埃博霉素B（Et-743）的合成研究。五环核心的组装及形式上的全合成。
Synthetic studies on Et-743. Assembly of the pentacyclic core and a formal total synthesis.
作者信息
Fishlock Dan, Williams Robert M
机构信息
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, USA.
出版信息
J Org Chem. 2008 Dec 19;73(24):9594-600. doi: 10.1021/jo801159k.
Abstract
A formal total synthesis of the potent anticancer agent Et-743 is described. The tetrahydroisoquinoline core is stereoselectively constructed using a novel radical cyclization of a glyoxalimine. Further elaboration of this core rapidly accessed the pentacyclic core of Et-743, but a mixture of regiosisomers was obtained in the key Pictet-Spengler ring closure. A known advanced intermediate in the synthesis of Et-743 was intercepted, constituting a formal synthesis of the molecule.
摘要
本文描述了强效抗癌药物Et-743的正式全合成。使用乙二醛亚胺的新型自由基环化反应立体选择性地构建了四氢异喹啉核心。对该核心的进一步修饰能够快速得到Et-743的五环核心，但在关键的Pictet-Spengler环合反应中得到了区域异构体的混合物。截获了Et-743合成中一个已知的高级中间体，完成了该分子的形式合成。
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本文引用的文献
1
Total Synthesis of (-)-Tetrazomine and Determination of Its Stereochemistry.
Angew Chem Int Ed Engl. 2001 Apr 17;40(8):1463-1465. doi: 10.1002/1521-3773(20010417)40:8<1463::AID-ANIE1463>3.0.CO;2-8.
2
Regioselectivity of Pictet-Spengler Cyclization Reactions to Construct the Pentacyclic Frameworks of the Ecteinascidin-Saframycin Class of Tetrahydroisoquinoline Antitumor Antibiotics.
Tetrahedron Lett. 2007 May 21;48(21):3719-3722. doi: 10.1016/j.tetlet.2007.03.113.
3
Total synthesis of the marine natural product (-)-cribrostatin 4 (renieramycin H).
Angew Chem Int Ed Engl. 2007;46(21):3962-5. doi: 10.1002/anie.200700539.
4
Asymmetric total synthesis of (-)-cribrostatin 4 (renieramycin H).
Angew Chem Int Ed Engl. 2007;46(9):1517-20. doi: 10.1002/anie.200604126.
5
Synthetic studies on Et-743. Asymmetric, stereocontrolled construction of the tetrahydroisoquinoline core via radical cyclization on a glyoxalimine.
Org Lett. 2006 Jul 20;8(15):3299-301. doi: 10.1021/ol061192r.
6
Antitumor activity of tetrahydroisoquinoline analogues 3-epi-jorumycin and 3-epi-renieramycin G.
Bioorg Med Chem Lett. 2006 Jun 15;16(12):3180-3. doi: 10.1016/j.bmcl.2006.03.042. Epub 2006 May 2.
7
Stereospecific formal total synthesis of ecteinascidin 743.
Angew Chem Int Ed Engl. 2006 Mar 3;45(11):1754-9. doi: 10.1002/anie.200503983.
8
Total synthesis of ecteinascidin 743.
J Am Chem Soc. 2006 Jan 11;128(1):87-9. doi: 10.1021/ja0571794.
9
Asymmetric total syntheses of (-)-jorumycin, (-)-renieramycin G, 3-epi-jorumycin, and 3-epi-renieramycin G.
J Am Chem Soc. 2005 Sep 14;127(36):12684-90. doi: 10.1021/ja0535918.
10
Synthetic studies toward ecteinascidin 743.
J Org Chem. 2005 May 27;70(11):4397-408. doi: 10.1021/jo050408k.
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