• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

马当胺类化合物：合成结构复杂生物碱的策略

The Madangamines: Synthetic Strategies Toward Architecturally Complex Alkaloids.

作者信息

Ríos Valentina, Maulen Cristian, Parra Claudio, Bradshaw Ben

机构信息

Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad de Concepción, Concepción 4070371, Chile.

Laboratori de Química Organica, Facultat de Farmacia, IBUB, Universitat de Barcelona, 08028 Barcelona, Spain.

出版信息

Mar Drugs. 2025 Jul 28;23(8):301. doi: 10.3390/md23080301.

DOI:10.3390/md23080301
PMID:40863618
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12387135/
Abstract

Madangamine alkaloids have attracted considerable interest in the scientific community due to their complex polycyclic structures and potent biological activities. The six members identified to date have exhibited diverse and significant cytotoxic activities against various cancer cell lines. Despite their structural complexity, seven total syntheses-covering five of the six members-have been reported to date. These syntheses, involving 28 to 36 steps and global yields ranging from 0.006% to 0.029%, highlight the formidable challenge these compounds present. This review summarizes the key synthetic strategies developed to access critical fragments, including the construction of the ABC diazatricyclic core and the ACE ring systems. Approaches to assembling the ABCD and ABCE tetracyclic frameworks are also discussed. Finally, we highlight the completed total syntheses of madangamines A-E, with a focus on pivotal transformations and strategic innovations that have enabled progress in this field.

摘要

马达加明生物碱因其复杂的多环结构和强大的生物活性而在科学界引起了相当大的关注。迄今为止鉴定出的六个成员已对各种癌细胞系表现出多样且显著的细胞毒性活性。尽管其结构复杂，但迄今为止已报道了七种全合成方法，涵盖六个成员中的五个。这些合成方法涉及28至36步，总产率在0.006%至0.029%之间，凸显了这些化合物所带来的巨大挑战。本综述总结了为获取关键片段而开发的关键合成策略，包括构建ABC二氮杂三环核心和ACE环系统。还讨论了组装ABCD和ABCE四环骨架的方法。最后，我们重点介绍了马达加明A - E的全合成，着重于关键转化和战略创新，这些推动了该领域的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/98505e296934/marinedrugs-23-00301-sch020.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/69169d0f4199/marinedrugs-23-00301-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/4de050ace0a3/marinedrugs-23-00301-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/7f91b6a023b8/marinedrugs-23-00301-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/444fdde53a32/marinedrugs-23-00301-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/0cdce4b95fff/marinedrugs-23-00301-sch003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/9955579846fb/marinedrugs-23-00301-sch004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/95fcc50fb4fd/marinedrugs-23-00301-sch005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/a73fa35e1b31/marinedrugs-23-00301-sch006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/efae72c9d201/marinedrugs-23-00301-sch007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/1cdafc95ea6b/marinedrugs-23-00301-sch008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/1f8c5000503b/marinedrugs-23-00301-sch009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/c515baba7537/marinedrugs-23-00301-sch010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/093cf341e199/marinedrugs-23-00301-sch011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/f842bed69084/marinedrugs-23-00301-sch012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/5e5f71ed0dc0/marinedrugs-23-00301-sch013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/99b311034a82/marinedrugs-23-00301-sch014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/98ea1424b9ee/marinedrugs-23-00301-sch015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/204821d00054/marinedrugs-23-00301-sch016.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/0e93585d7494/marinedrugs-23-00301-sch017.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/453725242c14/marinedrugs-23-00301-sch018.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/a6f8c9a5ad98/marinedrugs-23-00301-sch019.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/98505e296934/marinedrugs-23-00301-sch020.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/69169d0f4199/marinedrugs-23-00301-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/4de050ace0a3/marinedrugs-23-00301-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/7f91b6a023b8/marinedrugs-23-00301-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/444fdde53a32/marinedrugs-23-00301-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/0cdce4b95fff/marinedrugs-23-00301-sch003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/9955579846fb/marinedrugs-23-00301-sch004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/95fcc50fb4fd/marinedrugs-23-00301-sch005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/a73fa35e1b31/marinedrugs-23-00301-sch006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/efae72c9d201/marinedrugs-23-00301-sch007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/1cdafc95ea6b/marinedrugs-23-00301-sch008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/1f8c5000503b/marinedrugs-23-00301-sch009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/c515baba7537/marinedrugs-23-00301-sch010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/093cf341e199/marinedrugs-23-00301-sch011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/f842bed69084/marinedrugs-23-00301-sch012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/5e5f71ed0dc0/marinedrugs-23-00301-sch013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/99b311034a82/marinedrugs-23-00301-sch014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/98ea1424b9ee/marinedrugs-23-00301-sch015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/204821d00054/marinedrugs-23-00301-sch016.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/0e93585d7494/marinedrugs-23-00301-sch017.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/453725242c14/marinedrugs-23-00301-sch018.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/a6f8c9a5ad98/marinedrugs-23-00301-sch019.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d78/12387135/98505e296934/marinedrugs-23-00301-sch020.jpg

