2-tert-butyldimethylsilyloxy-3,4-acetonide-7-deoxynarciclasine | 876049-96-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 2-tert-butyldimethylsilyloxy-3,4-acetonide-7-deoxynarciclasine
• 英文别名: 2-[tert-butyldimethylsilyl]oxy-3,4-isopropylidene-7-deoxynarciclasine；2-[tert-butyl-1,1-dimethyIsilyI]-oxy-3,4-isopropylidene-7-deoxy-narciclasine；(13R,14S,18S,19S)-19-[tert-butyl(dimethyl)silyl]oxy-16,16-dimethyl-5,7,15,17-tetraoxa-12-azapentacyclo[11.7.0.02,10.04,8.014,18]icosa-1(20),2,4(8),9-tetraen-11-one
• CAS: 876049-96-6
• 化学式: C₂₃H₃₁NO₆Si
• 分子量: 445.588
• InChiKey: XAHDDMCNCIYOSB-NMLBUPMWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.83
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  75.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-tert-butyldimethylsilyloxy-3,4-acetonide-7-deoxynarciclasine 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 48.0h， 以89%的产率得到2-tert-butyldimethylsilyloxy-3,4-acetonide-5-aza-6-deoxynarciclasine
  参考文献：
  名称：

  7-脱氧水杨酸和7-脱氧-反式-二氢水杨酸的分离和结构修饰。

  摘要：

  作为潘克拉斯汀（1）构效关系研究的扩展，首先对各种技术进行了评估，以分离分离自Hymenocallis littoralis的7-脱氧水杨酸（2b）和7-脱氧水-二氢水杨酸（3a）的混合物。然后，用于否则难于分离的有效解决方案允许使用氢化铝锂还原被保护的（4c和5c）醇2b和3a的内酰胺羰基。甲硅烷基酯/丙酮化物保护的6a的裂解（TBAF，然后是H2SO4）给出了胺8。使用X射线晶体结构测定来确定3,4-丙酮化物-5-氮杂-6-脱氧水杨酸（6b），5的结构。 -氮杂-6-脱氧水杨酸（8a）和5-氮杂-6-脱氧-反式二氢水杨酸（9a，9b）。针对鼠类P388淋巴细胞白血病和一系列人类癌细胞系，通常发现母体天然产物7-脱氧水杨酸（2b）和7-脱氧-反式二氢水杨酸（3a）比具有这种结构修饰的化合物对癌细胞的生长具有更大的抑制作用（GI50 0.1至<0.01 microg / mL）。作为胺8的

  DOI：

  10.1021/np058068l
• 作为产物：
  描述：

  2alpha,3beta,4beta-三羟基-2,3,4,4abeta,5,6-六氢[1,3]二氧杂环戊并[4,5-j]菲啶-6-酮 在 sodium hydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 2-tert-butyldimethylsilyloxy-3,4-acetonide-7-deoxynarciclasine
  参考文献：
  名称：

  Evaluation of anti-HCV activity and SAR study of (+)-lycoricidine through targeting of host heat-stress cognate 70 (Hsc70)

  摘要：

  The anti hepatitis C virus (HCV) activity of (+)-lycoricidine (1) was evaluated for the first time in this letter, yielding an EC50 value of 0.55 nmol/mL and an selection index (SI) value of 12.72. Further studies indicated that 1 induced this effect by down-regulating host heat-stress cognate 70 (Hsc70) expression. In addition, 20 derivatives were designed and synthesised to investigate the basic structure-activity relationship (SAR) of the title compound. Several of these derivatives exhibit a good inhibition of HCV, such as compound 3 (EC50 = 0.68 nmol/mL, SI = 33.86), compound 2d (EC50 = 15 nmol/mL, SI = 12) and compound 5 (EC50 = 33 nmol/mL, SI > 10.91). Meanwhile, the experimental data suggest that the modification of certain groups of (+)-lycoricidine can reduce the cytotoxicity of the compounds. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.089

文献信息

• [EN] SYNTHESIS OF SODIUM NARCISTATIN AND RELATED COMPOUNDS<br/>[FR] SYNTHESE DE NARCISTATINE DE SODIUM ET COMPOSES ASSOCIES
  申请人：STATE OF ARIZONA ACTING FOR AN

  公开号：WO2006076726A1

  公开（公告）日：2006-07-20

  (EN) The present invention involves use of the compounds narciclasine (2a) and 7-deoxy-narciclasine (2c), which are obtained via isolation from the medicinal plant species Narcissus (Amaryllidaceae), as precursors in a novel synthesis method in which each of these compounds are selectively hydrogenated to produce trans-dihydronarciclasine (1a) and 7-deoxy-trans-dihydronarciclasine (1c). Also described herein is a novel synthesis method for producing sodium narcistatin (11) from narciclasine (2a). Further described herein are certain novel 3,4-cyclic phosphate prodrugs, including sodium-7-deoxynarcistatin (8), sodium-7-deoxy-transdihydronarcistatin (9), and sodium transdihydronarcistatin (10).(FR) L'invention concerne l'utilisation de composés narciclasine (2a) et 7-déoxy-narciclasine (2c), obtenus par isolation à partir de l'espèce végétale médicinale Narcissus (Amaryllidaceae), en tant que précurseurs dans un nouveau procédé de synthèse dans lequel chacun de ces composés est sélectivement hydrogéné afin que soient produites de la trans-dihydronarciclasine (1a) et de la 7-déoxy-trans-dihydronarciclasine (1c). L'invention concerne également un nouveau procédé de synthèse pour la production de narcistatine de sodium (11) à partir de narciclasine (2a). L'invention concerne en outre certains nouveaux promédicaments de phosphate 3,4 cyclique, à savoir : sodium-7-déoxynarcistatine (8), sodium-7-déoxy-transdihydronarcistatine (9), et sodium transdihydronarcistatine (10).

