Flexible, polymer-supported synthesis of sphingosine derivatives provides ceramides with enhanced biological activity.
Flexible, polymer-supported synthesis of sphingosine derivatives provides ceramides with enhanced biological activity.
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DOI：
10.1016/j.bmc.2014.07.024
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发表时间：
2014-10
影响因子：
3.5
通讯作者：
Adeeb El‐Dahshan;Samer I. Al-Gharabli;S. Radetzki;T. Al‐Tel;Pradeep Kumar;J. Rademann
中科院分区：
文献类型：
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作者：
Adeeb El‐Dahshan;Samer I. Al-Gharabli;S. Radetzki;T. Al‐Tel;Pradeep Kumar;J. Rademann
提出了一种聚合物负载的合成鞘氨醇衍生物的方法，该方法是基于聚磷酰乙烯醋酸酯与fmoc保护的氨基酸的c-酰化反应。该方法通过脱保护-脱羧序列，然后进行e选择性Wittig烯烃裂解，实现了鞘氨醇尾部的灵活变化。以LiAlH(O-tBu)3为还原剂，对酮基进行非对映选择性还原，合成了d-红鞘氨醇类似物。研究了神经酰胺和酮类神经酰胺对3种癌细胞HEP G-2、PC-12和HL-60增殖的影响，发现含有芳鞘氨醇尾部的神经酰胺最具活性。
A polymer-supported route for the synthesis of sphingosine derivatives is presented based on the C-acylation of polymeric phosphoranylidene acetates with an Fmoc-protected amino acid. The approach enables the flexible variation of the sphingosine tail through a deprotection–decarboxylation sequence followed by E-selective Wittig olefination cleavage.d-Erythro-sphingosine analogs have been synthesized by diastereoselective reduction of the keto group employing LiAlH(O-tBu)3as reducing agent. The effect of ceramides and keto-ceramides on the proliferation of three cancer cell lines HEP G-2, PC-12 and HL-60 was investigated and a ceramide containing an aromatic sphingosine tail was identified as being most active.