通过重原子类似物 7-(4-溴苯甲酰基）异槲皮苷 A 的 X 射线晶体学确定异水飞蓟宾 A 的绝对构型。
Absolute configuration of isosilybin A by X-ray crystallography of the heavy atom analogue 7-(4-Bromobenzoyl)isosilybin A.
机构信息
Department of Chemistry and Biochemistry, University of North Carolina at Greensboro , Greensboro, North Carolina 27402, United States.
出版信息
J Nat Prod. 2012 Nov 26;75(11):1879-81. doi: 10.1021/np3005369. Epub 2012 Nov 1.
Abstract
Isosilybin A (1) is one of the major flavonolignans that constitute silymarin, an extract of the fruits (achenes) of milk thistle (Silybum marianum). The chemistry of the Silybum flavonolignans has been studied for over four decades, and the absolute configuration of 1 has been determined previously by electronic circular dichroism and X-ray crystallography via correlating the relative configuration of the phenylpropanoid moiety to the established absolute configuration of the 3-hydroxyflavanone portion of the molecule. Herein we report the X-ray crystallographic structure of the product of the reaction of 1 with 4-bromobenzoyl chloride, and, thus, the absolute configuration of 1 was established as (2R, 3R, 7″R, 8″R) directly via X-ray crystallography of an analogue that incorporated a heavy atom. The results were consistent with previously reported assignments and verified the absolute configuration of the diastereoisomer of 1, isosilybin B, and the related diastereoisomeric regioisomers, silybin A and silybin B.
摘要
水飞蓟宾 A（1）是构成水飞蓟素的主要黄酮木脂素之一，水飞蓟素是奶蓟（水飞蓟）果实（瘦果）的提取物。四十多年来一直在研究水飞蓟黄酮木脂素的化学，通过将苯丙素部分的相对构型与分子中 3-羟基黄酮部分的已建立的绝对构型相关联，以前曾通过电子圆二色性和 X 射线晶体学确定 1 的绝对构型。在此，我们报告了 1 与 4-溴苯甲酰氯反应产物的 X 射线晶体结构，因此，通过引入重原子的类似物的 X 射线晶体学直接确定了 1 的绝对构型为（2R，3R，7″R，8″R）。结果与先前报道的分配结果一致，并验证了 1 的非对映异构体，水飞蓟宾 B 以及相关的非对映异构体区域异构体，水飞蓟宾 A 和水飞蓟宾 B 的绝对构型。
相似文献
1
Absolute configuration of isosilybin A by X-ray crystallography of the heavy atom analogue 7-(4-Bromobenzoyl)isosilybin A.通过重原子类似物 7-(4-溴苯甲酰基）异槲皮苷 A 的 X 射线晶体学确定异水飞蓟宾 A 的绝对构型。
J Nat Prod. 2012 Nov 26;75(11):1879-81. doi: 10.1021/np3005369. Epub 2012 Nov 1.
2
Molecular structure and stereochemistry of silybin A, silybin B, isosilybin A, and isosilybin B, Isolated from Silybum marianum (milk thistle).从水飞蓟（奶蓟）中分离得到的水飞蓟宾A、水飞蓟宾B、异水飞蓟宾A和异水飞蓟宾B的分子结构和立体化学
J Nat Prod. 2003 Sep;66(9):1171-4. doi: 10.1021/np030163b.
3
Chemotaxonomic and biosynthetic relationships between flavonolignans produced by Silybum marianum populations.水飞蓟种群产生的黄酮木脂素之间的化学分类学和生物合成关系。
Fitoterapia. 2017 Jun;119:175-184. doi: 10.1016/j.fitote.2017.04.002. Epub 2017 Apr 6.
4
The study of flavonolignan association patterns in fruits of diverging Silybum marianum (L.) Gaertn. chemotypes provides new insights into the silymarin biosynthetic pathway.对不同化学型水飞蓟果实中黄酮木脂素缔合模式的研究为水飞蓟素生物合成途径提供了新见解。
Phytochemistry. 2017 Dec;144:9-18. doi: 10.1016/j.phytochem.2017.08.013. Epub 2017 Sep 1.
5
The effect of milk thistle (Silybum marianum) and its main flavonolignans on CYP2C8 enzyme activity in human liver microsomes.水飞蓟（奶蓟）及其主要黄酮木脂素对人肝微粒体中CYP2C8酶活性的影响。
Chem Biol Interact. 2017 Jun 1;271:24-29. doi: 10.1016/j.cbi.2017.04.025. Epub 2017 Apr 27.
