合成路线1

The alkylation of diethyl acetamidomalonate (II) with 1-bromo-3-phenylpropane (I) by means of NaOEt provided the substituted malonate (III), which upon hydrolysis and further decarboxylation gave rise to racemic 2-(acetylamino)-5-phenylpentanoic acid (IVa-b). Kinetic resolution employing Acylase I in the presence of CoCl2 produced a mixture of the (S)-amino acid (V) and the unaltered (R)-amide (VI), which were separated by differential solubility. The desired (R)-amide (VI) was hydrolyzed with aqueous HCl and then treated with EtOH to produce aminoester (VII). Subsequent coupling of (VII) with N-Boc-alpha-aminoisobutyric acid (VIII) employing 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and N-methylmorpholine (NMM) yielded the protected dipeptide (IX). Basic hydrolysis of the ethyl ester of (IX) afforded the intermediate (X).