Solid-phase total synthesis and antimicrobial activities of loloatins A-D.

The first total synthesis of the decapeptide antibiotics loloatins A–D (1–4), originally isolated from the marine bacterial isolate MK-PNG-276A, possibly in the genus Bacillus, was accomplished by solid-phase peptide synthesis (SPPS), followed by ‘head-to-tail’ cyclization of the activated linear precursors, without protection of nucleophilic side-chain functions, on a safety-catch resin. The synthetic peptides were equally active as the natural products isolated from the bacterial source and found to possess similar bacterial selectivity as other members in the family of amphipathic antimicrobial cyclic decapeptides.