Synthesis and biological activities of [N-MeLeu5]- and [N-MePhe5]-didemnin B

Abstract Based on information from X-ray, NMR, and SAR data, the N , O -diMeTyr 5 unit of didemnin B was believed to be important for biological activity. To determine the importance of aromaticity and the role of the methoxy group in this unit, two analogs were synthesized in which the N , O -diMeTyr 5 moiety was replaced with N -MeLeu and N -MePhe. Preliminary testing showed that the analogs retained antitumor activity and the ability to inhibit protein biosynthesis in vitro .