Synthesis of a fluorinated analogue of anticancer active ether lipids

被引:25
作者
Burchardt, A
Takahashi, T
Takeuchi, Y
Haufe, G
机构
[1] Univ Munster, Inst Organ Chem, D-48149 Munster, Germany
[2] Toyama Med & Pharmaceut Univ, Toyama 9300194, Japan
关键词
D O I
10.1021/jo0016172
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
The synthesis of racemic 2 '- (trimethylammonium)ethyl-3-hexadecyloxy-2-fluoro-2-(methoxymethyl)-prop-1-yl-phosphate (6), a fluorinated analogue of an anticancer active ether Lipid 5 was realized with 3% overall yield in a nine-step synthesis starting from 2-methylene-1,3-propanediol (7) using a bromofluorination as the key step. Both enantiomers of the precursor 8 of the ether lipid 6 were synthesized by lipase-catalyzed desymmetrization of the diacetate 17, either by hydrolysis (83% ee) or by lipase-catalyzed acetylation of the diol 22 (82% ee). The antitumor activity of 6 has been found in an in vivo model of the methylcholanthrene-induced fibrosarcoma of mice.
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页码:2078 / 2084
页数:7
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