Cycloaddition routes to pyrazole and pyrazoline amino acids

In recent years, the design and synthesis of structures that can potentially mimic the properties of the peptide bond have been of great interest to biological chemists. We are investigating the synthesis of novel pyrazoline-based structures as potential peptide mimetics. The pyrazoline unit is assembled by 1,3-dipolar cycloaddition of nitrile imines, which are generated in situ from hydrazonyl chlorides. We have investigated two routes to afford the hydrazonyl chloride, (1) via a hydrazone and (2) via a hydrazide, both of which have resulted in the successful synthesis of the desired pyrazolines. Subsequent syntheses have been carried out using a variety of different dipoles and dipolarophiles. We have taken approach (1) and used this to synthesize a pyrazole as one major enantiomer. [Illustration omitted.] This pyrazole has been subject to peptide couplings to form a complete peptide mimetic. [Illustration omitted.] NMR studies have been carried out on the synthesized peptide mimetic to determine the degree of hydrogen bonding and β-turn characteristics.