Synthesis of a fluorinated analogue of anticancer active ether lipids.
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.
Burchardt
A
A
Organisch-Chemisches Institut, Westfälische Wilhelms-Universität, Corrensstrasse 40, D-48149 Münster, Germany.
Takahashi
T
T
Takeuchi
Y
Y
Haufe
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004987:Ethers / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry*; D008055:Lipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D013057:Spectrum Analysis; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004987:Ethers; D008055:Lipids; D005461:Fluorine