neoanhydropodophyllol | 62287-47-2

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 芳基四氢萘木脂素
• 英文名称: neoanhydropodophyllol
• 英文别名: anhydropodophyllol；[(1R,11R,12R,15R)-11-(3,4,5-trimethoxyphenyl)-5,7,14-trioxatetracyclo[10.2.1.02,10.04,8]pentadeca-2,4(8),9-trien-15-yl]methanol
• CAS: 62287-47-2
• 化学式: C₂₂H₂₄O₇
• 分子量: 400.428
• InChiKey: GAPFRQMOPFLDIS-YJPXFSGGSA-N

物化性质

• 沸点：
  533.3±50.0 °C(Predicted)
• 密度：
  1.292±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  75.6
• 氢给体数：
  1
• 氢受体数：
  7

制备方法与用途

生物活性 Neoanhydropodophyllol 是一种环聚糖衍生物，展现出显著的抗肿瘤活性。研究显示，它对多种类型的癌细胞（包括白血病、肺癌和结肠癌）具有细胞毒性作用。

反应信息

• 作为反应物：
  描述：

  neoanhydropodophyllol 在 dipotassium peroxodisulfate 、 copper(II) sulfate 作用下， 以 水 、 乙腈 为溶剂， 反应 0.5h， 以34%的产率得到8H-5,3-dioxolo[4,5-h][2]benzoxepin, 9,11-epoxymethano-9-(3,4,5-trimethoxyphenyl)-
  参考文献：
  名称：

  Modes of Methyleneoxy Bridging and Their Effect on Tetrahydronaphthalene Lignan Cytotoxicity

  摘要：

  Dioxatricyclodecane, oxabicyclooctane, and benzodihydropyran derivatives of alpha-conidendrin (ACON), podophyllotoxin (PT), and sikkimotoxin (SK) were prepared to learn which methyleneoxy bridging modes and arene and aryl substituents coincided with high cytotoxicity. PT-derived dioxatricyclodecane 14 showed in vitro activity at 10(-8) M. SK analogue 12 was less active, and ACON analogue 11 was inactive at 10(-4) M. In vivo intraperitoneal and subcutaneous activities of 14 were observed. In vitro cytotoxicities were higher for oxabicyclooctanes when hydroxymethyl group and methyleneoxy bridge were cis, as in deoxypicropodophyllin analog 20, rather than trans, as in PT analogue 5. Acetylation of the hydroxymethyl group of 20 lowered activities, whereas acetylation of 5 increased or lowered activities. Reduction of the hydroxymethyl group of 5 to a methyl group increased cytotoxicities. Molecular dynamics indicated the THN scaffold of benzodihydropyrans was conformationally mobile, but scaffolds of oxabicyclooctanes and dioxatricyclodecanes were immobile. Each of three PT-benzodihydropyrans was less active than its oxabicyclooctane counterpart.

  DOI：

  10.1021/jm020158p
• 作为产物：
  描述：

  鬼臼毒素 在 盐酸 、 lithium aluminium tetrahydride 作用下， 以 乙醚 、 氯仿 为溶剂， 反应 5.0h， 生成 neoanhydropodophyllol
  参考文献：
  名称：

  Castro, M. A.; Gordaliza, M.; Corral, J. M. Miguel del, Organic Preparations and Procedures International, 1994, vol. 26, # 5, p. 539 - 548

  摘要：

  DOI：

文献信息

• Synthesis of podophyllotoxin analogues: δ-lactone-containing picropodophyllin, podophyllotoxin and 4′-demethyl-epipodophyllotoxin derivatives
  作者：Philippe Meresse、Claude Monneret、Emmanuel Bertounesque

  DOI：10.1016/j.tet.2004.01.017

  日期：2004.3

  cyano group, led to the trans δ-lactone 5 (7 steps from 1 and 6% overall yied) with a small amount of its C-4 epimer 6. The synthesis of non-epimerizable δ-lactone analogues of 4′-demethyl-epipodophyllotoxin 7 and of 4-demethyl podophyllotoxin 8 are also reported. The synthesis of 7 and 8 was based upon the reduction of the γ-lactone ring of 4′-demethyl-4-epipodophyllotoxin followed by selective protection

