(+)-arctigenin | 84413-77-4

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 呋喃类木脂素
• 英文名称: (+)-arctigenin
• 英文别名: Arctigenin, (+)-；(3S,4S)-4-[(3,4-dimethoxyphenyl)methyl]-3-[(4-hydroxy-3-methoxyphenyl)methyl]oxolan-2-one
• CAS: 84413-77-4
• 化学式: C₂₁H₂₄O₆
• 分子量: 372.418
• InChiKey: NQWVSMVXKMHKTF-CVEARBPZSA-N

物化性质

• 沸点：
  567.0±45.0 °C(Predicted)
• 密度：
  1.227±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+)-arctigenin 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以54%的产率得到2-(3,4-dimethoxybenzyl)-3-(4-hydroxy-3-methoxybenzyl)butane-1,4-diol
  参考文献：
  名称：

  Novel (-)-arctigenin derivatives inhibit signal transducer and activator of transcription 3 phosphorylation and P-glycoprotein function resensitizing multidrug resistant cancer cells in vitro and in vivo

  摘要：

  DOI：

  10.1016/j.ejphar.2023.176146
• 作为产物：
  描述：

  ((3,4-dimethoxyphenyl)methylene)bis(phenylsulfane) 在 sodium tetrahydroborate 、 正丁基锂 、 地昔帕明 、 nickel dichloride 作用下， 反应 9.0h， 生成 (+)-arctigenin
  参考文献：
  名称：

  酚二苄基丁内酯的高价碘氧化制备四氢二苯并环辛烯木脂素和螺二烯酮。

  摘要：

  根据在反应中允许的时间长度，在三氟乙醇中用Phl（OCOCF 3）2处理二苄基丁内酯18，主要产物为螺二烯酮28或四氢二苯并环辛烯29。第二dibenzylbutyrolactone的反应19相同的条件下给出的产品33，34，36和38，而20给出了43直接。这些反应提供了螺二烯酮如28和33的第一批合成物，被假定为四氢二苯并环辛烯木脂素生物合成的中间体。

  DOI：

  10.1016/0040-4020(95)00960-4

文献信息

• Design and Synthesis of Novel Arctigenin Analogues for the Amelioration of Metabolic Disorders
  作者：Shudong Duan、Suling Huang、Jian Gong、Yu Shen、Limin Zeng、Ying Feng、Wenming Ren、Ying Leng、Youhong Hu

  DOI：10.1021/acsmedchemlett.5b00007

  日期：2015.4.9

  compounds. The structure–activity relationship study led to the discovery of key substitution patterns on the lactone motif that govern 2-deoxyglucose uptake activities. The results show that replacement of the para-hydroxyl group of the C-2 benzyl moiety of arctigenin by Cl has a pronounced effect on uptake activity. Specifically, analogue 2p, which contains the p-Cl substituent, stimulates glucose uptake

  制备天然产物（-）-arctigenin（腺苷一磷酸活化蛋白激酶的活化剂）的类似物，以评估其对L6肌管中2-脱氧葡萄糖摄取的影响，并可能用于缓解代谢异常。发现外消旋arctigenin 2a显示出与（-）-arctigenin类似的摄取增强。结果，利用外消旋化合物进行了SAR研究。通过结构-活性关系研究，发现内酯基序上的关键取代模式可控制2-脱氧葡萄糖的摄取活性。结果表明，用Cl替代arctigenin的C-2苄基部分的对羟基具有对摄取活性的显着影响。具体来说，模拟2p含有p -Cl取代基的L6可以刺激L6肌管中的葡萄糖摄取和脂肪酸氧化。
• Preparation of tetrahydrodibenzocyclooctene lignans and spirodienones by hypervalent iodine oxidation of phenolic dibenzylbutyrolactones.
  作者：Robert S. Ward、Andrew Pelter、Atef Abd-El-Ghani

  DOI：10.1016/0040-4020(95)00960-4

  日期：1996.1

  Treatment of the dibenzylbutyrolactone 18 with Phl(OCOCF3)2 in trifluoroethanol gives as the major product either the spirodienone 28 or the tetrahydrodibenzocyclooctene 29, depending upon the length of time allowed for the reaction. Reaction of a second dibenzylbutyrolactone 19 under the same conditions gives the products 33, 34, 36 and 38, while 20 gives 43 directly. These reactions provide the first

  根据在反应中允许的时间长度，在三氟乙醇中用Phl（OCOCF 3）2处理二苄基丁内酯18，主要产物为螺二烯酮28或四氢二苯并环辛烯29。第二dibenzylbutyrolactone的反应19相同的条件下给出的产品33，34，36和38，而20给出了43直接。这些反应提供了螺二烯酮如28和33的第一批合成物，被假定为四氢二苯并环辛烯木脂素生物合成的中间体。
• Oxidative cyclisation of cis- and trans-2,3-dibenzylbutyrolactones using ruthenium tetra(trifluoroacetate)
  作者：Robert S Ward、David D Hughes

  DOI：10.1016/s0040-4020(01)00273-3

  日期：2001.4

  A series of cis- and trans-2,3-dibenzylbutyrolactones have been synthesised and subjected to oxidative cyclisation using ruthenium tetra(trifluoroacetate) affording dibenzocyclooctadiene lactones belonging to the stegane and isostegane series of lignans.

