合成路线1

The treatment of (XI) under the Sharpless asymmetric epoxidation conditions (but using (+)-DET and titanium tetraisopropoxide) gives, after cyclization with NaOH, 1(S)-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2(R)-yl)-1,2-ethanediol (XVI), which is benzoylated with 4-nitrobenzoic acid (XVII), DEAD and PPh3 yielding the dibenzoate (XVIII), with inversion of the configuration at the OH group. The hydrolysis of (XVIII) with NaOMe in methanol affords, 1(R)-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2(R)-yl)-1,2-ethanediol (XIX), which is selectively tosylated with TsCl and pyridine giving the monotosylate (XX). The cyclization of (XX) with NaOMe furnishes the expected epoxide (XXI), which is finally condensed with the previously described intermediate amine (XV).