Synthesis of 24(S)-hydroxycholesterol esters responsible for the induction of neuronal cell death.
Synthesis of 24(S)-hydroxycholesterol esters responsible for the induction of neuronal cell death.
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DOI：
10.1016/j.bmc.2016.04.024
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发表时间：
2016-06
影响因子：
3.5
通讯作者：
K. Shibuya;Toshiaki Watanabe;Yasuomi Urano;Wakako Takabe;N. Noguchi;Hiroaki Kitagishi
中科院分区：
文献类型：
--
作者：
K. Shibuya;Toshiaki Watanabe;Yasuomi Urano;Wakako Takabe;N. Noguchi;Hiroaki Kitagishi
我们通过酰基辅酶A：胆固醇酰基转移酶-1 (ACAT-1) 的催化，合成了几种参与神经元细胞死亡的候选 24(S)-羟基胆固醇 (24S-OHC) 酯。我们研究了仲醇在 24S-OHC 3 位或 24 位酰化的区域选择性。将适当的饱和和不饱和长链脂肪酸用受保护的24S-OHC酯化，然后脱保护，以令人满意的产率提供所需的酯。然后，我们通过 HPLC 监测证实，24S-OHC 的四种酯（即 3-油酸酯、3-亚油酸酯、3-花生四烯酸酯和 3-二十二碳六烯酸酯）的保留时间与在 24S-OHC 处理的 SH-SY5Y 细胞中观察到的 24S-OHC 酯的保留时间一致。
We synthesized several candidates of 24(S)-hydroxycholesterol (24S-OHC) esters, which are involved in neuronal cell death, through catalysis with acyl-CoA:cholesterol acyltransferase-1 (ACAT-1). We studied the regioselectivity of the acylation of the secondary alcohol at the 3- or 24-position of 24S-OHC. The appropriate saturated and unsaturated long-chain fatty acids were esterified with the protected 24S-OHC and then de-protected to afford the desired esters at a satisfactory yield. We then confirmed by HPLC monitoring that the retention times of four esters of 24S-OHC, namely 3-oleate, 3-linoleate, 3-arachidonoate and 3-docosahexaenoate, were consistent with those of 24S-OHC esters observed in 24S-OHC-treated SH-SY5Y cells.