6
Two flavonolignans from milk thistle (Silybum marianum) inhibit CYP2C9-mediated warfarin metabolism at clinically achievable concentrations.水飞蓟素（奶蓟草）中的两种类黄酮木质素可在临床可达到的浓度下抑制 CYP2C9 介导的华法林代谢。
J Pharmacol Exp Ther. 2010 Mar;332(3):1081-7. doi: 10.1124/jpet.109.161927. Epub 2009 Nov 24.
7
Flavonolignans from Aspergillus iizukae, a fungal endophyte of milk thistle (Silybum marianum).奶蓟（水飞蓟）内生真菌 Aspergillus iizukae 的类黄酮木脂素。
J Nat Prod. 2014 Feb 28;77(2):193-9. doi: 10.1021/np400955q. Epub 2014 Jan 23.
8
Large-scale isolation of flavonolignans from Silybum marianum extract affords new minor constituents and preliminary structure-activity relationships.从水飞蓟宾提取物中大规模分离得到黄酮木脂素，获得新的微量成分和初步的构效关系。
Planta Med. 2010 Apr;76(6):644-7. doi: 10.1055/s-0029-1240624. Epub 2009 Nov 25.
9
An assessment of pharmacokinetics and antioxidant activity of free silymarin flavonolignans in healthy volunteers: a dose escalation study.评估健康志愿者中游离水飞蓟素黄酮木脂素的药代动力学和抗氧化活性：剂量递增研究。
Drug Metab Dispos. 2013 Sep;41(9):1679-85. doi: 10.1124/dmd.113.052423. Epub 2013 Jul 8.
10
Variation in the flavonolignan composition of fruits from different Silybum marianum chemotypes and suspension cultures derived therefrom.不同水飞蓟化学型果实及其悬浮培养物中黄酮木脂素成分的差异。
Phytochemistry. 2016 Nov;131:68-75. doi: 10.1016/j.phytochem.2016.09.003. Epub 2016 Sep 14.
引用本文的文献
1
Chirality Matters: Biological Activity of Optically Pure Silybin and Its Congeners.手性很重要：手性纯水飞蓟宾及其同系物的生物活性。
Int J Mol Sci. 2021 Jul 23;22(15):7885. doi: 10.3390/ijms22157885.
2
Opportunities and Limitations for Assigning Relative Configurations of Antibacterial Bislactones using GIAO NMR Shift Calculations.使用 GIAO NMR 位移计算分配抗菌双内酯相对构型的机会和限制。
J Nat Prod. 2021 Apr 23;84(4):1254-1260. doi: 10.1021/acs.jnatprod.0c01309. Epub 2021 Mar 25.
3
Cytotoxic Naphthoquinone Analogues, Including Heterodimers, and Their Structure Elucidation Using LR-HSQMBC NMR Experiments.细胞毒性萘醌类似物，包括杂二聚体，及其使用 LR-HSQMBC NMR 实验进行结构解析。
J Nat Prod. 2021 Mar 26;84(3):771-778. doi: 10.1021/acs.jnatprod.0c00856. Epub 2020 Oct 2.
4
Mutation of an atypical oxirane oxyanion hole improves regioselectivity of the α/β-fold epoxide hydrolase Alp1U.突变非典型环氧化合物氧阴离子穴可提高α/β 折叠环氧化物水解酶 Alp1U 的区域选择性。
J Biol Chem. 2020 Dec 11;295(50):16987-16997. doi: 10.1074/jbc.RA120.015563. Epub 2020 Oct 1.
5
Orthogonal Method for Double-Bond Placement via Ozone-Induced Dissociation Mass Spectrometry (OzID-MS).通过臭氧诱导解离质谱（OzID-MS）进行双键定位的正交方法。
J Nat Prod. 2019 Dec 27;82(12):3421-3431. doi: 10.1021/acs.jnatprod.9b00787. Epub 2019 Dec 11.
6
Determination of the absolute stereostructure of a cyclic azobenzene from the crystal structure of the precursor containing a heavy element.从前体的晶体结构确定含重元素的环状偶氮苯的绝对立体结构。
Beilstein J Org Chem. 2016 Oct 19;12:2211-2215. doi: 10.3762/bjoc.12.212. eCollection 2016.
