合成路线1

The synthesis of the C22-C34 subunit (C12-C16 of the chemical name) of FK-506 has been reported: The condensation of the chiral aldehyde (I) with the (S)-allenyl stannane (II) by means of boron trifluoride ethearate in dichloromethane yields an epimeric mixture of the acetylenic alcohol (III), which by protection with p-methoxybenzyl (PMB) trichloroacetimidate, followed by chromatographic separation, gives the enantiomerically pure protected acetylenic diol (IV). The reduction of (IV) with bis(2-methoxyethoxy)aluminum hydride in THF affords the (E,E)-dienic alcohol (V), which is submitted to a Sharpless asymmetric epoxidation with (-)-diethyl tartrate [(-)-DETR], titanium tetraisopropoxide and tert-butyl hydroperoxide (TBHP) in dichloromethane, yielding the chiral epoxy alcohol (VI). The reduction of (VI) with bis(2-methoxyethoxy)aluminum hydride in THF affords the partially protected triol (VII), which is finally dehydrogenated with dichlorodicyanobenzoquinone (DDQ) in dichloromethane to give the chiral 1,3-dioxane (VIII), which is the desired intermediate.