Acidic coupling and aminolytic TFA cleavage approaches in a new synthesis of an L-m-sarcolysin containing antitumor tripeptide ester

L-propyl-L-m-[bis(chloroethyl)amino]-phenylalanyl-L-norvaline ethyl ester hydrochloride, 4 (and its ³H and ¹⁴C doubly-labeled version) was synthesized starting with reacting unprotected L-m-sarcolysin, 1, with TFA-Pro-Cl in an acidic system to yield TFA-Pro-L-m-sarcolysin, 2, which was transformed to the TFA-tripeptide ethyl ester, 3. Selective aminolytic cleavage of the TFA group with butylamine in abs. ethanol, followed by neutralization with HCl gave 4.