KOR 激动剂中 salvinorin 型的化学合成。
Chemical syntheses of the salvinorin chemotype of KOR agonist.
机构信息
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
出版信息
Nat Prod Rep. 2020 Nov 18;37(11):1478-1496. doi: 10.1039/d0np00028k.
Abstract
Covering: 2000 to 2020 The hallucinogenic diterpene salvinorin A potently and selectively agonizes the human kappa-opioid receptor (KOR). Its unique attributes-lack of a basic nitrogen, rapid brain penetrance, short half-life-combined with the potential of KOR as an emerging target for analgesics have stimulated extensive medicinal chemistry based on semi-synthesis from extracts of Salvia divinorum. Total synthesis efforts have delivered multiple, orthogonal routes to salvinorin A, its congeners and related analogs with the goal of optimizing its activity towards multiple functional endpoints. Here we review total syntheses of the salvinorin chemotype and discuss outstanding problems that synthesis can address in the future.
摘要
涵盖
2000 年至 2020 年 致幻二萜化合物 salvinorin A 强效且选择性地激动人类 κ-阿片受体（KOR）。其独特属性——缺乏碱性氮原子、快速穿透大脑、半衰期短——再加上 KOR 作为新兴的镇痛药靶点的潜力，刺激了基于 Salvia divinorum 提取物的半合成的广泛药物化学研究。全合成工作已经提供了多种、正交的路线来合成 salvinorin A、其同系物和相关类似物，目的是优化其对多个功能终点的活性。本文我们综述了 salvinorin 类化合物的全合成，并讨论了合成在未来可以解决的突出问题。
相似文献
1
Chemical syntheses of the salvinorin chemotype of KOR agonist.KOR 激动剂中 salvinorin 型的化学合成。
Nat Prod Rep. 2020 Nov 18;37(11):1478-1496. doi: 10.1039/d0np00028k.
2
A review of salvinorin analogs and their kappa-opioid receptor activity.萨尔维诺林类似物及其κ-阿片受体活性综述。
Bioorg Med Chem Lett. 2018 May 15;28(9):1436-1445. doi: 10.1016/j.bmcl.2018.03.029. Epub 2018 Mar 12.
3
A unique natural selective kappa-opioid receptor agonist, salvinorin A, and its roles in human therapeutics.一种独特的天然选择性κ-阿片受体激动剂——Salvinorin A及其在人类治疗中的作用。
Phytochemistry. 2017 May;137:9-14. doi: 10.1016/j.phytochem.2017.02.001. Epub 2017 Feb 10.
4
Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations.Salvinorin A是致幻鼠尾草（Salvia divinorum）的一种活性成分，是一种高效的κ-阿片受体激动剂：结构与功能方面的考量。
J Pharmacol Exp Ther. 2004 Mar;308(3):1197-203. doi: 10.1124/jpet.103.059394. Epub 2004 Jan 8.
5
Kappa-opioid receptor-selective dicarboxylic ester-derived salvinorin A ligands.κ-阿片受体选择性二羧酸酯衍生萨维林 A 配体。
Bioorg Med Chem Lett. 2013 May 15;23(10):2860-2. doi: 10.1016/j.bmcl.2013.03.111. Epub 2013 Apr 4.
6
Ultrapotent effects of salvinorin A, a hallucinogenic compound from Salvia divinorum, on LPS-stimulated murine macrophages and its anti-inflammatory action in vivo.迷幻鼠尾草中致幻化合物 salvinorin A 的超强效作用对 LPS 刺激的小鼠巨噬细胞的影响及其体内抗炎作用。
J Mol Med (Berl). 2011 Sep;89(9):891-902. doi: 10.1007/s00109-011-0752-4. Epub 2011 Apr 16.
7
Synthesis and κ-opioid receptor activity of furan-substituted salvinorin A analogues.呋喃取代的鼠尾草酚A类似物的合成及κ-阿片受体活性
J Med Chem. 2014 Dec 26;57(24):10464-75. doi: 10.1021/jm501521d. Epub 2014 Dec 9.
8
Inhibitory effect of salvinorin A, from Salvia divinorum, on ileitis-induced hypermotility: cross-talk between kappa-opioid and cannabinoid CB(1) receptors.来自鼠尾草的鼠尾草酸对回肠炎诱导的运动亢进的抑制作用：κ-阿片受体与大麻素CB(1)受体之间的相互作用
Br J Pharmacol. 2008 Nov;155(5):681-9. doi: 10.1038/bjp.2008.294. Epub 2008 Jul 14.
9
Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist.Salvinorin A：一种强效的天然非含氮κ阿片受体选择性激动剂。
Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11934-9. doi: 10.1073/pnas.182234399. Epub 2002 Aug 21.
10
O6C-20-nor-salvinorin A is a stable and potent KOR agonist.O6C - 20 - 去甲 - 萨尔文诺林A是一种稳定且强效的κ阿片受体激动剂。
Bioorg Med Chem Lett. 2018 Sep 1;28(16):2770-2772. doi: 10.1016/j.bmcl.2018.01.055. Epub 2018 Jan 31.
引用本文的文献
1
Salvinorin A and : Toxicology, Pharmacological Profile, and Therapeutic Potential.沙维诺林A与：毒理学、药理学特征及治疗潜力
Int J Mol Sci. 2025 Jun 11;26(12):5588. doi: 10.3390/ijms26125588.
2
Function-Oriented Synthesis of Pentacyclic Triterpenoids and Discovery of an -Estrane as a Natural Product-Inspired Androgen Receptor Antagonist.五环三萜类化合物的功能导向合成及 - 雄烷类作为天然产物灵感的雄激素受体拮抗剂的发现。
Org Lett. 2024 Apr 19;26(15):3054-3059. doi: 10.1021/acs.orglett.4c00697. Epub 2024 Apr 1.
