Three‐Component, One‐Pot Tandem Sonogashira/Suzuki‐Miyaura Coupling Reactions for the Synthesis of a Library of Ceramide‐Transport Protein Inhibitors Designed in Silico,Asian Journal of Organic Chemistry

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Three‐Component, One‐Pot Tandem Sonogashira/Suzuki‐Miyaura Coupling Reactions for the Synthesis of a Library of Ceramide‐Transport Protein Inhibitors Designed in Silico
Asian Journal of Organic Chemistry ( IF 2.8 ) Pub Date : 2020-01-24 , DOI: 10.1002/ajoc.201900689
Masaharu Ueno _{1,

2} , Norikazu Miyoshi ₂ , Kentaro Hanada ₃ , Shū Kobayashi ₁

Affiliation

We have developed a one‐pot, tandem Sonogashira/Suzuki‐Miyaura coupling reaction, which was unknown synthetically, and applied it for the synthesis of a library of potential natural ligand nonmimetic inhibitors of the lipid‐transfer protein, ceramide‐transport protein (CERT). The characteristic feature of this reaction is that the two‐step coupling reaction proceeds smoothly with only 5 mol% of palladium catalyst. Furthermore, the location of the formed carbon−carbon bond would be strictly defined because of the difference in reactivity. Therefore, many derivatives could be synthesized in high yields without the formation of regioisomeric byproducts by the same procedure. We also performed a semi‐gram scale synthesis of several derivatives to provide the bioactive assay. After synthesizing as many as 113 derivatives, we identified a non‐natural mimetic inhibitor with activity comparable to that of the known inhibitor (1R,3S)‐HPA‐12.

中文翻译：

三组分一锅串联Sonogashira / Suzuki-Miyaura偶联反应，用于合成由硅胶设计的神经酰胺转运蛋白抑制剂库

我们开发了一种单串联串联的Sonogashira / Suzuki-Miyaura偶联反应，该反应在合成上尚不为人所知，并将其用于合成脂质转移蛋白，神经酰胺转运蛋白（CERT）的潜在天然配体非模拟抑制剂文库）。该反应的特征是，仅用5mol％的钯催化剂，两步偶联反应顺利进行。此外，由于反应性的差异，将严格定义形成的碳-碳键的位置。因此，可以通过相同的方法以高收率合成许多衍生物而不会形成区域异构副产物。我们还对几种衍生物进行了半克级合成，以提供生物活性测定。合成了多达113个衍生物之后，R，3 S）-HPA-12。

更新日期：2020-01-24

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