合成路线1

Bis-tetrahydropyran intermediate (XXIV). The asymmetric addition of Ipc2B-crotyl to 5-benzyloxypentanal (XI) gives the secondary alcohol (XII), which is protected with Boc2O and NaHMDS in THF yielding the carbamate (XIII). The reaction of (XIII) with IBr in toluene affords the iodinated cyclic carbonate (XIV), which is converted into the epoxide (XV) by reaction with K2CO3 in methanol/water. The reaction of the epoxide (XV) with 1,3-dithiane (XVI) by means of BuLi in THF/HMPA provides the dihydroxy compound (XVII), which is converted into the acetonide (XIX) by reaction with 2,2-dimethoxypropane (XVIII) and PPTS . The condensation of (XIX) with the tetrahydropyran-2-carbaldehyde intermediate (X) by means of BuLi in ethyl ether/HMPA gives the bis acetonide derivative (XX) (1), which is deprotected by means of CSA, cyclized by means of Hg(ClO4)2 and acylated with Piv-Cl and pyridine to yield the bis tetrahydropyranyl intermediate (XXI). The silylation of the OH group of (XXI) by means of Tbdms-OTf, followed by debenzylation by means of HCOONH4 and Pd/C affords the butanol derivative (XXII), which is successively silylated, first with Tbdps-Cl /imidazole and then with Tes-OTf and lutidine to provide the fully silylated compound (XXIII). Finally, the elimination of the pivaloyl group of (XXIII) by means of DIBAL in THF, followed by reaction with I2, PPh3 and imidazole in toluene gives the iodomethyl bis tetrahydropyran intermediate (XXIV) (2).