Unnatural tertiary amines

Our studies commenced with exploring various catalysts and promoters of the aldol reactions (Table 2). To simplify the analysis, only diastereomerically pure Michael adduct 14a was used in the screening of reaction conditions. Initially, the intramolecular double-cyclization proved to be difficult as pro-line catalysis (entry 1), soft enolization (entry 2), and tertiary amines (entries 3 and 4) were unsuccessful. Acidic conditions (pTSA) provided a positive result as the steroid diol 24 with the unnatural C13/C14 configuration was formed. Unfortunately, the formation of significant side products along with 24 complicated isolation of this product. 

It is well established that control of peptide conformation allows the tertiary structure vital for enzyme activity. Unnatural a and p amino acids are particularly useful in this regard for designing peptides with controlled conformation and thus targeted function, but amino add mimics have also been put to good effect in this regard. This was the goal of Pannecoucke when he successfully synthesized en antiopure monofluorinated allylic amines as site spedfic amino acid mimics in peptides (Scheme 7.12) [38]. 

---