Synthesis of Anabaenopeptins With a Strategic Eye Toward N‐Terminal Sequence Diversity

ABSTRACT A divergent synthesis strategy was developed for producing various anabaenopeptins (AP) for harmful algal bloom monitoring. The synthesis involved on‐resin stepwise pentapeptide assembly on a MeDbz linker then N‐α‐ureido amino acid attachment and cyclization. To manage N ‐methylated amino acids, modified coupling conditions were employed. Lysine's ε‐amino group reacted with the activated MeDbz linker in a self‐cleaving head‐to‐side chain cyclization. Cyclization conditions were optimized by screening different pH levels to control lysine α‐amine cyclization and prevent hydrolysis. Global cleavage and purification afforded the pure anabaenopeptins. This approach proved effective as a general platform for anabaenopeptin synthesis, allowing rapid access to anabaenopeptins A, B, F, and oscillamide Y.