合成路线1

The cyclization of 1-(benzyloxy)butadiene (I) with silylated propargyl aldehyde (II) by means of a chiral chromium catalyst gives the chiral dihydropyran (III), which is desilylated with TBAF and Ts-OH, yielding the acetylenic dihydropyran (IV). The reaction of (IV) with Ts-OH and isopropanol (V) affords the isopropoxy dihydropyran (VI). The optical resolution of the acetyloxirane (VII) by reaction with O2 and a chiral Co catalyst gives a mixture of (S)-3,4-dihydroxy-2-butanone (VIII) and (R)-acetyloxirane (IX) that is easily separated. The condensation of the chiral oxirane (IX) with the acetylenic dihydropyran (VI) by means of Cp2Zr(H)Cl and Me2Zn, yields the epoxyalcohol (X), which is protected with Tes-Cl and imidazole in DMF to afford the silyl ether (XI). Ring opening of the epoxy group of (XI) with acetylenic dithiolane (XII) by means of BuLi in THF provides the adduct (XIII), which is treated with PPTS to cleave the isopropyl group and oxidized with MnO2 to give the dihydropyranone compound (XIV). The cleavage of the dithiolane ring of (XIV) with bis(trifluoroacetoxy)iodobenzene (PIFA), followed by protection of the OH group with Pmb-trichloroimidate and BF3/Et2O, yields the protected acetylenic ketone (XV), which is submitted to a enantioselective reduction by transfer hydrogenation with isopropanol catalyzed by a chiral Ru catalyst, affording the chiral alcohol (XVI). The protection of the OH group of (XVI) with Tbdms-OTf and lutidine provides the fully protected compound (XVII), which is treated with AgNO3 and N-iodosuccinimide (NIS), giving the iodoethynyl compound (XVIII).