合成路线1

The reaction of 5-(benzyloxy)-3(E)-penten-2-one (I) with trimethylsilyl cyanide (II) by means of a chiral Ti catalyst gives the chiral pentenenitrile (III), which is treated with HCl in ethanol and reduced with DIBAL and NaBH4 in methanol to yield the chiral diol (IV). The selective monosilylation of (IV) by means of TipsCl and imidazole affords the secondary alcohol (V), which is protected with Mom-Cl and DIEA in dichloromethane to provide compound (VI). The debenzylation of (VI) by means of lithium di-t-butyl biphenylide (LiDBB) gives the primary alcohol (VII), which is oxidized with TPAP and NMO in dichloromethane to yield the carbaldehyde (VIII). The reductive allylation of (VIII) by means of allyl trimethoxy silane (IX), AgF and a chiral catalyst affords the secondary alcohol (X), which is esterified with acryloyl chloride (XI) and TEA to provide the acrylate ester (XII). Ester (XII) is submitted to a ring closing metathesis reaction, catalyzed by a Ru catalyst giving the dihydropyranone compound (XIII), which is desilylated by means of HF and TEA in THF to yield the primary alcohol (XIV). The oxidation of (XIV) with DMP in dichloromethane affords the aldehyde (XV), which is condensed with 4-(trimethylsilyl)-3-butyn-2-one (XVI), by means of a chiral La catalyst to provide the acetylenic hydroxyketone (XVII). The reaction of (XVII) with 2,2-dimethoxypropane (XVIII) by means of PPTS gives the acetonide (XIX), which is enantioselectively reduced and catalyzed by a chiral Ru catalyst to yield the secondary alcohol (XX). The reaction of (XX) with Tbdms-OTf affords the silyl ether (XXI), which is treated with NIS and AgNO3 to provide the iodoacetylene derivative (XXII). The diimide reduction of (XXII) using o-nitrobenzenesulfonyl hydrazide (NBSH) gives the cis-iodovinyl compound (XXIII).