合成路线1

Synthesis of the iodo-L-phenylalanine intermediate (XVII): The condensation of catechol derivative (IX) with methyl orthoformate by means of BuLi and CSA in methanol gives the benzaldehyde dimethyl acetal (X), which is iodinated with I2 and BuLi in ethyl ether to yield the iodobenzaldehyde acetal (XI). The hydrolysis of the acetal group of (XI) by means of HCl in THF affords the 3-hydroxy benzaldehyde derivative (XII), which is treated with benzyl bromide and K2CO3 in refluxing acetonitrile to provide the benzyl protected benzaldehyde derivative (XIII). The Horner-Emmons condensation of aldehyde (XIII) with phosphonate (XIV) by means of TMG in dichloromethane gives the dehydrophenylalanine derivative (XV), which is submitted to an asymmetric hydrogenation with H2 over a chiral Rh catalyst in hot ethyl acetate to yield the L-enantiomer (XVI). Finally, the ester group of (XVI) is hydrolyzed with LiOH in methanol/water to afford the target iodo-L-phenylalanine intermediate (XVII).