合成路线1

Attachment of the CD-ring synthon to the solid-phase support required the introduction of an appropriate spacer group. Coupling between methyl 4-hydroxybenzenesulfonate (LIX) and the tetrahydropyranyl-protected diol (LX) under Mitsunobu conditions afforded the alkoxy sulfonate (LXI). The sulfonate ester of (LXI) was hydrolyzed with LiCl in refluxing acetone, and the resulting sulfonic acid was converted to sulfonyl chloride (LXII) by PCl5 -in DMF. Coupling of the CD-ring alcohol (LXIII) with the sulfonyl chloride (LXII), followed by acidic tetrahydropyranyl group cleavage gave the sulfonate linker-bound CD synthon (LXIV). This was attached to a previously chlorinated diethylsilyl resin to furnish the resin-bound CD ring (LXV). Alternatively, resin (LXV) was prepared by a more general method consisting in the initial attachment of the sulfonate linker (LXII) to the resin support, and then loading alcohol (LXIII) to the resultant sulfonyl chloride resin (LXVI). Horner-Wadsworth-Emmons condensation of the resin-bound ketone (LXV) with the lithiated phosphine oxide (LVIII) yielded the triene compound (LXVII). Cleavage of the sulfonate resin and simultaneous introduction of the side chain substitution was achieved by copper-catalyzed displacement of sulfonate resin (LXVII) with the Grignard reagent (LXVIII). The silyl protecting groups were finally cleaved by treatment with CSA in aqueous methanol