Syntheses of the four enantiomerically pure diastereomers of 5-F-2t-isoprostane (5-8) are described. The key step is the lipase-catalyzed chemo-enzymatic resolution of the racemic diol 40 to give the monoacetates 41 and 42. The enantiomerically pure diastereomers of 5-F-2t-isoprostane (5) may be human hormones.