  本发明涉及使用从医用植物品种水仙属（石蒜科）中分离得到的化合物narciclasine（2a）和7-去氧-narciclasine（2c）作为前体，进行新型合成方法，其中每个化合物都被选择性氢化以产生trans-dihydronarciclasine（1a）和7-去氧-trans-dihydronarciclasine（1c）。本文还描述了一种从narciclasine（2a）制备钠narcistatin（11）的新型合成方法。此外，本文还描述了某些新型3,4-环磷酸酯前药，包括：sodium-7-deoxynarcistatin（8）、sodium-7-deoxy-transdihydronarcistatin（9）和sodium transdihydronarcistatin（10）。
• Antineoplastic Agents. 454. Synthesis of the Strong Cancer Cell Growth Inhibitors <i>trans</i>-Dihydronarciclasine and 7-Deoxy-<i>trans</i>-dihydronarciclasine
  作者：George R. Pettit、Sylvie Ducki、Stephen A. Eastham、Noeleen Melody

  DOI：10.1021/np9001948

  日期：2009.7.24

  To further pursue the antineoplastic leads offered by Our isolation of trans-dihydronarciclasine (1a) and 7-deoxy-trans-dihydronarciclasine (1c) from two medicinal plant species of the Amaryllidaceae family, a practical palladium-catalyzed hydrogenation procedure was developed for the synthesis of these isocarbostyrils from narciclasine (2a) and 7-deoxynarciclasine (2c).
• Isolation and Structural Modification of 7-Deoxynarciclasine and 7-Deoxy-<i>trans</i>-Dihydronarciclasine^,1
  作者：George R. Pettit、Stephen A. Eastham、Noeleen Melody、Brian Orr、Delbert L. Herald、Jane McGregor、John C. Knight、Dennis L. Doubek、George R. Pettit、Lynnette C. Garner、Joy A. Bell

  DOI：10.1021/np058068l

  日期：2006.1.1

  relationship studies of pancratistatin (1), various techniques were first evaluated for separating the mixtures of 7-deoxynarciclasine (2b) and 7-deoxy-trans-dihydronarciclasine (3a) isolated from Hymenocallis littoralis. An efficient solution for that otherwise difficult separation then allowed the lactam carbonyl group of protected (4c and 5c) alcohols 2b and 3a to be reduced employing lithium aluminum hydride

  作为潘克拉斯汀（1）构效关系研究的扩展，首先对各种技术进行了评估，以分离分离自Hymenocallis littoralis的7-脱氧水杨酸（2b）和7-脱氧水-二氢水杨酸（3a）的混合物。然后，用于否则难于分离的有效解决方案允许使用氢化铝锂还原被保护的（4c和5c）醇2b和3a的内酰胺羰基。甲硅烷基酯/丙酮化物保护的6a的裂解（TBAF，然后是H2SO4）给出了胺8。使用X射线晶体结构测定来确定3,4-丙酮化物-5-氮杂-6-脱氧水杨酸（6b），5的结构。 -氮杂-6-脱氧水杨酸（8a）和5-氮杂-6-脱氧-反式二氢水杨酸（9a，9b）。针对鼠类P388淋巴细胞白血病和一系列人类癌细胞系，通常发现母体天然产物7-脱氧水杨酸（2b）和7-脱氧-反式二氢水杨酸（3a）比具有这种结构修饰的化合物对癌细胞的生长具有更大的抑制作用（GI50 0.1至<0.01 microg / mL）。作为胺8的
• Evaluation of anti-HCV activity and SAR study of (+)-lycoricidine through targeting of host heat-stress cognate 70 (Hsc70)
  作者：Duo-Zhi Chen、Jian-Dong Jiang、Ke-Qing Zhang、Hong-Ping He、Ying-Tong Di、Yu Zhang、Jie-Yun Cai、Lei Wang、Shun-Lin Li、Ping Yi、Zong-Gen Peng、Xiao-Jiang Hao

  DOI：10.1016/j.bmcl.2013.02.089

  日期：2013.5

  The anti hepatitis C virus (HCV) activity of (+)-lycoricidine (1) was evaluated for the first time in this letter, yielding an EC50 value of 0.55 nmol/mL and an selection index (SI) value of 12.72. Further studies indicated that 1 induced this effect by down-regulating host heat-stress cognate 70 (Hsc70) expression. In addition, 20 derivatives were designed and synthesised to investigate the basic structure-activity relationship (SAR) of the title compound. Several of these derivatives exhibit a good inhibition of HCV, such as compound 3 (EC50 = 0.68 nmol/mL, SI = 33.86), compound 2d (EC50 = 15 nmol/mL, SI = 12) and compound 5 (EC50 = 33 nmol/mL, SI > 10.91). Meanwhile, the experimental data suggest that the modification of certain groups of (+)-lycoricidine can reduce the cytotoxicity of the compounds. (C) 2013 Elsevier Ltd. All rights reserved.