Total Synthesis of LL-A03411-Beta1

The first total synthesis of the cyclic depsipeptide antibiotic LL-A03411-beta1 (LL) is described. The configuration of the -methyltryptophan (-MeTrp) residue was established by preparing all four stereoisomers of Fmoc--MeTrp which were used for the synthesis of LL via Fmoc solid phase peptide synthesis. The most active of the four peptides was the one containing (2R,3R)--MeTrp. The activity of LL was strongly inhibited by cardiolipin (CL), but not other common phos-pholipids found in bacterial cell membranes suggesting that LL interacts with CL in the lipid membrane