|Abstract:||Didemnin A, a cyclic depsipeptide isolated from a Caribbean tunicate, was synthesized by coupling two key fragments, (Boc-(3S,4R,5S)-Ist(TBDMS)-(2R,S;4S)-Hip-Leu-Pro-OH (Fragment I)) and (Z- scD-MeLeu-Thr(H-Me$\sb2$Tyr)-OTMSe) (Fragment II). Fragment I was synthesized, in turn, from Boc-(3S,4R,5S)-Ist(TBDMS)-OH, Bn-(2R,S;4S)-Hip-OH, Boc- scL-Leu-OH and H- scL-Pro-OMe by stepwise elongation of the peptide chain, starting from H-Pro-OMe. Fragment II was synthesized from Z- scD-MeLeu-OH, H- scL-Thr-OMe and Boc- scL-Me$\sb2$Tyr-OH, starting from Z- scD-MeLeu-OH. The heptapeptide Z- scD-MeLeu-Thr(Boc-(3S,4R,5S)-Ist-(2R,S;4S)-Hip-Leu-Pro-Me$\sb2$Tyr) -OTMSe was synthesized by coupling the two fragments between proline and dimethyltyrosine using Bop-Cl. After deprotection of TMSe and Boc groups, the cyclization was accomplished between threonine and isostatine, again using Bop-Cl. The $\sp1$H NMR and mass spectra and rotation of the synthesized N-Z-didemnin A are the same as those of natural N-Z-didemnin A.