13-(2-ethoxy-2-oxoethyl)-9,10-dimethoxy-5,6-dihydrobenzo[g]-1,3-benzodioxolo[5,6-a]quinolizinium bromide

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 原小檗碱生物碱及其衍生物
• 英文名称: 13-(2-ethoxy-2-oxoethyl)-9,10-dimethoxy-5,6-dihydrobenzo[g]-1,3-benzodioxolo[5,6-a]quinolizinium bromide
• 英文别名: Ethyl 2-(16,17-dimethoxy-5,7-dioxa-13-azoniapentacyclo[11.8.0.02,10.04,8.015,20]henicosa-1(13),2,4(8),9,14,16,18,20-octaen-21-yl)acetate;bromide
• 化学式: Br*C₂₄H₂₄NO₆
• 分子量: 502.362
• InChiKey: BVXRXIRQRUAJKD-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.21
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  67.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  13-(2-ethoxy-2-oxoethyl)-9,10-dimethoxy-5,6-dihydrobenzo[g]-1,3-benzodioxolo[5,6-a]quinolizinium bromide 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 10.0h， 以94%的产率得到2-(16,17-Dimethoxy-5,7-dioxa-13-azoniapentacyclo[11.8.0.02,10.04,8.015,20]henicosa-1(13),2,4(8),9,14,16,18,20-octaen-21-yl)acetic acid;chloride
  参考文献：
  名称：

  <p>13-[CH2CO-Cys-(Bzl)-OBzl]-Berberine: Exploring The Correlation Of Anti-Tumor Efficacy With ROS And Apoptosis Protein</p>

  摘要：

  Background: The discovery of novel derivative of berberine (BBR) having higher antitumor activity in vivo is of clinical importance. In this profile, 13-[CH2CO-Cys-(Bzl)-OBzl]-berberine (13-Cys-BBR) was prepared for related assays.Purpose: The object of preparation and evaluation is to show the advantages of 13-Cys-BBR over BBR in both in vitro and in vivo anti-tumor actions, furthermore to correlate the proliferation of cancer cells with ROS formation and anti-apoptosis protein (XIAP) expression inside cancer cells.Methods: Transwell chamber was used to simulate the intestinal and cell wall for bioavailability evaluation; MTT assay was used to evaluate the in vitro anti-proliferation activity; fluorescein isothiocyanate content was used to represent ROS level in HCT-8 cells; Western blot assay was used to quantify the expression of XIAP, caspase-3, and poly ADP-ribose polymerase in HCT-8 cells; and 5180 mouse model was used to evaluate the in vivo antitumor activity.Results: In vitro the IC50 values (similar to 15-40 mu M) of 13-Cys-BBR against the proliferation of eight cancer cell lines were significantly lower than those of BBR (similar to 25-140 mu M); the content of ROS formed inside HCT-8 cells treated by 13-Cys-BBR was similar to 3.44-folds higher than that inside HCT-8 cells treated by BBR; the expression of XIAP in HCT-8 cells treated by 13-Cys-BBR was similar to 1.21-folds lower than that in HCT-8 cells treated by BBR; the tumor weight of 5180 mice orally treated by 2 mu mol/kg/day of 13-Cys-BBR (similar to 1.5 g) was significantly lower than that of 5180 mice orally treated by 2 mu mol/kg/day of BBR (similar to 2.5 g); and the active pocket of XIAP was more suitable for 13-Cys-BBR than for BBR.Conclusion: The anti-tumor action correlates with ROS and apoptosis protein, which suggests 13-Cys-BBR is a promising candidate for preclinical study.

  DOI：

  10.2147/ott.s231035
• 作为产物：
  描述：

  盐酸小檗碱 在 sodium iodide 、 sodium hydroxide 作用下， 以 乙腈 为溶剂， 反应 4.0h， 生成 13-(2-ethoxy-2-oxoethyl)-9,10-dimethoxy-5,6-dihydrobenzo[g]-1,3-benzodioxolo[5,6-a]quinolizinium bromide
  参考文献：
  名称：

  13位小Ber碱衍生物的合成和抗菌活性的评估。

  摘要：

  已知天然植物分子小ber碱的生物活性受结构修饰的影响，主要在9和/或13位。合成了一系列新的13位取代的小ber碱衍生物，并使用多种微生物进行了抗微生物活性评估。与人类疾病有关。与原始分子小ber碱相反，在对分枝杆菌，白色念珠菌和革兰氏阳性细菌的微生物敏感性测试中，发现了几种衍生物具有较强的活性，包括幼稚或耐药的蜡状芽孢杆菌，金黄色葡萄球菌和化脓性链球菌最小抑菌浓度（MIC）为3.12至6.25 µM。在所测试的各种革兰氏阴性菌株，黄连的衍生物只发现活性上幽门螺杆菌和弧菌溶藻弧菌（MIC值为1.5–3.12 µM）。对人细胞进行的细胞毒性试验表明，抗菌小碱衍生物引起的毒性低，从而产生了良好的治疗指数值。此外，一种机械方法证明，与引起膜透化，DNA断裂或与FtsZ蛋白相互作用的已知小already碱衍生物相反，本研究中所述的活性衍生物通过抑制肽聚糖或RNA的合成起作用。总体而言，这项研究表明

  DOI：

  10.3390/antibiotics9070381

文献信息

• The synthesis and antistaphylococcal activity of 9, 13-disubstituted berberine derivatives
  作者：Jing Wang、Teng Yang、Huang Chen、Yun-Nan Xu、Li-Fang Yu、Ting Liu、Jie Tang、Zhengfang Yi、Cai-Guang Yang、Wei Xue、Fan Yang

  DOI：10.1016/j.ejmech.2017.01.012

  日期：2017.2

  antibacterial activities against Staphylococcus aureus, including Newman strain and multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108, and NRS-271). Compound 20 shows the most potent activity against the growth of Newman strain, with a MIC value of 0.78 μg/mL, which is comparable with the positive control vancomycin. In addition, compound 20, 21, and 33 are highly antistaphylococcal active against

  合成了一系列新颖的9、13-双取代的小ber碱衍生物，并评估了其对金黄色葡萄球菌的抗菌活性，包括纽曼菌株和耐多药菌株（NRS-1，NRS-70，NRS-100，NRS-108和NRS-271）。化合物20对纽曼菌株的生长表现出最强的活性，MIC值为0.78μg/ mL，与阳性对照万古霉素相当。另外，化合物20，21和33是高度antistaphylococcal活性对耐多药的五种菌株的金黄色葡萄球菌，MIC值为0.78–1.56μg/ mL。值得注意的是，这些抗菌活性化合物在MIC浓度下对人成纤维细胞（HAF）细胞的活力没有明显的毒性。
• 8-Allyldihydroberberine as an Alternative Precursor for the Synthesis of 13-Substituted Berberine Derivatives
  作者：John B. Bremner、Siritron Samosorn

  DOI：10.1071/ch03054

  日期：——

  An alternative route to 13-substituted derivatives of the biologically active alkaloid berberine has been developed based on the key synthetic precursor, 8-allyldihydroberberine.

  在关键合成前体 8-烯丙基二氢小檗碱的基础上，开发出了生物活性生物碱小檗碱 13-取代衍生物的替代途径。