[(8R,11S,14R)-8-Hydroxymethyl-11-(3-isopropoxy-phenyl)-19-nitro-10,13-dioxo-2-oxa-9,12-diaza-tricyclo[14.2.2.1^3,7]henicosa-1(19),3,5,7(21),16(20),17-hexaen-14-yl]-carbamic acid tert-butyl ester | 173775-56-9

• 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: [(8R,11S,14R)-8-Hydroxymethyl-11-(3-isopropoxy-phenyl)-19-nitro-10,13-dioxo-2-oxa-9,12-diaza-tricyclo[14.2.2.1^3,7]henicosa-1(19),3,5,7(21),16(20),17-hexaen-14-yl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(8R,11S,14R)-8-(hydroxymethyl)-18-nitro-10,13-dioxo-11-(3-propan-2-yloxyphenyl)-2-oxa-9,12-diazatricyclo[14.2.2.13,7]henicosa-1(18),3,5,7(21),16,19-hexaen-14-yl]carbamate
• CAS: 173775-56-9
• 化学式: C₃₃H₃₈N₄O₉
• 分子量: 634.686
• InChiKey: ICAQIXYPYSPZED-ALTZYDRJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  46
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  181
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [(8R,11S,14R)-8-Hydroxymethyl-11-(3-isopropoxy-phenyl)-19-nitro-10,13-dioxo-2-oxa-9,12-diaza-tricyclo[14.2.2.1^3,7]henicosa-1(19),3,5,7(21),16(20),17-hexaen-14-yl]-carbamic acid tert-butyl ester 在 盐酸 、 二苯基磷酸 、 三氯化硼 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 2-(3-fluoro-4-nitrophenyl)-N-[(8R,11S,14R)-8-(hydroxymethyl)-11-(3-hydroxyphenyl)-18-nitro-10,13-dioxo-2-oxa-9,12-diazatricyclo[14.2.2.13,7]henicosa-1(18),3,5,7(21),16,19-hexaen-14-yl]acetamide
  参考文献：
  名称：

  Synthesis of Modified Carboxyl Binding Pockets of Vancomycin and Teicoplanin

  摘要：

  Sixteen-membered macrocycle 3 and 16+14 bicyclic compound 4, incorporating a terminal primary hydroxyl group in the peptide sequence, have been designed and synthesized. The syntheses feature the use of an efficient cycloetherification based on an intramolecular SNAr reaction for the formation of biaryl ether bonds. Cyclization of linear tetrapeptide 30, prepared via a convergent [2+2] segment coupling between 26 and 29, gave macrocycle 31 (P configuration) as a single isolable atropisomer. Removal of the Boc protecting group afforded the modified carboxyl binding pocket of vancomycin 3. A sequential 2-fold intramolecular SNAr reaction has been used to construct the model bicyclic system (i.e. 4) of the D-O-E-F-O-G ring of teicoplanin. Cyclization conditions (CsF, DMF, room temperature) are sufficiently mild that the configuration of the racemization-prone arylglycine residue was not affected. Chiral building blocks such as D-(1R)-[2-[(tert-butyldimethylsilyl)oxy] 1-[3-(allyloxy)phenyl]ethyl]amine 16, and L-(S)-N-Boc-[3-(isopropyloxy)phenyl]glycine (32) were synthesized employing Evans' asymmetric azidation method, while L-(S)-4-fluoro-3-nitrophenylalanine methyl ester 23 was prepared using Schollkopf's bislactim ether as chiral glycine template. Compound 3 showed interesting conformational properties compared to vancomycin and its binding with Ac-D-Ala was studied by NMR titration experiments. A dissociation constant (K-d = 5 x 10(-4)) was calculated by a curve fitting method. Compound 4 is currently the most advanced synthetic intermediate toward the total synthesis of teicoplanin.

  DOI：

  10.1021/jo961412m
• 作为产物：
  描述：

  D-N-BOC-4-fluoro-3-nitrophenylalanine 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 cesium fluoride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.67h， 生成 [(8R,11S,14R)-8-Hydroxymethyl-11-(3-isopropoxy-phenyl)-19-nitro-10,13-dioxo-2-oxa-9,12-diaza-tricyclo[14.2.2.1^3,7]henicosa-1(19),3,5,7(21),16(20),17-hexaen-14-yl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis of Modified Carboxyl Binding Pockets of Vancomycin and Teicoplanin

  摘要：

  Sixteen-membered macrocycle 3 and 16+14 bicyclic compound 4, incorporating a terminal primary hydroxyl group in the peptide sequence, have been designed and synthesized. The syntheses feature the use of an efficient cycloetherification based on an intramolecular SNAr reaction for the formation of biaryl ether bonds. Cyclization of linear tetrapeptide 30, prepared via a convergent [2+2] segment coupling between 26 and 29, gave macrocycle 31 (P configuration) as a single isolable atropisomer. Removal of the Boc protecting group afforded the modified carboxyl binding pocket of vancomycin 3. A sequential 2-fold intramolecular SNAr reaction has been used to construct the model bicyclic system (i.e. 4) of the D-O-E-F-O-G ring of teicoplanin. Cyclization conditions (CsF, DMF, room temperature) are sufficiently mild that the configuration of the racemization-prone arylglycine residue was not affected. Chiral building blocks such as D-(1R)-[2-[(tert-butyldimethylsilyl)oxy] 1-[3-(allyloxy)phenyl]ethyl]amine 16, and L-(S)-N-Boc-[3-(isopropyloxy)phenyl]glycine (32) were synthesized employing Evans' asymmetric azidation method, while L-(S)-4-fluoro-3-nitrophenylalanine methyl ester 23 was prepared using Schollkopf's bislactim ether as chiral glycine template. Compound 3 showed interesting conformational properties compared to vancomycin and its binding with Ac-D-Ala was studied by NMR titration experiments. A dissociation constant (K-d = 5 x 10(-4)) was calculated by a curve fitting method. Compound 4 is currently the most advanced synthetic intermediate toward the total synthesis of teicoplanin.

  DOI：

  10.1021/jo961412m

文献信息

• The first synthesis of a model bicyclic D-O-E-F-O-G ring of teicoplanin via sequential intramolecular SNAr reactions
  作者：Rene Beugelmans、Luc Neuville、Michele Bois-Choussy、Jieping Zhu

  DOI：10.1016/0040-4039(95)01876-j

  日期：1995.11

  A model bicyclic D-O-E-F-O-G ring (2) of teicoplanin (1) has been efficiently synthesized via sequential intramolecular SNAr reactions.