2,3,4,7-tetra-O-acetylnarciclasine | 35596-02-2

• 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: 2,3,4,7-tetra-O-acetylnarciclasine
• 英文别名: narciclasine tetraacetate；(2S,3R,4S,4aR)-6-oxo-2,3,4,4a,5,6-hexahydro-[1,3]dioxolo[4,5-j]phenanthridine-2,3,4,7-tetrayl tetraacetate；narciclasine peracetate；Narciclasintetraacetat；(4aR)-2t,3c,4c,7-tetraacetoxy-(4ar)-3,4,4a,5-tetrahydro-2H-[1,3]dioxolo[4,5-j]phenanthridin-6-one；Lycoricidinol-tetraacetat od. 1,2,3,8-Tetraacetoxy-6,7-methylendioxy-9-oxo-1,2,3,4,4a,9,10,10a-octahydro-10-aza-phenanthren；2,3,4,7-O-tetraacetoxy-narciclasine；2,3,4,7-tetraacetoxynarciclasine；[(2S,3R,4S,4aR)-3,4,7-triacetyloxy-6-oxo-3,4,4a,5-tetrahydro-2H-[1,3]dioxolo[4,5-j]phenanthridin-2-yl] acetate
• CAS: 35596-02-2
• 化学式: C₂₂H₂₁NO₁₁
• 分子量: 475.409
• InChiKey: LFSZASRPEMYAPR-RWCSOYMTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  153
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  2,3,4,7-tetra-O-acetylnarciclasine 在 甲醇 、 palladium 10% on activated carbon 、 氢气 、 sodium methylate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 23.0 ℃ 、101.33 kPa 条件下， 反应 4.0h， 生成 cis-1,10b-Dihydronarciclasin
  参考文献：
  名称：

  Human Cytochrome P450 Liability Studies of trans-Dihydronarciclasine: A Readily Available, Potent, and Selective Cancer Cell Growth Inhibitor

  摘要：

  The cytochrome P450 activities of the naturally occurring Amaryllidaceae alkaloid narciclasine (3), isolated from Narcissus pseudonarcissus, and synthetic derivative trans-dihydronarciclasine (5) are reported. While narciclasine was found to possess potent inhibitory activity to human CYP3A4, its dihydro analogue was inactive. This study revealed that the C1-C10b double bond is required for inhibition of this crucial metabolizing enzyme. Compound 5 also demonstrated no inhibition of the related human cytochromes CYP19 and CYPIA1. This study elevates the status of trans-dihydronarciclasine (5) as a highly privileged, readily available molecule, with potent and selective anticancer activity.

  DOI：

  10.1021/np100657w
• 作为产物：
  描述：

  乙酸酐 、 水仙环素 在 4-二甲氨基吡啶 、 三乙胺 作用下， 反应 4.0h， 以64%的产率得到2,3,4,7-tetra-O-acetylnarciclasine
  参考文献：
  名称：

  天然水仙环素转化为其 C-1 和 C-6 衍生物及其抗肿瘤活性评价：水仙环素的一些不寻常的化学性质

  摘要：

  在寻找合成水仙环素 C-1 类似物的通用、有效途径的过程中，天然水仙环素受到保护，并使用一种新的半合成途径转化为其 C-1 烯醇衍生物。为了在 C-1 处进行交叉偶联，尝试将该材料转化为其三氟甲磺酸酯，结果在 C-6 处产生了三氟甲磺酸酯，并成功与多种功能偶联。四种新型化合物经过七个步骤后完全脱保护，并评估其针对三种癌细胞系的细胞毒活性。与水仙环素相比，只有一种衍生物表现出中等活性。提供所有新化合物的光谱和物理数据。

  DOI：

  10.3390/molecules27134141

文献信息

• ISOCARBOSTYRIL ALKALOID DERIVATIVES HAVING ANTI-PROLIFERATIVE AND ANTI-MIGRATORY ACTIVITIES
  申请人：Ingrassia Laurent

  公开号：US20100076005A1

  公开（公告）日：2010-03-25

  Isocarbostyril alkaloid derivatives having an anti-proliferative and anti-migratory activities are disclosed. In particular, compounds of formula (I) or (II), as well as stereoisomers, tautomers, racemates, prodrugs, metabolites thereof, pharmaceutically acceptable salt and/or solvate are encompassed which are useful in the treatment and prophylaxis of cancer. Methods of preparation are also disclosed.

