2,3,4-tri-O-acetylnarciclasine | 28526-38-7

• 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-tri-O-acetylnarciclasine
• 英文别名: Lycoricidinol-triacetat od. 1,2,3-Triacetoxy-8-hydroxy-6,7-methylendioxy-9-oxo-1,2,3,4,4a,9,10,10a-octahydro-10-aza-phenanthren；Narciclasin-2,3,4-triacetat；acetic acid 2,4-diacetoxy-7-hydroxy-6-oxo-2,3,4,4a,5,6-hexahydro[1,3]dioxolo[4,5-j]phenanthridin-3-yl ester；(4aR)-2t,3c,4c-triacetoxy-7-hydroxy-(4ar)-3,4,4a,5-tetrahydro-2H-[1,3]dioxolo[4,5-j]phenanthridin-6-one；2,3,4-(triacetoxy)-narciclasine；[(2S,3R,4S,4aR)-3,4-diacetyloxy-7-hydroxy-6-oxo-3,4,4a,5-tetrahydro-2H-[1,3]dioxolo[4,5-j]phenanthridin-2-yl] acetate
• CAS: 28526-38-7
• 化学式: C₂₀H₁₉NO₁₀
• 分子量: 433.372
• InChiKey: OCBMVGCBTMVZEP-LZBRWLDZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  147
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2,3,4-tri-O-acetylnarciclasine 在 四氧化锇 、 Hydroquinone 1,4-phthalazinediyl diether 、 偶氮二异丁腈 、 三正丁基氢锡 、 N-甲基吗啉氧化物 作用下， 以 水 、 N,N-二甲基甲酰胺 、 甲苯 、 丁酮 为溶剂， 反应 62.0h， 生成 [(1R,2S,3S,4S,4aR,11bS)-2,3-diacetyloxy-1,7-dihydroxy-6-oxo-2,3,4,4a,5,11b-hexahydro-1H-[1,3]dioxolo[4,5-j]phenanthridin-4-yl] acetate
  参考文献：
  名称：

  Antineoplastic Agents. 550. Synthesis of 10b(S)-Epipancratistatin from (+)-Narciclasine^,1

  摘要：

  By means of a five-step reaction sequence, narciclasine (2a), isolated from Narcissus sp., was converted to 10b(S)-epipancratistatin (3a) in 5.7% overall yield. The key step entailed a radical-initiated 10b,1 C-O cleavage employing tributyltin hydride to yield a B/C cis ring juncture (3b). Biological evaluation of 10b(S)-epipancratistatin (3a) provided evidence that antineoplastic activity was reduced by a factor of 10 when the B/C trans juncture was replaced with a B/C cis ring juncture.

  DOI：

  10.1021/np068046e
• 作为产物：
  描述：

  2,3,4,7-tetra-O-acetylnarciclasine 在 吡啶 、 水 作用下， 生成 2,3,4-tri-O-acetylnarciclasine
  参考文献：
  名称：

  Structure−Activity Relationship Analysis of Novel Derivatives of Narciclasine (an Amaryllidaceae Isocarbostyril Derivative) as Potential Anticancer Agents

  摘要：

  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.

  DOI：

  10.1021/jm8013585

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。
• 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。
• Mondon,A.; Krohn,K., Chemische Berichte, 1975, vol. 108, p. 445 - 463
  作者：Mondon,A.、Krohn,K.

  DOI：——

  日期：——
• Lycoricidinol and Lycoricidine, New Plant-growth Regulators in the Bulbs of Lycoris radiata HERB.
  作者：TOSHIHIKO OKAMOTO、YOSHIHIKO TORII、YO ISOGAI

  DOI：10.1248/cpb.16.1860

  日期：——
• 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.