Ethyl alpha-oxobenzenebutanoate → N-[1-(R,S)-carboxy-3-phenylpropyl]-L-lysyl-(S)-2-pyrrolidineacetic acid

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Reaction Steps

The product of Step A above is condensed with 2-oxo-4-phenylbutyric acid ethyl ester by the procedure of Example 1, Step E. The diastereomers are separated by silica gel chromatography. The individual diastereomers are converted into the corresponding diacids by saponification as in Example 2 and the -BOC group is removed in hydrogen chloride in ethyl acetate by the procedure of Example 1, Step D. The resulting hydrochloride salt is converted to the free base by absorbing on a strong acid ion exchange resin (Dowex 50W; H+ cycle) and eluting with 3% pyridine in water. Freeze drying affords the desired product, and the S,S,S and R,S,S, diastereomers are separated using reverse phase HPLC.

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