dolastatin 10 and Dolastatin 15
  作者：Joël Poncet、Magali Busquet、Florence Roux、Alain Pierré、Ghanem Atassi、Patrick Jouin

  DOI：10.1021/jm970800t

  日期：1998.4.1

  The natural cytotoxic compounds dolastatins 10 and 15 exhibit great similarities in structure and in their biological activity profiles. Two compounds (1 and 2) formed by interchanging the dolaisoleuine residue of dolastatin 10 and the MeVal-Pro dipeptide of dolastatin 15 were synthesized in order to evaluate the possible equivalence of these units. These compounds can be considered as chimeras of dolastatins 10 and 15 formed by the N-terminal part of the former and the C-terminal part of the latter and vice versa. Both analogues exhibited a marked decrease in their cytotoxic activity but showed similar differential cytotoxicity with regard to the cell Lines assayed compared with the parent compounds. HT-29 cell line was the least sensitive one. However, this activity was in the nanomolar level and close to that of vincristine. The differences in their effect on tubulin polymerization were less pronounced. We confirmed the already known crucial role of the Dil residue in this assay. The nonequivalence of the Dil unit and the MeVal-Pro dipeptide probably reflects modification in the relative positions of the N-dimethylamino and the phenyl moieties.
• Pettit, George R.; Herald, Delbert L.; Singh, Sheo Bux, Journal of the American Chemical Society, 1991, vol. 113, # 17, p. 6692 - 6693
  作者：Pettit, George R.、Herald, Delbert L.、Singh, Sheo Bux、Thornton, Timothy J.、Mullaney, Jeffrey T.

  DOI：——

  日期：——
• PETTIT, GEORGE R.;HERALD, DELBERT L.;SINGH, SHEO BUX;THORNTON, TIMOTHY J.+, J. AMER. CHEM. SOC., 113,(1991) N7, C. 6692-6693
  作者：PETTIT, GEORGE R.、HERALD, DELBERT L.、SINGH, SHEO BUX、THORNTON, TIMOTHY J.+

  DOI：——

  日期：——
• Convergent Synthesis of Dolastatin 15 by Solid Phase Coupling of an <i>N</i>-Methylamino Acid
  作者：Kenichi Akaji、Yuzo Hayashi、Yoshiaki Kiso、Naohiro Kuriyama

  DOI：10.1021/jo981055a

  日期：1999.1.1

  Convergent synthesis of dolastatin 15 (1), a cytostatic depsipeptide isolated from the Indian Ocean sea hare, has been described. For construction of the backbone, a single-step condensation of peptide fragment 2 and pyrrolidone fragment 3 was successfully performed using 2-chloro-1,3-dimethyl-2-imidazolinium hexafluorophosphate (CIP) developed by us as an efficient coupling reagent. Coupling of an N-methylamino acid on solid support was first achieved using CTP for the efficient synthesis of peptide fragment 2. The effectiveness of CIP for the coupling of N-methylamino acids in solution and on solid support were clarified by the syntheses of model di- and tripeptides.
• The Dolastatins 20. A Convenient Synthetic Route to Dolastatin 15
  作者：George R. Pettit、Timothy J. Thornton、Jeffrey T. Mullaney、Michael R. Boyd、Delbert L. Herald、Sheo-Bux Singh、Erik J. Flahive

  DOI：10.1016/s0040-4020(01)89562-4

  日期：1994.1

  A segment synthetic strategy was utilized for obtaining the Dolabella auricularia (Indian Ocean sea hare) depsipeptide dolastatin 15. Reaction of protected (S)-Hiva-(S)-Phe 2c with isopropenyl chloroformate followed by Meldrum's ester, cyclization (2c --> 3a) of the product in toluene and finally methylation afforded the key (S)-dolapyrrolidine (Dpy) derivative 3b. Condensation of tripeptide 8 with the three unit Dpy segment 5b followed by deprotection and coupling (diethyl phosphorocyanidate) led to dolastatin 15 in 11% overall yield. The powerful and selective activity of dolastatin 15 against the U.S. National Cancer Institute's panel of human cell lines has been summarized.