Shibuya Kimiyuki, Watanabe Toshiaki, Urano Yasuomi, Takabe Wakako, Noguchi Noriko, Kitagishi Hiroaki
Tokyo New Drug Research Laboratories, Pharmaceutical Division, Kowa Co., Ltd, 2-17-43, Noguchicho, Higashimurayama, Tokyo 189-0022, Japan.
Tokyo New Drug Research Laboratories, Pharmaceutical Division, Kowa Co., Ltd, 2-17-43, Noguchicho, Higashimurayama, Tokyo 189-0022, Japan.
Bioorg Med Chem. 2016 Jun 1;24(11):2559-2566. doi: 10.1016/j.bmc.2016.04.024. Epub 2016 Apr 12.
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.
我们通过酰基辅酶A：胆固醇酰基转移酶-1（ACAT-1）催化合成了几种参与神经元细胞死亡的24（S）-羟基胆固醇（24S-OHC）酯候选物。我们研究了24S-OHC的3位或24位仲醇酰化的区域选择性。将合适的饱和和不饱和长链脂肪酸与受保护的24S-OHC酯化，然后脱保护，以令人满意的产率得到所需的酯。然后，我们通过HPLC监测确认，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。
