通过一种生成Z-烯酰胺的新反应实现TMC-95A和-B的全合成。关于构效关系的一些初步发现。
Total synthesis of TMC-95A and -B via a new reaction leading to Z-enamides. Some preliminary findings as to SAR.
作者信息
Lin Songnian, Yang Zhi-Qiang, Kwok Benjamin H B, Koldobskiy Michael, Crews Craig M, Danishefsky Samuel J
机构信息
Laboratory for Bioorganic Chemistry, Sloan Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, USA.
出版信息
J Am Chem Soc. 2004 May 26;126(20):6347-55. doi: 10.1021/ja049821k.
Abstract
A full account of the total syntheses of proteasome inhibitors TMC-95A and -B is provided. A key feature of the syntheses involved installation of a cis-propenylamide moiety by a thermal rearrangement of an alpha-silylallyl amide. The scope and mechanism of the enamide-forming reaction are discussed. Also provided are some preliminary results from SAR studies. It was found that simplified analogues can retain the full potency of proteasome inhibition.
摘要
本文全面介绍了蛋白酶体抑制剂TMC-95A和TMC-95B的全合成。这些合成的一个关键特征是通过α-硅烷基烯丙基酰胺的热重排来安装顺式丙烯酰胺部分。讨论了烯酰胺形成反应的范围和机理。还提供了一些构效关系（SAR）研究的初步结果。发现简化的类似物可以保留蛋白酶体抑制的全部效力。
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Total synthesis of TMC-95A and -B via a new reaction leading to Z-enamides. Some preliminary findings as to SAR.通过一种生成Z-烯酰胺的新反应实现TMC-95A和-B的全合成。关于构效关系的一些初步发现。
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本文引用的文献
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Total synthesis of TMC-95A.TMC-95A的全合成。
Angew Chem Int Ed Engl. 2003 Jun 16;42(23):2654-7. doi: 10.1002/anie.200351130.
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Simplified synthetic TMC-95A/B analogues retain the potency of proteasome inhibitory activity.简化的合成TMC-95A/B类似物保留了蛋白酶体抑制活性的效力。
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Mechanism of cis-enamide formation from N-(alpha-silyl)allyl amides: synthetic potential of stepwise dyotropic rearrangements.由N-（α-硅基）烯丙基酰胺形成顺式烯酰胺的机理：逐步双变性重排的合成潜力。
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A concise formal total synthesis of TMC-95A/B proteasome inhibitors.TMC-95A/B蛋白酶体抑制剂的简洁形式全合成。
Org Lett. 2003 Jan 23;5(2):197-200. doi: 10.1021/ol0272545.
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The total synthesis of proteasome inhibitors TMC-95A and TMC-95B: discovery of a new method to generate cis-propenyl amides.蛋白酶体抑制剂TMC-95A和TMC-95B的全合成：一种生成顺式丙烯酰胺的新方法的发现。
Angew Chem Int Ed Engl. 2002 Feb 1;41(3):512-5. doi: 10.1002/1521-3773(20020201)41:3<512::aid-anie512>3.0.co;2-r.
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Not just research tools--proteasome inhibitors offer therapeutic promise.蛋白酶体抑制剂不仅是研究工具，还具有治疗前景。
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Stereocontrolled synthesis of the northern part of potent proteasome inhibitor TMC-95A.强效蛋白酶体抑制剂TMC-95A北部的立体控制合成。
Org Lett. 2001 Sep 6;3(18):2863-5. doi: 10.1021/ol016303v.
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Proteasome inhibitors: from research tools to drug candidates.蛋白酶体抑制剂：从研究工具到候选药物
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Crystal structure of the 20 S proteasome:TMC-95A complex: a non-covalent proteasome inhibitor.20S蛋白酶体与TMC-95A复合物的晶体结构：一种非共价蛋白酶体抑制剂
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