methyl (4S,5S)-2-((S)-1-((tert-butoxycarbonyl)amino)-2-methylpropyl)-5-methyl-4,5-dihydrooxazole-4-carboxylate | 159830-03-2

• 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: methyl (4S,5S)-2-((S)-1-((tert-butoxycarbonyl)amino)-2-methylpropyl)-5-methyl-4,5-dihydrooxazole-4-carboxylate
• 英文别名: methyl (4S,5S)-5-methyl-2-[(1S)-2-methyl-1-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]-4,5-dihydro-1,3-oxazole-4-carboxylate
• CAS: 159830-03-2
• 化学式: C₁₅H₂₆N₂O₅
• 分子量: 314.382
• InChiKey: MDAWCDBOPIJGSR-DCAQKATOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  86.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (4S,5S)-2-((S)-1-((tert-butoxycarbonyl)amino)-2-methylpropyl)-5-methyl-4,5-dihydrooxazole-4-carboxylate 在 三氯溴甲烷 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 以93%的产率得到2-<(S)-1--2-methylpropyl>-5-methyl-4-carbomethoxyoxazole
  参考文献：
  名称：

  Synthesis of libraries of thiazole, oxazole and imidazole-based cyclic peptides from azole-based amino acids. A new synthetic approach to bistratamides and didmolamides

  摘要：

  将噻唑类氨基酸8a和8b的1:1混合物与FDPP-i-Pr2NEt在CH3CN中处理，得到了环状三聚体14、15、16和17以及环状四聚体19和23的混合物，其比例为2:7:5:8:1:1，总产率为70%。在FDPP-i-Pr2NEt存在下，双咪唑氨基酸45与噻唑/噁唑氨基酸43a和42a分别进行的单独偶联反应，分别得到了双咪唑基环状三聚体55和57（产率54-57%）以及环状四聚体56（产率8-11%）。类似地，双噻唑和双噁唑氨基酸49和47与咪唑/噁唑/噻唑氨基酸41a、42a和43a进行的偶联反应，生成了噁唑、噻唑和咪唑基环状肽库58、59、60、61、62、63、64和65。双噻唑氨基酸49与噁唑氨基酸73之间的偶联反应，高效（总产率36%）合成了在海鞘Lissoclinum bistratum中发现的双层板H（67）。含有噻唑氨基酸的噁唑啉的偶联反应效果较差。因此，苯丙氨酸基噁唑啉氨基酸71a与噻唑氨基酸8a或双噻唑氨基酸74之间的偶联反应，仅得到了在海鞘Didemnum molle中发现的环状六肽didmolamide A（4），产率仅为2%。使用FDPP或DPPA，从74与苯丙氨酸苏氨酸氨基酸72的偶联反应中获得了产率为9%的didmolamide B（68）。

  DOI：

  10.1039/b701999h
• 作为产物：
  描述：

  Boc-Val-Thr-OMe 在 二乙胺基三氟化硫 、 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 2.58h， 以89%的产率得到methyl (4S,5S)-2-((S)-1-((tert-butoxycarbonyl)amino)-2-methylpropyl)-5-methyl-4,5-dihydrooxazole-4-carboxylate
  参考文献：
  名称：

  In pursuit of balgacyclamide A – Discovery of an oxazoline macrocycle with multiple myeloma cytotoxicity and penetration

  摘要：

  Four new oxazoline based macrocycles have been constructed, said cycles were found to possess varying cytotoxicity against six different cancer cell lines: IC50 values of 6.4 mu M towards HeLa and 11.9 mu M towards LnCaP being the most potent. Two of the four macrocycles were found to have marginal cytotoxicity against MM.1S and MM.1R, myeloma cancer cell lines, and further evaluation showed that they also possessed rapid cellular uptake and accumulation characteristics. Through the structure-activity relationship comparisons between the four compounds, it was found that the C6 position of the E-ring is amendable to substitution and could possibly serve as a conjugation site for the development of a selective delivery system to MM.1R. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2017.09.071

文献信息

• Synthesis of libraries of thiazole, oxazole and imidazole-based cyclic peptides from azole-based amino acids. A new synthetic approach to bistratamides and didmolamides
  作者：Anna Bertram、Nakia Maulucci、Olivia M. New、Siti Mariam Mohd Nor、Gerald Pattenden

