合成路线1

A practical total synthesis of KRN-7000 has been reported: The reaction of D-lyxofuranose (I) with acetone and sulfuric acid gives the acetonide (II), which is tritiated with trityl chloride and pyridine in dichloromethane to the protected lyxose (III). The condensation of (III) with triphenyltridecylphosphonium bromide (IV) by means of butyllithium in THF yields the alcohol (V) with the suitable (2R,3S,4R)-configuration. The mesylation of (V) with mesyl chloride and pyridine affords the mesylate (VI), which is treated with aqueous HCl in dichloromethane to obtain the unsaturated triol (VII). The hydrogenation of (VII) with H2 over Pd-BaSO4 in THF affords (2R,3R,4R)-2-(methanesulfonyloxy)octadecane-1,3,4-triol (VIII), which by reaction with sodium azide in hot DMF yields the corresponding azide (IX). The protection of the primary alcohol of (IX) with trityl chloride and pyridine affords the azide diol (X), which is treated with benzyl bromide and NaH in DMF to give the fully protected triol (XI). The reduction of the azido group of (XI) with H2 over Pd/C in propanol/methanol affords the amine (XII), which is acylated with hexacosanoic acid (XIII) and WSC-HCl yielding the corresponding amide (XIV). Elimination of the trityl group of (XIV) with HCl in methanol/dichloromethane gives the primary alcohol (XV), which is condensed with tetra-O-benzyl-beta-D-galactopyranosyl bromide (XVI) by means of tetrahexylammonium bromide in toluene/DMF yielding the fully benzylated KRN-7000 (XVII). Finally, this compound is debenzylated by a treatment with Pd(OH)2 on charcoal and 4-methylcyclohexene in ethanol.