合成路线1

The condensation of protected tyrosinaldehyde (I) with 4-O-methyltyrosine methyl ester (II) by means of NaBH(OAc)3 gives the adduct (III), which is cyclized by means of Ph-I(OAc)2 to yield the spiro compound (IV). The 4-nitrophenylsulfonyl protecting group is eliminated with NaS-Ph in DMSO and substituted by Boc by means of Boc2O and pyridine to afford spiro compound (V). The reduction of the carbonyl and double bonds of (V) with H2 over Raney-Ni in ethanol/ethyl acetate provides the spirocyclohexanol derivative (VI), which is further reduced at the ester group by means of LiAlH4 in THF to give the carbinol (VII). The oxidation of (VII) with oxalyl chloride in DMSO/dichloromethane yields the keto aldehyde (VIII), which is cyclized by means of NaOMe in methanol to afford the tricyclic hydroxyketone (IX). The reduction of (IX) with H2 over Raney-Ni in ethanol/ethyl acetate affords the diol (X), which is selectively esterified with dibenzyl hydrogen phosphate (XI), DIAD, TEA and tris(4-chlorophenyl)phosphine in toluene to provide the phosphoric triester (XII). Finally, this compound is debenzylated with H2 over Pd/C in methanol and N-deprotected by means of HCl in dioxane to furnish the target FR-901483.