Cyclic lactams peptidomimetics

In the following discussion a selection of optimized procedures is presented for the synthesis on solid support of homodetic monocyclic and bicyclic as well as mixed homodetic/ heterodetic bicyclic peptides that contain at least one lactam ring, whereas heterodetic cyclic peptides containing other than amide bonds or peptidomimetics are not discussed here because of their unlimited diversity. 

The field of peptide synthesis is never far removed from the study of natural products, many of which exhibit peptide and peptidomimetic structures. It is fitting that this treatise be concluded with a section on the synthesis of key peptide-based natural products. Section 16 commences with the synthesis of bacitracin)30 a cyclic peptide with antibiotic properties. The synthesis of this target structure is carried out in solution and by solid-phase chemistry. The molecule contains a lactam-bridged cyclic heptapeptide with a pendent tripeptide (Section 16.1.1). An elegant route to the synthesis of the thiazoline building block is included. 

Diazabicyclo[4.3.0]nonene-based peptidomimetics with a quaternary chiral centre are prepared via intramolecular condensation of A -aminopropyl-y-lactam [27]. Reductive amination of oxazolidinone aldehydes with A -monoprotected propylenediamine give A -phthalimidopropyl lactams however, trials of cyclization to bicyclic amidines after deprotection under dehydration conditions are unsuccessful. To solve this problem, the phthalimides are converted to thiolactams with Lawesson reagent. Deprotection followed by treatment with mercury (11) chloride (HgCl2) yields desired cyclic amidines (Scheme 3.14). 

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