合成路线1

The oxidation of the chiral 2(R)-(benzyloxymethyl-4-phenyl-1-butanol (I) with (COCl)2 and TEA in DMSO/dichloromethane gives the corresponding aldehyde (II) , which by a pinacol coupling promoted by VCl3, Zn and 1,3-dimethylimidazolidin-2-one (DMI) in dichloromethane yields the glycol (III) as a mixture of all the possible enantiomers. The protection of the glycol function of (III) by means of 2,2-dimethoxypropane (IV), 2-methoxypropene and CSA in acetone affords the isopropylidene ketal (V), which is debenzylated by hydrogenation with H2 over Pd/C in aq. NaHCO3/EtOAc to provide the hexane-1,6-diol (VI). The oxidation of diol (VI) with RuCl3 and NaIO4 in acetonitrile/water/dichloromethane gives the adipic acid derivative (VII), which is treated with disuccinimidyl carbonate (VIII) to yield the corresponding enantiomeric mixture of activated esters, which is resolved by column chromatography to isolate the (R,R)-activated ester (IX). The reaction of (IX) with (1S,2R)-1-amino-2-indanol (X) in hot dichloroethane (DCE) affords the diamide (XI), which is finally deprotected (elimination of the isopropylidene group) by means of FeCl3.6H2O in dichloromethane to provide the target (R,R,R,R)-dihydroxydiamide.