(5'R,7R,8R,8aS)-5'-呋喃-3-基-4,7-二甲基螺[1,4a,5,6,7,8a-六氢萘-8,3'-四氢呋喃]-2,2'-二酮 | 72548-29-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: (5'R,7R,8R,8aS)-5'-呋喃-3-基-4,7-二甲基螺[1,4a,5,6,7,8a-六氢萘-8,3'-四氢呋喃]-2,2'-二酮
• 中文别名: 1-哌嗪乙胺,4-(羟基亚硝基氨基)-(9CI)
• 英文名称: trans-dehydrocrotonin
• 英文别名: dehydrocrotonin；(4aR,5'R,7R,8R,8aS)-5'-(furan-3-yl)-4,7-dimethylspiro[1,4a,5,6,7,8a-hexahydronaphthalene-8,3'-oxolane]-2,2'-dione
• CAS: 72548-29-9
• 化学式: C₁₉H₂₂O₄
• 分子量: 314.381
• InChiKey: PHTWCRQCDPNVLQ-WCARXYILSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  56.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (5'R,7R,8R,8aS)-5'-呋喃-3-基-4,7-二甲基螺[1,4a,5,6,7,8a-六氢萘-8,3'-四氢呋喃]-2,2'-二酮 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以80%的产率得到2-hydrazone-dehydrocrotonin
  参考文献：
  名称：

  Synthesis of New trans-Dehydrocrotonin Nitrogenated Derivatives and their Cytotoxic and DNA-Topoisomerase I Inhibitory Activities

  摘要：

  A new series of 19-nor-clerodane diterpene derivatives was synthesized from the natural trans-dehydrocrotonin obtained from stem barks of Croton cajucara (Euphorbiaceae), a native medicinal plant of the Brazilian Amazon. The new derivatives were obtained by changes in the ketone moiety of trans-dehydrocrotonin leading to nitrogenated derivatives which are: three substituted hydrazine diterpenes, oxime, and methyloxime. The cytotoxic effect of the diterpene derivatives was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay against Ehrlich carcinoma and K562 human leukemia cells. The cytotoxic activity of the hydrazine and oxime semi-synthetic derivatives was better than the one of the natural product trans-dehydrocrotonin. Moreover, all diterpenes were tested for their DNA topoisomerase I inhibitory activity, and the most effective one, in general, was observed to the phenyl-hydrazone derivative. Results indicated that the topoisomerase I inhibitory effect is correlated with the cytotoxic activity.

  DOI：

  10.21577/0103-5053.20170121

文献信息

• New derivative of trans-dehydrocrotonin isolated from Croton cajucara shows reduced cytotoxic and genotoxic effects in hepatocellular carcinoma (HepG2) cell line
  作者：Vinícius Silva de Carvalho、Karina Motta Melo Lima、Luana França Calandrini de Azevedo、Paulo Alexandre Panarra Ferreira Gomes das Neves、Rosivaldo dos Santos Borges、Cleusa Yoshiko Nagamachi、Julio Cesar Pieczarka

  DOI：10.1016/j.toxicon.2022.106940

  日期：2022.12

  consumption is associated with hepatotoxic effects due to the furan ring present in the molecule. This group is responsible for toxicity reactions in other drugs. In this work, we inserted a COOH group into the molecule to prevent the formation of toxic intermediates. We assessed the cytotoxicity and genotoxicity of both molecules on HepG2 cells. Results showed that the new derivative (CCTN) is less cytotoxic

  巴豆(Euphorbiales, Euphorbiaceae) 植物广泛分布于亚马逊地区，那里的人们食用其叶子和茎皮来治疗多种疾病。次级代谢产物反式- 脱氢巴豆素 (DCTN) 主要负责这种植物的生物活性。然而，由于分子中存在呋喃环，长期食用与肝毒性作用有关。该组负责其他药物的毒性反应。在这项工作中，我们在分子中插入了一个 COOH 基团，以防止有毒中间体的形成。我们评估了两种分子对 HepG2 细胞的细胞毒性和遗传毒性。结果表明，新衍生物 (CCTN) 的细胞毒性较小，并且在任何测试浓度下都不会降低细胞活力。通过彗星和微核试验评估，遗传毒性也有所降低。因此，新的衍生物似乎很有前途，应该进行额外的测试来评估其治疗活性。
• Synthesis, NMR data and theoretical study of semi-synthetic derivatives from trans-dehydrocrotonin
  作者：Breno Almeida Soares、Maria Aparecida Medeiros Maciel、Rosane Nora Castro、Carlos R. Kaiser、Caio Lima Firme

