Synthesis of (9R)- and (9S)-10-fluorodecan-9-olide (fluoro-phoracantholide I) first lipase-catalyzed enantioselective esterification of β-fluoroalcohols

Abstract

Synthesis of both enantiomers of fluoro-phoracantholide I, namely (9 S )-10-fluorodecan-9-olide ( (9S)-(−)- 1 and (9 R )-10-fluorodecan-9-olide (9R)-(+)- 1 , has been achieved through lipase-catalyzed enantioselective acetylation of methyl 10-fluoro-9-hydroxydecanoate ( 2a ) with acetic anhydride in the presence of Lipase Amano PS ( Pseudomonas cepacia ). The higher homologue, methyl 11-fluoro-10-hydroxyundecanoate ( 2b ) has also been resolved. These enzymatic resolutions by acetylation of ω-fluoro-(ω-1)-hydroxyalkanoic acid esters of longchain fatty acids represent the first lipase-catalyzed enantioselective esterifications of β-fluoroalcohols. Synthesis of both enantiomers of Fluoro-Phoracantholide I ( 1 ) key-step: enantioselective acetylation of β-fluoroalcohols with acetic anhydride and lipase of Pseudomonas cepacia .