  DOI：10.1039/b701999h

  日期：——

  Treatment of a 1 : 1 mixture of the thiazole-based amino acids 8a and 8b with FDPP–i-Pr2NEt in CH3CN gave a mixture of the cyclic trimers 14, 15, 16 and 17 and the cyclic tetramers 19 and 23 in the ratio 2 : 7 : 5 : 8 : 1 : 1 and in a combined yield of 70%. Separate coupling reactions between the bisimidazole amino acid 45 and the thiazole/oxazole amino acids 43a and 42a in the presence of FDPP–i-Pr2NEt led to the bisimidazole based cyclic trimers 55 and 57 respectively (54–57%) and to the cyclic tetramer 56 (8–11%). Similar coupling reactions involving the bisthiazole and bisoxazole amino acids 49 and 47 with the imidazole/oxazole/thiazole amino acids 41a, 42a and 43a gave rise to the library of oxazole, thiazole and imidazole-based cyclic peptides 58, 59, 60, 61, 62, 63, 64 and 65. A coupling reaction between the bisthiazole amino acid 49 and the oxazole amino acid 73 led to an efficient (36% overall) synthesis of bistratamide H (67) found in the ascidian Lissoclinum bistratum. Coupling reactions involving oxazolines with thiazole amino acids were less successful. Thus, a coupling reaction between the phenylalanine-based oxazoline amino acid 71a and either the thiazole amino acid 8a or the bisthiazole amino acid 74 gave only a 2% yield of the cyclic hexapeptide didmolamide A (4) found in the ascidian Didemnum molle. Didmolamide B (68) was obtained in 9% yield from a coupling reaction between 74 and the phenylalanine threonine amino acid 72, using either FDPP or DPPA.

  将噻唑类氨基酸8a和8b的1:1混合物与FDPP-i-Pr2NEt在CH3CN中处理，得到了环状三聚体14、15、16和17以及环状四聚体19和23的混合物，其比例为2:7:5:8:1:1，总产率为70%。在FDPP-i-Pr2NEt存在下，双咪唑氨基酸45与噻唑/噁唑氨基酸43a和42a分别进行的单独偶联反应，分别得到了双咪唑基环状三聚体55和57（产率54-57%）以及环状四聚体56（产率8-11%）。类似地，双噻唑和双噁唑氨基酸49和47与咪唑/噁唑/噻唑氨基酸41a、42a和43a进行的偶联反应，生成了噁唑、噻唑和咪唑基环状肽库58、59、60、61、62、63、64和65。双噻唑氨基酸49与噁唑氨基酸73之间的偶联反应，高效（总产率36%）合成了在海鞘Lissoclinum bistratum中发现的双层板H（67）。含有噻唑氨基酸的噁唑啉的偶联反应效果较差。因此，苯丙氨酸基噁唑啉氨基酸71a与噻唑氨基酸8a或双噻唑氨基酸74之间的偶联反应，仅得到了在海鞘Didemnum molle中发现的环状六肽didmolamide A（4），产率仅为2%。使用FDPP或DPPA，从74与苯丙氨酸苏氨酸氨基酸72的偶联反应中获得了产率为9%的didmolamide B（68）。
• In pursuit of balgacyclamide A – Discovery of an oxazoline macrocycle with multiple myeloma cytotoxicity and penetration
  作者：Vinh L. Hoang、Yichao Zhang、Ryan J. Rafferty

  DOI：10.1016/j.tetlet.2017.09.071

  日期：2017.11

  Four new oxazoline based macrocycles have been constructed, said cycles were found to possess varying cytotoxicity against six different cancer cell lines: IC50 values of 6.4 mu M towards HeLa and 11.9 mu M towards LnCaP being the most potent. Two of the four macrocycles were found to have marginal cytotoxicity against MM.1S and MM.1R, myeloma cancer cell lines, and further evaluation showed that they also possessed rapid cellular uptake and accumulation characteristics. Through the structure-activity relationship comparisons between the four compounds, it was found that the C6 position of the E-ring is amendable to substitution and could possibly serve as a conjugation site for the development of a selective delivery system to MM.1R. (C) 2017 Elsevier Ltd. All rights reserved.