Minimal Fluorous Tagging Strategy that Enables the Synthesis of the Complete Stereoisomer Library of SCH725674 Macrolactones

Four mixtures of four fluorous-tagged quasiisomers have been synthesized, demixed, and detagged to make all 16 stereoisomers of the macrocyclic lactone natural product Sch725674. A new bare-minimum tagging pattern needs only two tagsone fluorous and one nonfluorousto encode four isomers. The structure of Sch725674 is assigned as (5<i>R</i>,6<i>S</i>,8<i>R</i>,14<i>R</i>,<i>E</i>)-5,6,8-trihydroxy-14-pentyloxacyclotetradec-3-en-2-one. Various comparisons of spectra of 32 lactones (16 with tags, 16 without) and 16 ester precursors (8 with tags, 8 without) provide insights into when and why related compounds have the same or different spectra