  已经合成了一系列顺式和反式-2,3-二苄基丁内酯，并使用四（三氟乙酸）钌进行氧化环化，得到属于木脂烷和异庚烷系列的二苯并环辛二烯内酯。
• Anticancer Activity of (±)-Kusunokinin Derivatives towards Cholangiocarcinoma Cells
  作者：Thidarath Rattanaburee、Patpanat Sermmai、Kornthip Tangthana-umrung、Tienthong Thongpanchang、Potchanapond Graidist

  DOI：10.3390/molecules27238291

  日期：——

  This study aimed to investigate the cytotoxicity and anticancer activity of (±)-kusunokinin derivatives ((±)-TTPG-A and (±)-TTPG-B). The cytotoxicity effect was performed on human cancer cells, including breast cancer, cholangiocarcinoma, colon and ovarian cancer-cells, compared with normal cells, using the MTT assay. Cell-cycle arrest and apoptosis were detected using flow-cytometry analysis. We found that (±)-TTPG-B exhibited the strongest cytotoxicity on aggressive breast-cancer (MDA-MB-468 and MDA-MB-231) and cholangiocarcinoma (KKU-M213), with an IC50 value of 0.43 ± 0.01, 1.83 ± 0.04 and 0.01 ± 0.001 µM, respectively. Interestingly, (±)-TTPG-A and (±)-TTPG-B exhibited less toxicity than (±)-kusunokinin (9.75 ± 0.39 µM) on L-929 cells (normal fibroblasts). Moreover, (±)-TTPG-A predominated the ell-cycle arrest at the S phase, while (±)-TTPG-B caused cell arrest at the G0/G1 phase, in the same way as (±)-kusunokinin in KKU-M213 cells. Both (±)-TTPG-A and (±)-TTPG-B induced apoptosis and multi-caspase activity more than (±)-kusunokinin. Taken together, we conclude that (±)-TTPG-A and (±)-TTPG-B have a strong anticancer effect on cholangiocarcinoma. Moreover, (±)-TTPG-B could be a potential candidate compound for breast cancer and cholangiocarcinoma in the future.

  本研究旨在探讨(±)-kusunokinin 衍生物（(±)-TTPG-A 和 (±)-TTPG-B）的细胞毒性和抗癌活性。采用 MTT 法对人类癌细胞（包括乳腺癌、胆管癌、结肠癌和卵巢癌细胞）与正常细胞进行了细胞毒性比较。使用流式细胞仪分析检测细胞周期停滞和细胞凋亡。我们发现，(±)-TTPG-B 对侵袭性乳腺癌（MDA-MB-468 和 MDA-MB-231）和胆管癌（KKU-M213）的细胞毒性最强，IC50 值分别为 0.43 ± 0.01、1.83 ± 0.04 和 0.01 ± 0.001 µM。有趣的是，(±)-TTPG-A 和(±)-TTPG-B 对 L-929 细胞（正常成纤维细胞）的毒性低于(±)-kusunokinin（9.75 ± 0.39 µM）。此外，在 KKU-M213 细胞中，(±)-TTPG-A 主要导致细胞周期停滞在 S 期，而(±)-TTPG-B 则导致细胞停滞在 G0/G1 期，这与(±)-kusunokinin 的作用方式相同。(±)-TTPG-A和(±)-TTPG-B都比(±)-kusunokinin更能诱导细胞凋亡和多天冬酶活性。综上所述，我们认为(±)-TTPG-A和(±)-TTPG-B对胆管癌有很强的抗癌作用。此外，(±)-TTPG-B 未来可能成为乳腺癌和胆管癌的候选化合物。
• Discovery of stereospecific cytotoxicity of (8R,8′R)-trans-arctigenin against insect cells and structure-activity relationship on aromatic ring
  作者：Satoshi Yamauchi、Asuka Nishimoto、Hisashi Nishiwaki、Kosuke Nishi、Takuya Sugahara

  DOI：10.1016/j.bmcl.2020.127191

  日期：2020.7

  One of the arctigenin stereoisomers, (8R,8'R)-trans-form 1, showed stereospecific cytotoxicity against insect cells, Sf9 and NIAS-AeAl-2 cells. By the comparison with other stereoisomers, the most importance of the 8'R stereochemistry for the higher activities was clarified. On the other hand, the wider range of activity level among stereoisomers against cancer cells, HL-60, was not observed. The structure-activity relationship research using derivatives bearing (8R,8'R)-trans-form was performed to show the same level of activities of 3-iodo, 4-iodo, and 3,4-methylenedioxy derivatives 28, 29, and 36 as (8R,8'R)-trans-arctigenin 1. In the examination of thiono derivatives, 4-iodo thiono and 3,4-methylenedioxy thiono derivatives 66, 67 showed similar level of activities to that of (8R,8'R)-trans-arctigenin 1. The expression of ribosomal 28S rRNA gene of Sf9 cells was increased by (8R,8'R)-trans-arctigenin 1, whereas a degradation of DNA was not observed.