合成路线1

Partial hydrolysis of chiral cyclopropanedicarboxylate (I) with 1 equivalent of NaOH in aqueous isopropanol provided monoester (II), which was converted to acid chloride (III) by treatment with SOCl2. Palladium-mediated coupling of (III) with the organozincate from 9-xanthenylmethyl iodide (IV) and Zn-Cu couple afforded (S,S)-ketone (V). Basic hydrolysis of (V) then provided ketoacid (VI), which was transformed into a mixture of diastereomeric hydantoins (VII) under Bucherer-Berg conditions using an excess of KCN and (NH4)2CO3 in water at 55 C. Subsequent reaction of (VII) with 4-methoxybenzyl bromide (VIII) and KHCO3 in DMF produced both N- and O-alkylation to provide a diastereomeric mixture, which was separated by column chromatography. Hydrolysis of isomer (IX) with aqueous Ba(OH)2 in a pressure reactor at 200 C gave the target (S,S,S)-amino acid, which was purified by cation-exchange chromatography.