Studies on RA Derivatives. V. Synthesis and Antitumor Activity of Ala²-Modified RA-VII Derivatives

Abstract

A number of RA-VII derivatives having various amino acids including proline (6), pipecolic acid (11), norvaline (12), ornithine (14), aspartic acid (15) and methionine (20) in place of Ala² have been synthesized from RA-X methyl ester (3) and evaluated for cytotoxicity to P388 leukemia and KB cells in vitro. Comparison of the cytotoxicity of these compounds suggests that the polarity and the length of the 2nd amino acid residue affect the activity. An NMR study revealed that, in solution, 6 and 11 are locked in one conformational state, corresponding to conformer A of RA-VII.