  揭示了具有抗增殖和抗迁移活性的异喹啉生物碱衍生物。具体来说，公开了符合以下化学式(I)或(II)的化合物，以及其立体异构体、互变异构体、消旋体、前药、代谢物、药学上可接受的盐和/或溶剂，这些化合物在癌症的治疗和预防中很有用。还公开了制备方法。
• Synthesis of 10b-R-hydroxy-pancratistatin via narciclasine
  作者：George R. Pettit、Noeleen Melody、Michael O'Sullivan、Michael A. Thompson、Delbert L. Herald、Brian Coates

  DOI：10.1039/c39940002725

  日期：——

  A diastereoselective synthesis of 10b-R-hydroxy-pancratistatin 3 from narciclasine 1 has been achieved.

  从 narciclasine 1 中实现了 10b-R-hydroxy-pancratistatin 3 的非对映选择性合成。
• [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）。
• Circularly polarized luminescence of natural products lycorine and narciclasine: role of excited-state intramolecular proton-transfer and test of pH sensitivity
  作者：Giuseppe Mazzeo、Marco Fusè、Antonio Evidente、Sergio Abbate、Giovanna Longhi

  DOI：10.1039/d3cp02600k

  日期：——

  studied. So far natural compounds have not been investigated much. We fill the gap here by measuring circular dichroism (CD) and CPL of lycorine and narciclasine, the most abundant known alkaloid and isocarbostyril from Amaryllidaceae, which exhibit a large spectrum of biological activities and are promising anticancer compounds. Dual fluorescence detection in narciclasine led us to unveil an occurring

  圆偏振发光（CPL）越来越受到人们的关注，不仅因为它的应用潜力，而且因为它提供了对手性分子激发态特性的理解。然而，CPL的应用主要在材料科学领域：特殊有机分子和聚合物、金属（镧系元素）络合物和有机染料正在积极而深入地研究。迄今为止，对天然化合物的研究还不多。我们通过测量石蒜碱和水仙花碱的圆二色性 (CD) 和 CPL 填补了这一空白，石蒜碱和水仙花碱是石蒜科中最丰富的已知生物碱和异喹诺酮，具有广泛的生物活性，是有前途的抗癌化合物。水仙环素的双荧光检测使我们揭示了发生的激发态分子内质子转移 (ESIPT) 过程，该机制很好地解释了水仙环素中观察到的斯托克斯位移和 CPL 光谱。同样的分子也可以用作 pH 手性光学开关。在吸收和发射方面，石蒜碱和水仙环素也通过密度泛函理论 (DFT) 计算进行了计算研究，进一步揭示了它们的特性。
• Structure−Activity Relationship Analysis of Novel Derivatives of Narciclasine (an <i>Amaryllidaceae</i> Isocarbostyril Derivative) as Potential Anticancer Agents
  作者：Laurent Ingrassia、Florence Lefranc、Janique Dewelle、Laurent Pottier、Véronique Mathieu、Sabine Spiegl-Kreinecker、Sébastien Sauvage、Mohamed El Yazidi、Mischaël Dehoux、Walter Berger、Eric Van Quaquebeke、Robert Kiss

  DOI：10.1021/jm8013585

  日期：2009.2.26

  Narciclasine (1) is a plant growth regulator that has been previously demonstrated to be proapoptotic to cancer cells at high concentrations (>= 1 mu M). Data generated in the present study show that narciclasine displays potent antitumor effects in apoptosis-resistant as well as in apoptosis-sensitive cancer cells by impairing the organization of the actin cytoskeleton in cancer cells at concentrations that are not cytotoxic (IC50 values of 30-90 nM). The current study further revealed that any chemical modification to the narciclasine backbone generally led to compounds of variable stability, weaker activity, or even the complete loss of antiproliferative effects in vitro. However, one hemisynthetic derivative of narciclasine, compound 7k, demonstrated by both the intravenous and oral routes higher in vivo antitumor activity in human orthotopic 4, glioma models in mice when compared to narciclasine at nontoxic doses. Narciclasine and compound 7k may therefore be of potential use to combat brain tumors.