cyclo-[Orn(Nα-6-octyloxy-2-naphthoyl)-Thr-Pro-hTyr-Orn(Nδ-Cbz)-Pro(4S-N3)] | 1203556-95-9

• 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: cyclo-[Orn(Nα-6-octyloxy-2-naphthoyl)-Thr-Pro-hTyr-Orn(Nδ-Cbz)-Pro(4S-N3)]
• CAS: 1203556-95-9
• 化学式: C₆₁H₇₉N₁₁O₁₂
• 分子量: 1158.36
• InChiKey: QLSSYDJKKQGVPG-QZFJDLAHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.74
• 重原子数：
  84.0
• 可旋转键数：
  21.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  322.9
• 氢给体数：
  8.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  cyclo-[Orn(Nα-6-octyloxy-2-naphthoyl)-Thr-Pro-hTyr-Orn(Nδ-Cbz)-Pro(4S-N3)] 、 对甲苯磺酸 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以93%的产率得到N-[(3S,6S,9S,15S,18S,24S,26S)-26-amino-3-(3-aminopropyl)-15-[(1R)-1-hydroxyethyl]-6-[2-(4-hydroxyphenyl)ethyl]-2,5,8,14,17,23-hexaoxo-1,4,7,13,16,22-hexazatricyclo[22.3.0.09,13]heptacosan-18-yl]-6-octoxynaphthalene-2-carboxamide;4-methylbenzenesulfonic acid
  参考文献：
  名称：

  Total synthesis and structure–activity relationships of caspofungin-like macrocyclic antifungal lipopeptides

  摘要：

  The echinocandins represent a well-known class of macrocyclic antifungal lipopeptides that can be used for treatment of invasive fungal infections. Due to their complex chemical structures and synthetic difficulties, the structure activity relationships (SARs) of them are still limited. A total synthetic approach was developed to synthesize structurally diverse caspofungin-like antifungal cyclic lipopeptides, allowing for systemically investigating their SARs. Most of the designed cyclic lipopeptides showed potent antifungal activities with broad spectrum. In particular, several compounds (e.g., 30a, 30e-h, 31a-d, 32c, and 33a,b) were more active in vitro against Candida albicans or Aspergillus fumigatus than caspofungin. The findings in this work indicated that the 'left' tripeptide segment of cyclic lipopeptide scaffold might be suitable for a hydrophilic structural motif, whereas the 'right' lipotripeptide segment was preferred as a hydrophobic core. The alkoxy-naphthoyl was found to be optimal side chain and alkyl length could affect the SARs of alkoxy-aroyl side chains. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2012.02.015
• 作为产物：
  描述：

  Nα-Boc-Orn(Nδ-Cbz)-Pro(4S-N3)-OMe 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 108.34h， 生成 cyclo-[Orn(Nα-6-octyloxy-2-naphthoyl)-Thr-Pro-hTyr-Orn(Nδ-Cbz)-Pro(4S-N3)]
  参考文献：
  名称：

  Total synthesis and structure–activity relationships of new echinocandin-like antifungal cyclolipohexapeptides

  摘要：

  A series of new echinocandin-like cyclolipohexapeptides were designed and total synthesized via solution phase [3 + 3]-segment coupling strategy with an attempt to improve antifungal activity. The designed compounds showed potent antifungal activities with broad spectrum. In particular, 11 compounds (i.e. 28a-e, 28g, 28i-j, 29a, 29c and 29e) showed better in vitro antifungal activities against Candida albicans or Aspergillus fumigatus than caspofungin. Moreover, the synthesized compounds provided new SAR information for the echinocandins. The findings in this work suggested that the "left" tripeptide segment of cyclolipohexapeptide scaffold might be a hydrophilic structural motif, whereas the "right" lipopeptide segment was preferred as a hydrophobic core. The amino acid component of the cyclolipohexapeptide scaffold could significantly affect the SAR of the side chains. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.01.054