a) N-Protected L-Leucine activated as the pentafluorophenyl ester (I) is coupled with L-prolinamide (II), and the resulting dipeptide (III) is deprotected te (IV) and coupled with L-pyro-2-aminoadipic acid pentatluorophenyl ester (V) to give RGH-2202.
b) Large scale preparation of L-pyro-2-aminoadipic acid (IX) is accomplished by oxidation of the N-protected L-lysine derivative (VI) with KMnO4 followed by deprotection to (VIII) and cyclization.