7
A validated UHPLC-tandem mass spectrometry method for quantitative analysis of flavonolignans in milk thistle (Silybum marianum) extracts.一种经过验证的超高效液相色谱-串联质谱法，用于定量分析水飞蓟（水飞蓟属）提取物中的黄酮木脂素。
J Pharm Biomed Anal. 2016 Jul 15;126:26-33. doi: 10.1016/j.jpba.2016.04.028. Epub 2016 Apr 22.
8
Pannorin B, a new naphthopyrone from an endophytic fungal isolate of Penicillium sp.潘诺林B，一种从青霉属内生真菌分离物中得到的新型萘并吡喃酮
Magn Reson Chem. 2016 Feb;54(2):164-7. doi: 10.1002/mrc.4324. Epub 2015 Sep 14.
9
Phylogenetic and chemical diversity of fungal endophytes isolated from (L) Gaertn. (milk thistle).从水飞蓟（L. Gaertn.）中分离出的真菌内生菌的系统发育和化学多样性。
Mycology. 2015 Jan 2;6(1):8-27. doi: 10.1080/21501203.2015.1009186. Epub 2015 Feb 23.
10
A biomimetic strategy to access the silybins: total synthesis of (-)-isosilybin A.一种获取水飞蓟宾的仿生策略：(-)-异水飞蓟宾A的全合成。
Org Lett. 2015 Jan 2;17(1):98-101. doi: 10.1021/ol503303w. Epub 2014 Dec 17.
本文引用的文献
1
Angiopreventive efficacy of pure flavonolignans from milk thistle extract against prostate cancer: targeting VEGF-VEGFR signaling.水飞蓟素纯黄酮醇对前列腺癌的血管预防作用：靶向 VEGF-VEGFR 信号通路。
PLoS One. 2012;7(4):e34630. doi: 10.1371/journal.pone.0034630. Epub 2012 Apr 13.
2
Synthesis and antiangiogenic activity of new silybin galloyl esters.新型水飞蓟宾酰基酯的合成及抗血管生成活性。
J Med Chem. 2011 Oct 27;54(20):7397-407. doi: 10.1021/jm201034h. Epub 2011 Oct 3.
3
Differential in vitro effects of intravenous versus oral formulations of silibinin on the HCV life cycle and inflammation.水飞蓟宾静脉制剂与口服制剂对 HCV 生命周期和炎症的体外差异作用。
PLoS One. 2011 Jan 28;6(1):e16464. doi: 10.1371/journal.pone.0016464.
4
Isosilybin A induces apoptosis in human prostate cancer cells via targeting Akt, NF-κB, and androgen receptor signaling.水飞蓟宾 A 通过靶向 Akt、NF-κB 和雄激素受体信号通路诱导人前列腺癌细胞凋亡。
Mol Carcinog. 2010 Oct;49(10):902-12. doi: 10.1002/mc.20670.
5
Antimetastatic efficacy of silibinin: molecular mechanisms and therapeutic potential against cancer.水飞蓟宾的抗肿瘤转移疗效：分子机制和治疗癌症的潜力。
Cancer Metastasis Rev. 2010 Sep;29(3):447-63. doi: 10.1007/s10555-010-9237-0.
6
Milk thistle in liver diseases: past, present, future.水飞蓟在肝脏疾病中的应用：过去、现在与未来。
Phytother Res. 2010 Oct;24(10):1423-32. doi: 10.1002/ptr.3207.
7
Multiple effects of silymarin on the hepatitis C virus lifecycle.水飞蓟素对丙型肝炎病毒生命周期的多种影响。
Hepatology. 2010 Jun;51(6):1912-21. doi: 10.1002/hep.23587.
8
Enzymatic kinetic resolution of silybin diastereoisomers.手性拆分水飞蓟宾对映异构体的酶促动力学方法。
J Nat Prod. 2010 Apr 23;73(4):613-9. doi: 10.1021/np900758d.
9
Identification of hepatoprotective flavonolignans from silymarin.从水飞蓟素中鉴定具有肝保护作用的黄酮木脂素。
Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5995-9. doi: 10.1073/pnas.0914009107. Epub 2010 Mar 15.
10
Two flavonolignans from milk thistle (Silybum marianum) inhibit CYP2C9-mediated warfarin metabolism at clinically achievable concentrations.水飞蓟素（奶蓟草）中的两种类黄酮木质素可在临床可达到的浓度下抑制 CYP2C9 介导的华法林代谢。
J Pharmacol Exp Ther. 2010 Mar;332(3):1081-7. doi: 10.1124/jpet.109.161927. Epub 2009 Nov 24.
Zotero 插件