合成路线1

An alternative route to the precursor N-acyl tripeptide (VIII) consists of coupling of N-Cbz-L-tert-leucine (XIII) with the bicyclic amino ester (XIV) to afford the protected dipeptide (XV), from which the N-Cbz group is removed by catalytic hydrogenolysis over Pearlman’s catalyst, yielding (XVI). The dipeptide ester (XVI) is then coupled with N-Cbz-L-cyclohexylglycine (XVII) to give (XVIII), which is further deprotected by catalytic hydrogenolysis to afford the tripeptide ester (XIX). After acylation of (XIX) with pyrazinecarboxylic acid (III) employing CDI, the resulting N-acyl tripeptide tert-butyl ester (XX) is treated with HCl in formic acid to provide the target intermediate (VIII) (3). Scheme 2.