相似文献

1
The Madangamines: Synthetic Strategies Toward Architecturally Complex Alkaloids.马当胺类化合物：合成结构复杂生物碱的策略
Mar Drugs. 2025 Jul 28;23(8):301. doi: 10.3390/md23080301.
2
Divergent Synthesis of and Structurally Related Monoterpenoid Indole Alkaloids: A Non-biomimetic Strategy.与结构相关的单萜吲哚生物碱的发散合成：一种非仿生策略。
Acc Chem Res. 2025 Sep 2;58(17):2781-2791. doi: 10.1021/acs.accounts.5c00461. Epub 2025 Aug 21.
3
The alkaloids of the madangamine group.马丹胺类生物碱。
Alkaloids Chem Biol. 2015;74:159-99. doi: 10.1016/bs.alkal.2014.10.001.
4
Prescription of Controlled Substances: Benefits and Risks管制药品的处方：益处与风险
5
Isolation, biological activity, and synthesis of isoquinoline alkaloids.异喹啉生物碱的分离、生物活性及合成。
Nat Prod Rep. 2024 Nov 13;41(11):1652-1722. doi: 10.1039/d4np00023d.
6
Discovery of a potent C-oxime pachysandra alkaloid analogue promising for treatment of hepatocellular carcinoma.发现一种有望用于治疗肝细胞癌的强效碳肟型富贵草生物碱类似物。
Bioorg Med Chem. 2025 Nov 1;129:118324. doi: 10.1016/j.bmc.2025.118324. Epub 2025 Jul 19.
7
Guanidine alkaloids from marine sponges.来自海洋海绵的胍生物碱。
Alkaloids Chem Biol. 2025;94:1-101. doi: 10.1016/bs.alkal.2025.06.001. Epub 2025 Jul 16.
8
Verticillins: fungal epipolythiodioxopiperazine alkaloids with chemotherapeutic potential.青枯菌素：具有化疗潜力的真菌表二氧杂环戊烯基哌嗪类生物碱。
Nat Prod Rep. 2024 Sep 18;41(9):1327-1345. doi: 10.1039/d3np00068k.
9
The chemistry and biology of pyrazole and indazole alkaloids.吡唑和吲唑生物碱的化学与生物学
Alkaloids Chem Biol. 2025;94:103-156. doi: 10.1016/bs.alkal.2025.03.001. Epub 2025 May 28.
10
Updates on Intrinsic Medicinal Chemistry of 1,4-dihydropyridines, Perspectives on Synthesis and Pharmacokinetics of Novel 1,4-dihydropyrimidines as Calcium Channel Blockers: Clinical Pharmacology.1,4 - 二氢吡啶的内在药物化学进展，新型1,4 - 二氢嘧啶作为钙通道阻滞剂的合成与药代动力学展望：临床药理学
Curr Top Med Chem. 2025 Jan 1. doi: 10.2174/0115680266323908241114064318.

本文引用的文献

1
A New Organocatalytic Desymmetrization Reaction Enables the Enantioselective Total Synthesis of Madangamine E.一种新的有机催化去对称化反应能够实现 Madangamine E 的对映选择性全合成。
J Am Chem Soc. 2022 Jan 26;144(3):1407-1415. doi: 10.1021/jacs.1c12040. Epub 2022 Jan 17.
2
Identification of madangamine A as a novel lysosomotropic agent to inhibit autophagy.鉴定马丹胺A为一种新型溶酶体亲和剂以抑制自噬。
Bioorg Med Chem. 2021 Mar 15;34:116041. doi: 10.1016/j.bmc.2021.116041. Epub 2021 Jan 27.
3
Access to Enantiopure Advanced Intermediates en Route to Madangamines.
手性纯的高级中间体在通往马当加宁路线上的应用。
Chemistry. 2019 Dec 10;25(69):15929-15933. doi: 10.1002/chem.201904045. Epub 2019 Nov 12.
4
Synthesis of the Madangamine Alkaloid Core by a C-C Bond Activation Cascade.通过 C-C 键活化级联反应合成马当胺生物碱核心。
Org Lett. 2019 Aug 2;21(15):6149-6154. doi: 10.1021/acs.orglett.9b02331. Epub 2019 Jul 24.
5
Enantioselective formal synthesis of (+)-madangamine A.
Chem Commun (Camb). 2019 Jun 25;55(50):7207-7210. doi: 10.1039/c9cc03690c. Epub 2019 Jun 5.
6
Oxamidation of Unsaturated O-Alkyl Hydroxamates: Synthesis of the Madangamine Diazatricylic (ABC Rings) Skeleton.不饱和 O-烷氧基羟胺的氧化酰胺化：马当胺二氮三环（ABC 环）骨架的合成。
Org Lett. 2017 Dec 15;19(24):6570-6573. doi: 10.1021/acs.orglett.7b03283. Epub 2017 Nov 28.
7
Unified Total Synthesis of Madangamines A, C, and E.芒当加胺 A、C 和 E 的全合成
J Am Chem Soc. 2017 Mar 1;139(8):2952-2955. doi: 10.1021/jacs.7b00807. Epub 2017 Feb 16.
8
The alkaloids of the madangamine group.马丹胺类生物碱。
Alkaloids Chem Biol. 2015;74:159-99. doi: 10.1016/bs.alkal.2014.10.001.
9
Synthesis of the tetracyclic ABCD ring systems of madangamines D-F.合成马当胺 D-F 的四环 ABCD 环系。
Org Lett. 2015 Feb 6;17(3):568-71. doi: 10.1021/ol503586d. Epub 2015 Jan 21.
10
Total synthesis of (+)-madangamine D.（+）-马当胺 D 的全合成。
Angew Chem Int Ed Engl. 2014 Jun 10;53(24):6202-5. doi: 10.1002/anie.201402263. Epub 2014 May 2.