  已经制备了鬼臼毒素的不可表位的顺式和反式δ-内酯类似物。因此，通过将γ内酯环还原成反式二醇，选择性保护4-OH和11-OH作为亚苄基乙缩醛，鬼臼毒素1的合成已经完成了8个步骤，并且鬼臼毒素1的总收率为4％，从而实现了顺式异构体4的合成。，以及Wittig在C-13处的延伸，以及C-2处的构型反转。在C-13处具有相同的伸长率，但通过形成甲磺酸酯和引入氰基基团，产生了带有少量C-4差向异构体的反式δ-内酯5（从1和6％的总收率起7步）6。还报道了4'-脱甲基-表鬼臼毒素7和4-脱甲基鬼臼毒素8的不可表位的δ-内酯类似物的合成。7和8的合成是基于还原4'-去甲基-4-表鬼臼毒素的γ-内酯环，然后在C-11处进行选择性保护，并在C-13处进行延伸。（总产量的8-15％和4％）。化合物4，5和7没有对L1210鼠白血病显示体外相关的细胞毒性。
• Synthesis and antineoplastic activity of cyclolignan aldehydes
  作者：Marina Gordaliza、M Angeles Castro、José M Miguel del Corral、M Luisa López-Vázquez、Pablo A. García、M Dolores García-Grávalos、Arturo San Feliciano

  DOI：10.1016/s0223-5234(00)00176-8

  日期：2000.8

  Several aldehydes related to methyl 9-deoxy-9-oxo-alpha-apopicropodophyllate, a selective antitumour agent against the HT-29 colon carcinoma, have been prepared and evaluated for their cytotoxic activities on four neoplastic cell lines (P-388, A-549, HT-29 and MEL-28). All of them lacked the lactone ring but maintained their cytotoxicity at, or under, the microM level.

  已经制备了几种与HT-29结肠癌的选择性抗肿瘤药9-脱氧-9-氧代-α-阿朴二十碳五烯酸甲酯有关的醛，并评估了它们对四种肿瘤细胞系的细胞毒活性（P-388，A- 549，HT-29和MEL-28）。他们所有人都没有内酯环，但将细胞毒性维持在microM水平或以下。
• Cytotoxic cyclolignans related to podophyllotoxin
  作者：Marina Gordaliza、José M Miguel del Corral、M Angeles Castro、Pablo A Garcı́a-Garcı́a、Arturo San Feliciano

  DOI：10.1016/s0014-827x(01)01030-8

  日期：2001.4

  The cyclolignan family of natural products includes compounds with important antineoplastic and antiviral properties such as podophyllotoxin and two of their semisynthetic derivatives, etoposide and teniposide. The latter are included in a wide variety of cancer chemotherapy protocols. Due to these biological activities, cyclolignans have been the objective of numerous studies focused to prepare better and safer anticancer drugs. Several cyclolignans related to podophyllotoxin have, been prepared and evaluated for their cytotoxic activities on four neoplastic cell lines (P-388, A-549, HT-29 and MEL-28); some of them have antiviral and immunosuppressive activities. (C) 2001 Elsevier Science S.A. All rights reserved.
• Castro, M. A.; Gordaliza, M.; Corral, J. M. Miguel del, Organic Preparations and Procedures International, 1994, vol. 26, # 5, p. 539 - 548
  作者：Castro, M. A.、Gordaliza, M.、Corral, J. M. Miguel del、Feliciano, A. San

  DOI：——

  日期：——
• Modes of Methyleneoxy Bridging and Their Effect on Tetrahydronaphthalene Lignan Cytotoxicity
  作者：Robert T. LaLonde、Frank Ramdayal、Anatole Sarko、Koichi Yanai、Mianji Zhang

  DOI：10.1021/jm020158p

  日期：2003.3.1

  Dioxatricyclodecane, oxabicyclooctane, and benzodihydropyran derivatives of alpha-conidendrin (ACON), podophyllotoxin (PT), and sikkimotoxin (SK) were prepared to learn which methyleneoxy bridging modes and arene and aryl substituents coincided with high cytotoxicity. PT-derived dioxatricyclodecane 14 showed in vitro activity at 10(-8) M. SK analogue 12 was less active, and ACON analogue 11 was inactive at 10(-4) M. In vivo intraperitoneal and subcutaneous activities of 14 were observed. In vitro cytotoxicities were higher for oxabicyclooctanes when hydroxymethyl group and methyleneoxy bridge were cis, as in deoxypicropodophyllin analog 20, rather than trans, as in PT analogue 5. Acetylation of the hydroxymethyl group of 20 lowered activities, whereas acetylation of 5 increased or lowered activities. Reduction of the hydroxymethyl group of 5 to a methyl group increased cytotoxicities. Molecular dynamics indicated the THN scaffold of benzodihydropyrans was conformationally mobile, but scaffolds of oxabicyclooctanes and dioxatricyclodecanes were immobile. Each of three PT-benzodihydropyrans was less active than its oxabicyclooctane counterpart.