(N-(3-benzyloxypyridyl-2-carbonyl)-D-Ser-Pip-Gly-Sar-NMe-Val)2 (serine hydroxyl) dilactone | 203807-29-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (N-(3-benzyloxypyridyl-2-carbonyl)-D-Ser-Pip-Gly-Sar-NMe-Val)2 (serine hydroxyl) dilactone
• 英文别名: 3-phenylmethoxy-N-[(3R,7S,16S,23R,27S,36S)-8,11,28,31-tetramethyl-2,6,9,12,15,22,26,29,32,35-decaoxo-23-[(3-phenylmethoxypyridine-2-carbonyl)amino]-7,27-di(propan-2-yl)-5,25-dioxa-1,8,11,14,21,28,31,34-octazatricyclo[34.4.0.016,21]tetracontan-3-yl]pyridine-2-carboxamide
• CAS: 203807-29-8
• 化学式: C₆₆H₈₄N₁₂O₁₆
• 分子量: 1301.46
• InChiKey: UYJBTHYHSIYUTH-PXENPBASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  94
• 可旋转键数：
  12
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  335
• 氢给体数：
  4
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  (N-(3-benzyloxypyridyl-2-carbonyl)-D-Ser-Pip-Gly-Sar-NMe-Val)2 (serine hydroxyl) dilactone 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 以94%的产率得到(N-(3-hydroxypyridyl-2-carbonyl)-D-Ser-Pip-Gly-Sar-NMe-Val)2 (serine hydroxyl) dilactone
  参考文献：
  名称：

  Synthesis of key sandramycin analogs: systematic examination of the intercalation chromophore

  摘要：

  The preparation and examination of 2-22 constituting a systematic study of the chromophore of sandramycin (1) are detailed. Fluorescence quenching studies were used to establish binding constants for 1-24 within calf thymus DNA, within a single high affinity bis-intercalation binding site 5'-d(GCATGC)(2), and to establish the preference for sandramycin binding to 5'-d(GCXXGC)(2) where XX = AT, TA, GC, and CG. From the latter studies, sandramycin was found to exhibit a preference that follows the order: 5'-d(GCATGC)(2) > 5'-d(GCGCGC)(2), Delta Delta G degrees = 0.3 kcal/mol > 5'-d(GCTAGC)(2), 5'-d(GCCGGC)(2), Delta Delta G degrees = 0.6 kcal/mol although it binds with high affinity to all four deoxyoligonucleotides. The two highest affinity sequences constitute repeating 5'-PuPy motifs with each intercalation event occurring at a 5'-PyPu step. The most effective sequence constitutes the less stable duplex, contains the sterically most accessible minor groove central to the bis-intercalation site, and the ability to accept two gly-NH/T C2 carbonyl H-bonds identified in prior NMR studies. Similarly, the contribution of the individual structural features of the chromophore were assessed with the high affinity duplex sequence 5'-d(GCATGC)(2). To a first approximation, the cytotoxic properties were found to parallel trends established in the DNA binding affinities. The exception to this generalization was 4 which lacks the sandramycin chromophore phenol. Although typically 4-10x less potent than sandramycin against leukemia cell lines, it proved to be 1-10,000x more potent against melanomas, carcinomas, and adenocarcinomas exhibiting IC50 values of IpM-10 nM placing it among the most potent agents identified to date. Additionally, the first disclosure of the HIV-1 reverse transcriptase inhibitory activity of sandramycin (1) as well as that of its key analogs are described and define the chromophore structural features required for their exceptional potency. Two analogs, 18 and 3, roughly maintain the HIV-I reverse transcriptase inhibitory potency of 1 but exhibit substantially diminished cytotoxic activity (10(2) - 10(3)x). (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(97)10014-1
• 作为产物：
  描述：

  3-苄氧基吡啶-2-羧酸苄基酯 在 lithium hydroxide 、 碳酸氢钠 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 (N-(3-benzyloxypyridyl-2-carbonyl)-D-Ser-Pip-Gly-Sar-NMe-Val)2 (serine hydroxyl) dilactone
  参考文献：
  名称：

  Synthesis of key sandramycin analogs: systematic examination of the intercalation chromophore

  摘要：

  The preparation and examination of 2-22 constituting a systematic study of the chromophore of sandramycin (1) are detailed. Fluorescence quenching studies were used to establish binding constants for 1-24 within calf thymus DNA, within a single high affinity bis-intercalation binding site 5'-d(GCATGC)(2), and to establish the preference for sandramycin binding to 5'-d(GCXXGC)(2) where XX = AT, TA, GC, and CG. From the latter studies, sandramycin was found to exhibit a preference that follows the order: 5'-d(GCATGC)(2) > 5'-d(GCGCGC)(2), Delta Delta G degrees = 0.3 kcal/mol > 5'-d(GCTAGC)(2), 5'-d(GCCGGC)(2), Delta Delta G degrees = 0.6 kcal/mol although it binds with high affinity to all four deoxyoligonucleotides. The two highest affinity sequences constitute repeating 5'-PuPy motifs with each intercalation event occurring at a 5'-PyPu step. The most effective sequence constitutes the less stable duplex, contains the sterically most accessible minor groove central to the bis-intercalation site, and the ability to accept two gly-NH/T C2 carbonyl H-bonds identified in prior NMR studies. Similarly, the contribution of the individual structural features of the chromophore were assessed with the high affinity duplex sequence 5'-d(GCATGC)(2). To a first approximation, the cytotoxic properties were found to parallel trends established in the DNA binding affinities. The exception to this generalization was 4 which lacks the sandramycin chromophore phenol. Although typically 4-10x less potent than sandramycin against leukemia cell lines, it proved to be 1-10,000x more potent against melanomas, carcinomas, and adenocarcinomas exhibiting IC50 values of IpM-10 nM placing it among the most potent agents identified to date. Additionally, the first disclosure of the HIV-1 reverse transcriptase inhibitory activity of sandramycin (1) as well as that of its key analogs are described and define the chromophore structural features required for their exceptional potency. Two analogs, 18 and 3, roughly maintain the HIV-I reverse transcriptase inhibitory potency of 1 but exhibit substantially diminished cytotoxic activity (10(2) - 10(3)x). (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(97)10014-1