Development of NCL in Thiolactone Peptide Synthesis

As mentioned in the introduction to this chapter, the recent discovery of thiolactone peptides as potential antimicrobial agents, based on flieir ability to act as antagonists of natural auto-inducing peptides (AIP), prompted the new synthetic achievements, which permitted the synthesis of these cyclic peptide inhibitors. Here, we discuss the most recent achievement in the synthesis of AIP mimics, based on an original linker for the Fmoc-based solid-phase methodology. 

In all of the peptide bond-forming steps, N-Boc-AA is activated by the HBTU/ DIEA system, and the Boc group removed with anhydrous HF. The latter creates a bottleneck in the process, and the replacement of Boc by an Fmoc protecting group became the key objective. 

Design of the new linker, its synthesis and successful appUcation to novel AIP synthesis was recently achieved by the same group [36]. To overcome the limitations 

cold 1 1 mixture TFA/waler added dropwise loSinTHF, slirrirtgatO C for4. h iv. DCM, mol. ratio Oe Martin periodinarte 6 (1.2 1) stirring urtder at r.L for2h V. NaOCI, 2 melhyl 2 bulene. Na-phosphale buffer. 

WakHjp remaining amino groups acylated by Ac O/DlEA/DMF (1 1 8) two treatments for 10 min, deprotection ofTBSbyTBAF(1M in THF), r.t., overnight 

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