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

Abstract

l-prolyl- l-m-[bis(chloroethyl)amino]-phenylalanyl- l-norvaline ethyl ester hydrochloride, 4 (and its 3H and 14C doublylabeled 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.