  DOI：10.1016/j.molstruc.2015.12.045

  日期：2016.3

  1D and 2D NMR spectral data. Comparison of NMR data from natural source of t -CTN was done to confirm the stereochemical authenticity of semi-synthetic t -CTN. Calculated NMR data for all described derivatives (semi-synthetic t -CTN and its t -CTN-OL epimeric mixture) were performed using B3LYP/6-311G++(d,p) level of theory which validated our previously developed NMR theoretical protocol for structural

  摘要 在这项工作中，19-nor-diterpenoid clerodane 型脱氢巴豆素 (t-DCTN) 是两步合成程序的主要来源。t-DCTN 的催化氢化在高度立体定向反应中提供了半合成的反式巴豆素 (t-CTN)，DFT 计算证实了这一点。t-DCTN 的不饱和羰基被 NaBH 4 /EtOH 还原，提供差向异构 α-OH 和 β-OH 混合物，称为 t-CTN-OL。差向异构化合物结构 t-CTN-α-OL 和 t-CTN-β-OL 均通过 1D 和 2D NMR 光谱数据阐明。对来自 t-CTN 天然来源的 NMR 数据进行比较，以确认半合成 t-CTN 的立体化学真实性。使用 B3LYP/6-311G++(d, p) 验证我们之前开发的用于有机分子结构分析的 NMR 理论方案的理论水平。使用 t-CTN 分子中原子量子理论 (QTAIM) 的拓扑数据量化和限定了其最稳定构象异构体的分子内相互作用。
• Anti-Tumour Activity of Two 19-Nor-clerodane Diterpenes, trans-Dehydrocrotonin and trans-Crotonin, from Croton cajucara
  作者：Noema F. Grynberg、Aurea Echevarria、Juliana E. Lima、Sônia S. R. Pamplona、Angelo C. Pinto、Maria Aparecida M. Maciel

  DOI：10.1055/s-1999-14042

  日期：1999.12

  The effects of two nor-diterpenes, trans-dehydrocrotonin (DCTN) and trans-crotonin (CTN) from Croton cajucara (Euphorbiaceae), on the survival of mice bearing Sarcoma 180 and Ehrlich carcinoma ascitic tumours, on the proliferation of cultured Ehrlich cells and TNFα activity were determined. When the mice were treated with 80 and 120 mg/kg of DCTN or 38 mg/kg of 5-FU a significant anti-tumour activity was obtained (%T/C of 128 - 140). The cytotoxicity against Ehrlich carcinoma was 16 μM for DCTN and CTN whereas the flavonoid quercetin was cytotoxic at 44 μM in 48 h cell culture. No apoptosis was seen on in vitro electrophoresis of DNA extracted from the tumour cells treated with DCTN and CTN. A significant TNFα activity was detected in Ehrlich tumour-bearing mice treated with DCTN suggesting an enhanced immune function.

  对来自巴豆（大戟科）的两种去二萜类化合物——反式脱氢巴豆素（DCTN）和反式巴豆素（CTN）对小鼠携带肉瘤180和艾氏癌腹水瘤的存活率、培养的艾氏细胞增殖和TNFα活性的影响进行了测定。当小鼠接受80和120 mg/kg的DCTN或38 mg/kg的5-FU治疗时，获得了显著的抗肿瘤活性（%T/C为128-140）。DCTN和CTN对艾氏癌的细胞毒性为16 µM，而黄酮类化合物槲皮素在48 h细胞培养中的细胞毒性为44 µM。在用DCTN和CTN处理过的肿瘤细胞中提取的DNA的体外电泳中未观察到细胞凋亡。在用DCTN治疗的艾氏癌小鼠中检测到显著的TNFα活性，表明免疫功能增强。
• Nor-clerodane diterpenes from Croton cajucara
  作者：Hideji Itokawa、Yoshitatsu Ichihara、Hiroshi Kojima、Kinzo Watanabe、Kolchi Takeya

  DOI：10.1016/s0031-9422(00)97821-x

  日期：1989.1

  Abstract A new nor -clerodane diterpene, t -crotonin, was isolated from the cortices of Croton cajucara along with the previously isolated diterpene, of which the structure was not confirmed, dehydrocrotonin. The structures of these compounds were elucidated by chemical and spectroscopic methods.

  摘要 从巴豆皮层中分离到了一种新的去甲克罗丹二萜，t-巴豆素，以及先前分离的二萜，其结构未得到证实，脱氢巴豆素。这些化合物的结构通过化学和光谱方法阐明。
• ITOKAWA, HIDEJI;ICHIHARA, YOSHITATSU;KOJIMA, HIROSHI;WATANABE, KINZO;TAKE+, PHYTOCHEMISTRY, 28,(1989) N, C. 1667-1669
  作者：ITOKAWA, HIDEJI、ICHIHARA, YOSHITATSU、KOJIMA, HIROSHI、WATANABE, KINZO、TAKE+

  DOI：——

  日期：——