合成路线1

Protection of the amino group of diethanolamine (I) with diethyl chlorophosphate in the presence of triethylamine gave N-(diethoxyphosphoryl)ethanolamine (II). Further treatment of (II) with methanesulfonyl chloride yielded the corresponding bis(mesylate) (III). Reaction of 2,6-bis(bromomethyl) pyridine (IV) with NaCN in the presence of cetyl trimethylammonium bromide under phase-transfer conditions produced dinitrile (V), which was hydrogenated over Raney Nickel to afford diamine (VI). Subsequent condensation of (VI) with p-toluenesulfonyl chloride gave bis(sulfonamide) (VII). Cyclization of bis(mesylate) (III) with bis(sulfonamide) (VII) in the presence of Cs2CO3 gave rise to macrocycle (VIII). Selective deprotection of the diethoxyphosphoryl group by means of HBr in AcOH gave (IX). This was dimerized with alpha,alpha'-dibromo-p-xylene (X) in the presence of K2CO3 in refluxing acetonitrile to give the tosyl-protected dimer (XI). Deprotection of the tosyl groups of (XI) was achieved by reductive treatment with sodium amalgam. The title compound was then isolated after conversion to the octahydrobromide tetrahydrate salt.