α-1C-半乳糖基神经酰胺的全合成，一种免疫刺激的 C-糖鞘脂，以及第一代合成中立体化学的确认。
Total synthesis of α-1C-galactosylceramide, an immunostimulatory C-glycosphingolipid, and confirmation of the stereochemistry in the first-generation synthesis.
机构信息
Department of Chemistry and Biochemistry, Queens College of The City University of New York, Flushing, New York 11367-1597, United States.
出版信息
J Org Chem. 2011 Nov 4;76(21):8588-98. doi: 10.1021/jo201450s. Epub 2011 Oct 4.
Abstract
A nonisosteric α-C-glycoside analogue of KRN7000 (α-1C-GalCer, 1) was reported to induce a selective type of cytokine release in human invariant natural killer cells in vitro. We report here a very concise synthetic route to 1 and its analogue 1'. The key steps include olefin cross-metathesis, Sharpless asymmetric epoxidation, and epoxide opening by NaN(3)/NH(4)Cl. Inversion of configuration at the amide-bearing carbon in the phytosphingosine backbone constructed by epoxide opening in our previous synthesis of 1 was verified, indicating that remote group participation is not involved during the epoxide-opening reaction.
摘要
一种非同系的 α-C-糖苷类似物 KRN7000（α-1C-GalCer，1）被报道在体外能诱导人类不变自然杀伤细胞选择性地释放细胞因子。我们在此报告了一种非常简洁的 1 及其类似物 1'的合成路线。关键步骤包括烯烃交叉复分解、Sharpless 不对称环氧化以及通过NaN(3)/NH(4)Cl 开环。我们之前合成 1 时通过环氧化开环构建的植烷醇骨架中酰胺碳的构型翻转得到了验证，表明在开环反应过程中没有远程基团参与。
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