合成路线1

The introduction of a methylene group in (XXXV) by reaction with the Grignard reagent TMSCH2MgCl and Pd(PPh3)3 as catalyst in ethyl ether, affords the trimethylsilylmethyl compound (XXXVI), which is chlorinated with N-chlorosuccinimide (NCS) in methanol and treated with 2-methoxypropene (XXXIII) and PPTS to provide the chloro derivative (XXXVII). Regioselective hydroxylation of (XXXVII) is performed by enolization with LDA, followed by oxidation with MoO5/pyridine in HMPA and final acylation with Ac2O to give the alpha-acetoxy compound (XXXVIII). This acetate (XXXVIII) is isomerized to the corresponding beta-isomer (XXXIX) by heating with a base such as DBN. The dihydroxylation of the exo-methylene moiety of (XXXIX) with OsO4 and pyridine in ethyl ether yields the corresponding dihydroxy compound (XL), which is cyclized with DBU in refluxing toluene in order to form the oxetane ring of (XLI). The removal of the MOP group of (XLI) with PPTS, followed by reprotection with TES-Cl in DMF gives the triethylsilyl ether (XLII). Cleavage of the cyclic benzylidene ketal of (XLII) with H2 over Pd(OH)2, followed by reaction with triphosgene and pyridine yields the cyclic carbonate (XLIII), which is acetylated at the tertiary OH group of with acetic anhydride and DMAP to yield the acetoxy compound (XLIV). Reaction of (XLIV) with phenyl lithium in THF gives the benzoate (XLV), which is selectively desilylated with HF/pyridine and reprotected with 2,2,2-trichloroethyl chloroformate (Troc-Cl) yielding the intermediate (XLVI). Compound (XLVI) is again desilylated with tris(diethylamino)sulfoxonium difluorotrimethylsiliconate (TASF) affording the secondary alcohol (XLVII).