Lanthionine macrocyclization by in situ activation of serine

Abstract
The present report details a straightforward, solid‐phase approach to cyclolanthionine peptides. After stepwise assembly of the linear sequence and transformation of a single exposed serine to bromoalanine using P(Ph)3/CBr4, the detritilation of a cysteine side‐chain sets the stage for a base‐promoted macrocyclization. The entire procedure can be carried out in a solid‐phase vessel using conventional 9‐fluorenylmethyloxycarbonyl/tert‐butyl‐based chemistry and is amenable to automated format. The utility of this novel procedure is demonstrated by the synthesis of two previously reported lanthionine‐containing cyclic peptides.