Heterocyclic amino acids are useful for mimicry of peptide turn conformations to study relationships between structure and biological activity. Our presentation describes a stereo-controlled ring-closure metathesis (RCM)-transannular lactam cyclization strategy that gives functionalized azabicyclo[X.Y.0]alkanone amino acids possessing different heterocycle ring sizes (e.g., 5,5-, 5,6-, 6,4-, 6,5-, 6,6-, and 7,5) from their 8–10-member dipeptide lactam precursors. Lactams were made by coupling respectively omega-olefin alpha-amino acid building blocks followed by RCM.&lt;span style="font-size:10.8333px"&gt; &lt;/span&gt;The influence of a hypervalent reagent, solvent and ring size were revealed in mechanistic study of the transannular cyclization. Moreover, lactam iodoacetoxylation gave a second form of peptidomimetic. X-ray crystallographic and spectroscopic analyses of the heterocycles demonstrated their potential to mimic the central residues of ideal type I, II', II and VI beta-turns.

Transannular cyclization and Iodoacetoxylation approaches to heterocycle peptidomimetics

255th National Meeting (2018)

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