Synthesis of 24(S)-hydroxycholesterol esters responsible for the induction of neuronal cell death.
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.
Tokyo New Drug Research Laboratories, Pharmaceutical Division, Kowa Co., Ltd, 2-17-43, Noguchicho, Higashimurayama, Tokyo 189-0022, Japan. Electronic address: k-sibuya@kowa.co.jp.
Kimiyuki
K
Shibuya
Tokyo New Drug Research Laboratories, Pharmaceutical Division, Kowa Co., Ltd, 2-17-43, Noguchicho, Higashimurayama, Tokyo 189-0022, Japan.
Toshiaki
T
Watanabe
Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, 1-3 Miyakodani, Tatara, Kyotanabe, Kyoto 610-0394, Japan.
Yasuomi
Y
Urano
Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, 1-3 Miyakodani, Tatara, Kyotanabe, Kyoto 610-0394, Japan.
Wakako
W
Takabe
Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, 1-3 Miyakodani, Tatara, Kyotanabe, Kyoto 610-0394, Japan.
Noriko
N
Noguchi
Department of Molecular Chemistry and Biochemistry, Faculty of Sciences and Technology, Doshisha University, 1-3 Miyakodani, Tatara, Kyotanabe, Kyoto 610-0394, Japan.
Hiroaki
H
Kitagishi
D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006888:Hydroxycholesterols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D006888:Hydroxycholesterols
24(S)-Hydroxycholesterol; 24(S)-Hydroxycholesterol ester; Acyl-CoA:cholesterol acyltransferase-1; Neuronal cell death; Unsaturated long-chain fatty acids