3
A Route to Potent, Selective, and Biased Salvinorin Chemical Space.通往强效、选择性和偏向性鼠尾草酸化学空间的途径。
ACS Cent Sci. 2023 Jul 12;9(8):1567-1574. doi: 10.1021/acscentsci.3c00616. eCollection 2023 Aug 23.
4
Salvaging Salvinorin: From Hallucinogen to Potential Therapeutic through Chemical Synthesis.挽救鼠尾草碱：从致幻剂到通过化学合成实现潜在治疗用途
ACS Cent Sci. 2023 Aug 10;9(8):1522-1524. doi: 10.1021/acscentsci.3c00955. eCollection 2023 Aug 23.
5
Asymmetric Syntheses of (+)- and (-)-Collybolide Enable Reevaluation of -Opioid Receptor Agonism.（+）-和（-）-棒盘孢菌素的不对称合成助力对μ-阿片受体激动作用的重新评估。
ACS Cent Sci. 2022 Jul 27;8(7):948-954. doi: 10.1021/acscentsci.2c00442. Epub 2022 Jul 18.
6
Formal Total Synthesis of Salvinorin A.萨尔瓦林 A 的全合成。
ChemistryOpen. 2022 Oct;11(10):e202200015. doi: 10.1002/open.202200015. Epub 2022 Feb 26.
7
A Protecting-Group-Free Synthesis of (-)-Salvinorin A.无保护基合成（-）-萨尔瓦林 A
Chemistry. 2021 May 20;27(29):7968-7973. doi: 10.1002/chem.202100560. Epub 2021 May 2.
8
Natural Product Synthesis through the Lens of Informatics.通过信息学视角看天然产物合成。
Acc Chem Res. 2021 Mar 2;54(5):1157-1167. doi: 10.1021/acs.accounts.0c00791. Epub 2021 Feb 12.
9
Pharmacokinetics and Pharmacodynamics of Salvinorin A and : Clinical and Forensic Aspects.鼠尾草叶大麻酚A的药代动力学与药效学：临床与法医学方面
Pharmaceuticals (Basel). 2021 Feb 3;14(2):116. doi: 10.3390/ph14020116.
本文引用的文献
1
Synthetic, Mechanistic, and Biological Interrogation of Chemical Space En Route to (-)-Bilobalide.合成、机械和生物学探究(-)-银杏内酯的化学空间。
J Am Chem Soc. 2020 Oct 28;142(43):18599-18618. doi: 10.1021/jacs.0c08231. Epub 2020 Oct 16.
2
A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus.一项针对血液透析瘙痒患者的非那雄胺的 3 期临床试验。
N Engl J Med. 2020 Jan 16;382(3):222-232. doi: 10.1056/NEJMoa1912770. Epub 2019 Nov 8.
3
Cutting-Edge Search for Safer Opioid Pain Relief: Retrospective Review of Salvinorin A and Its Analogs.寻找更安全阿片类药物止痛方法的前沿探索：对Salvinorin A及其类似物的回顾性研究
Front Psychiatry. 2019 Mar 27;10:157. doi: 10.3389/fpsyt.2019.00157. eCollection 2019.
4
Intermolecular Heck Coupling with Hindered Alkenes Directed by Potassium Carboxylates.受阻烯烃的钾羧酸盐导向的分子间 Heck 偶联。
Angew Chem Int Ed Engl. 2019 Feb 18;58(8):2371-2376. doi: 10.1002/anie.201813233. Epub 2019 Jan 25.
5
Kappa Opioid Receptor Agonist Mesyl Sal B Attenuates Behavioral Sensitization to Cocaine with Fewer Aversive Side-Effects than Salvinorin A in Rodents.κ 阿片受体激动剂甲磺酰基萨布素 B 比沙蒽酮 A 更能减轻可卡因引起的行为敏化，且不良反应更少。
Molecules. 2018 Oct 11;23(10):2602. doi: 10.3390/molecules23102602.
6
Untangling the complexity of opioid receptor function.解析阿片受体功能的复杂性。
Neuropsychopharmacology. 2018 Dec;43(13):2514-2520. doi: 10.1038/s41386-018-0225-3. Epub 2018 Sep 24.
7
Total Synthesis of the Neoclerodane Diterpene Salvinorin A via an Intramolecular Diels-Alder Strategy.通过分子内 Diels-Alder 策略全合成新穿心莲烷二萜 Salvinorin A。
Org Lett. 2018 Jun 1;20(11):3418-3421. doi: 10.1021/acs.orglett.8b01357. Epub 2018 May 22.
8
A review of salvinorin analogs and their kappa-opioid receptor activity.萨尔维诺林类似物及其κ-阿片受体活性综述。
Bioorg Med Chem Lett. 2018 May 15;28(9):1436-1445. doi: 10.1016/j.bmcl.2018.03.029. Epub 2018 Mar 12.
9
O6C-20-nor-salvinorin A is a stable and potent KOR agonist.O6C - 20 - 去甲 - 萨尔文诺林A是一种稳定且强效的κ阿片受体激动剂。
Bioorg Med Chem Lett. 2018 Sep 1;28(16):2770-2772. doi: 10.1016/j.bmcl.2018.01.055. Epub 2018 Jan 31.
10
Structure of the Nanobody-Stabilized Active State of the Kappa Opioid Receptor.纳米抗体稳定的κ阿片受体活性状态结构。
Cell. 2018 Jan 11;172(1-2):55-67.e15. doi: 10.1016/j.cell.2017.12.011. Epub 2018 Jan 4.
Zotero 插件