(2S,3S,4S,5R,6R)-6-[[(3S,4S,4aR,6aR,6bS,8R,8aR,12aS,14aR,14bR)-8a-[(2S,3R,4S,5R,6S)-5-(6-aminohexanoylamino)-3-[(2S,3R,4S,5R,6S)-3,4-dihydroxy-6-methyl-5-[(2S,3R,4S,5R)-3,4,5-trihydroxyoxan-2-yl]oxyoxan-2-yl]oxy-4-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxycarbonyl-4-formyl-8-hydroxy-4,6a,6b,11,11,14b-hexamethyl-1,2,3,4a,5,6,7,8,9,10,12,12a,14,14a-tetradecahydropicen-3-yl]oxy]-3-hydroxy-5-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4-[(2S,3R,4S,5R)-3,4,5-trihydroxyoxan-2-yl]oxyoxane-2-carboxylic acid | 1392506-81-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (2S,3S,4S,5R,6R)-6-[[(3S,4S,4aR,6aR,6bS,8R,8aR,12aS,14aR,14bR)-8a-[(2S,3R,4S,5R,6S)-5-(6-aminohexanoylamino)-3-[(2S,3R,4S,5R,6S)-3,4-dihydroxy-6-methyl-5-[(2S,3R,4S,5R)-3,4,5-trihydroxyoxan-2-yl]oxyoxan-2-yl]oxy-4-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxycarbonyl-4-formyl-8-hydroxy-4,6a,6b,11,11,14b-hexamethyl-1,2,3,4a,5,6,7,8,9,10,12,12a,14,14a-tetradecahydropicen-3-yl]oxy]-3-hydroxy-5-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4-[(2S,3R,4S,5R)-3,4,5-trihydroxyoxan-2-yl]oxyoxane-2-carboxylic acid
• CAS: 1392506-81-8
• 化学式: C₇₀H₁₁₂N₂O₃₃
• 分子量: 1509.65
• InChiKey: DJCQFLVEMKAKCE-GICCTTDKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.6
• 重原子数：
  105
• 可旋转键数：
  23
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  561
• 氢给体数：
  19
• 氢受体数：
  34

反应信息

• 作为反应物：
  描述：

  (2S,3S,4S,5R,6R)-6-[[(3S,4S,4aR,6aR,6bS,8R,8aR,12aS,14aR,14bR)-8a-[(2S,3R,4S,5R,6S)-5-(6-aminohexanoylamino)-3-[(2S,3R,4S,5R,6S)-3,4-dihydroxy-6-methyl-5-[(2S,3R,4S,5R)-3,4,5-trihydroxyoxan-2-yl]oxyoxan-2-yl]oxy-4-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxycarbonyl-4-formyl-8-hydroxy-4,6a,6b,11,11,14b-hexamethyl-1,2,3,4a,5,6,7,8,9,10,12,12a,14,14a-tetradecahydropicen-3-yl]oxy]-3-hydroxy-5-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4-[(2S,3R,4S,5R)-3,4,5-trihydroxyoxan-2-yl]oxyoxane-2-carboxylic acid 、 CB-Gly-OH, tetratriethylammonium salt 在 三乙胺 、 3-(二乙氧基邻酰氧基)-1,2,3-苯并三嗪-4-酮 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.5h， 以36%的产率得到
  参考文献：
  名称：

  QS-21 变体的合成和临床前评估导致简化的疫苗佐剂和机械探针

  摘要：

  QS-21 是一种有效的免疫刺激皂苷，目前正在临床研究中作为各种疫苗的佐剂，以治疗传染病、癌症和认知障碍。在此，我们报告了简化 QS-21 同源物的设计、合成和临床前评估，以定义对佐剂活性至关重要的关键结构特征。线性四糖结构域的截断表明，三糖变体与 QS-21 等效，而相应的二糖和单糖同源物分别具有更强的毒性和更弱的效力。三糖系列中酰基链结构域的修饰表明末端羧酸具有良好的耐受性，而末端胺导致佐剂活性降低。在某些情况下，末端胺的酰化可以 恢复佐剂活性并能够合成荧光标记的 QS-21 变体。用这些探针进行的细胞研究表明，与传统观点相反，这些荧光标记皂苷中最高的佐剂活性不只是与质膜结合，而是被树突细胞内化。

