cis-1,10b-Dihydronarciclasin-tetraacetat | 40042-06-6

• 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: cis-1,10b-Dihydronarciclasin-tetraacetat
• 英文别名: 2,3,4,7-tetraacetoxy-cis-dihydronarciclasine；(4aR)-2t,3c,4c,7-tetraacetoxy-(4ar,11bc)-1,3,4,4a,5,11b-hexahydro-2H-[1,3]dioxolo[4,5-j]phenanthridin-6-one；2,3,4,7-O-tetraacetoxy-cis-dihydronarciclasine；[(2S,3R,4S,4aR,11bS)-3,4,7-triacetyloxy-6-oxo-2,3,4,4a,5,11b-hexahydro-1H-[1,3]dioxolo[4,5-j]phenanthridin-2-yl] acetate
• CAS: 40042-06-6
• 化学式: C₂₂H₂₃NO₁₁
• 分子量: 477.425
• InChiKey: KFEHMJDKBKJHRD-SSXBFIPSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  cis-1,10b-Dihydronarciclasin-tetraacetat 在 甲醇 、 sodium methylate 作用下， 以 四氢呋喃 为溶剂， 以70%的产率得到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：

  水仙环素 在 吡啶 、 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 23.0 ℃ 、101.33 kPa 条件下， 反应 20.0h， 生成 cis-1,10b-Dihydronarciclasin-tetraacetat
  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

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

  DOI：——

  日期：——
• 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).
• Human Cytochrome P450 Liability Studies of <i>trans</i>-Dihydronarciclasine: A Readily Available, Potent, and Selective Cancer Cell Growth Inhibitor
  作者：James McNulty、Amol Thorat、Nesrin Vurgun、Jerald J. Nair、Emilija Makaji、Denis J. Crankshaw、Alison C. Holloway、Siyaram Pandey

  DOI：10.1021/np100657w

  日期：2011.1.28

  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.