A general strategy for the synthesis of destruxin analogues is described and applied to a particular example, D-Lac-6 destruxin E. The tetrapeptide Boc-Ile-N-MeVal-N-MeAla-beta-Ala-OMe (2) was chosen as the basic starting compound, and its preparation was optimized. This fragment was then coupled with the compound (D)Lac-Pro, and the resulting peptide was cyclized by the DEPC or DPPA/HOBt/DMAP methods at 21 and 30% yield, respectively. The biological activity of the analogue obtained was established by injection to an insect host.