  DOI：

  10.1021/ja305121q
• 作为产物：
  描述：

  在 palladium 10% on activated carbon 、 氢气 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 21.0 ℃ 、344.75 kPa 条件下， 反应 27.0h， 以78%的产率得到(2S,3S,4S,5R,6R)-6-[[(3S,4S,4aR,6aR,6bS,8R,8aR,12aS,14aR,14bR)-8a-[(2S,3R,4S,5R,6S)-5-(6-aminohexanoylamino)-3-[(2S,3R,4S,5R,6S)-3,4-dihydroxy-6-methyl-5-[(2S,3R,4S,5R)-3,4,5-trihydroxyoxan-2-yl]oxyoxan-2-yl]oxy-4-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxycarbonyl-4-formyl-8-hydroxy-4,6a,6b,11,11,14b-hexamethyl-1,2,3,4a,5,6,7,8,9,10,12,12a,14,14a-tetradecahydropicen-3-yl]oxy]-3-hydroxy-5-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4-[(2S,3R,4S,5R)-3,4,5-trihydroxyoxan-2-yl]oxyoxane-2-carboxylic acid
  参考文献：
  名称：

  QS-21 变体的合成和临床前评估导致简化的疫苗佐剂和机械探针

  摘要：

  QS-21 是一种有效的免疫刺激皂苷，目前正在临床研究中作为各种疫苗的佐剂，以治疗传染病、癌症和认知障碍。在此，我们报告了简化 QS-21 同源物的设计、合成和临床前评估，以定义对佐剂活性至关重要的关键结构特征。线性四糖结构域的截断表明，三糖变体与 QS-21 等效，而相应的二糖和单糖同源物分别具有更强的毒性和更弱的效力。三糖系列中酰基链结构域的修饰表明末端羧酸具有良好的耐受性，而末端胺导致佐剂活性降低。在某些情况下，末端胺的酰化可以 恢复佐剂活性并能够合成荧光标记的 QS-21 变体。用这些探针进行的细胞研究表明，与传统观点相反，这些荧光标记皂苷中最高的佐剂活性不只是与质膜结合，而是被树突细胞内化。

  DOI：

  10.1021/ja305121q

文献信息

• [EN] MINIMAL SAPONIN ANALOGUES, SYNTHESIS AND USE THEREOF<br/>[FR] ANALOGUES DE SAPONINE À STRUCTURE MINIMALE, SYNTHÈSE ET UTILISATION
  申请人：SLOAN KETTERING INST CANCER

  公开号：WO2015184451A1

  公开（公告）日：2015-12-03

  Truncated triterpene saponin analogues containing a trisaccharide or tetrasaccharide ester are disclosed. Also disclosed are pharmaceutical compositions comprising truncated saponin analogues and synthetic methods of producing the truncated saponin analogues. Another aspect of the present application relates to a method for immunizing a subject, comprising administering to the subject the pharmaceutical composition comprising a minimal saponin analogue and an antigen.

  披露了含有三糖或四糖酯的截短三萜皂苷类似物。还披露了包含截短皂苷类似物的药物组合物以及生产截短皂苷类似物的合成方法。本申请的另一个方面涉及一种免疫主体的方法，包括向主体施用包含最小皂苷类似物和抗原的药物组合物。
• Design, synthesis, and immunologic evaluation of vaccine adjuvant conjugates based on QS-21 and tucaresol
  作者：Alberto Fernández-Tejada、Eric K. Chea、Constantine George、Jeffrey R. Gardner、Philip O. Livingston、Govind Ragupathi、Derek S. Tan、David Y. Gin

  DOI：10.1016/j.bmc.2014.09.016

  日期：2014.11

  Immunoadjuvants are used to potentiate the activity of modern subunit vaccines that are based on molecular antigens. An emerging approach involves the combination of multiple adjuvants in a single formulation to achieve optimal vaccine efficacy. Herein, to investigate such potential synergies, we synthesized novel adjuvant conjugates based on the saponin natural product QS-21 and the aldehyde tucaresol via chemoselective acylation of an amine at the terminus of the acyl chain domain in QS saponin variants. In a preclinical mouse vaccination model, these QS saponin-tucaresol conjugates induced antibody responses similar to or slightly higher than those generated with related QS saponin variants lacking the tucaresol motif. The conjugates retained potent adjuvant activity, low toxicity, and improved activity-toxicity profiles relative to QS-21 itself and induced IgG subclass profiles similar to those of QS-21, indicative of both Th1 cellular and Th2 humoral immune responses. This study opens the door to installation of other substituents at the terminus of the acyl chain domain to develop additional QS saponin conjugates with desirable immunologic properties. (C) 2014 Elsevier Ltd. All rights reserved.