合成路线1

The condensation of the chiral aldehyde (I) with the phenyllithium compound (II) in the presence of magnesium ion gives, after protection of the resulting vicinal diol as a boronate, the cyclization precursor (III). The cyclization of (III) by means of TiCl2 in dichloromethane yields the tricarbocyclic compound (IV), which is silylated at the vicinal diol with butyllithium and di-tert-butylsilyl chloride in THF, reduced with DIBAL in dichloromethane and silylated with TBS-OTf to afford intermediate (V). Singlet oxygen oxygenation of the diene moiety of (V), followed by a treatment with tributyl tin hydride produced the peroxide bonds cleavage and removal of the phenylsulfanyl group; and elimination of the benzyl protecting group by hydrogenation, followed by reprotection of the vicinal diol with benzaldehyde dimethylacetal gave a mixture of two diastereoisomers (VI). This mixture was treated with diethylzinc/chloroiodomethane, only the beta-isomer underwent the cyclopropanation, followed by Dess-Martin periodinane (DMP), affording the ketone (VII). Elimination of the benzylidene group of (VII), followed by reaction with triphosgene, and desilylation with TBAF provided the cyclic carbonate (VIII). The reprotection of the free hydroxy groups of (VIII) with benzaldehyde dimethylacetal, followed by hydrolysis of the cyclic carbonate group affords intermediate (IX). This compound was treated with samarium iodide and TBAF to induce the cleavage of the cyclopropane ring resulting in a mixture of enol (X) and ketone (XI). The enol was treated with NaOMe to complete the ketonization to (XI). The vicinal diol of (XI) was initially protected as a boronate with phenylboronic acid and the remaining hydroxy group was silylated with TBS-OTf. After removal the boron-protecting group, selective Dess Martin oxidation and protection of the remaining hydroxy group with 2-methoxypropene, the dione (XII) was obtained. The reaction of (XII) with KHMDS and PhNTf2 yielded the corresponding enol, which was reacted with trimethylsilyl magnesium chloride in ether to give the allylsilane (XIII). The reaction of (XIII) with N-chlorosuccinimide (NCS) and 2-methoxypropene yielded the chlorinated compound (XIV), which was treated successively with LDA to generate the enol, oxidized with MoO5, and acetylated with acetic anhydride to provide the acetoxy derivative (XV). The oxidation of the exocyclic double bond of (XV) with OsO4 and pyridine gave the corresponding diol, which by treatment with DBU in refluxing toluene and silylation with TES-Cl yielded the oxetane derivative (XVI).