De Novo Design To Synthesize Lanthipeptides Involving Cascade Cysteine Reactions: SapB Synthesis as an Example

Lanthipeptides are a family of ribosomally synthesized peptides that have crucial biological functions. However, due to their complicated structures, the total synthesis of lanthipeptides is challenging. Here, a novel strategy to construct lanthipeptides is described, which involves cascade reactions of cysteine, including Cys disalkylation elimination, Michael reaction, and native chemical ligation. We utilized this strategy to synthesize lanthipeptide SapB as an example. This methodology has the potential to obtain lanthipeptides and their analogues for biological research and drug discovery.