Total Syntheses of Four Metabolites of 15‐F2t‐Isoprostane

Total syntheses are described of the methyl esters of enantiomers of two major urinary metabolites of 15F2t-isoprostane − 2,3-dinor-5,6-dihydro-15F2t-isoprostane 1 and 2,3-dinor-15F2t-isoprostane 2 − together with other, related, putative metabolites (15R)/(15S)-2,3-dinor-5,6,13,14-tetrahydro-15F2t-isoprostane 3 and 2,3-dinor-5,6,13,14-tetrahydro-15-oxo-15F2t-isoprostane 4. The synthesis, starting from diacetone D-glucose, includes as its main steps a radical cyclization reaction of highly functionalized precursors, followed by Wittig and/or Horner−Wadsworth−Emmons elongation using phosphorus synthons. The compounds synthesized here have been used as reference compounds for studying the metabolism of 15F2t-isoprostane and ent-15F2t-isoprostane.