Synthesis of Dipeptides with [CH20] Amide Bond Mimetics

This chapter describes the synthetic procedures leading to ether dipeptide isosteres of the Phe-ψ[CH 2 O]-spiro-C x ( 9a–9e , Fig. 1 ) and Phe-ψ[CH 2 O]-Allylglycine ( 13 , Fig. 2 ). Development of methods which lead to mimetics of amide bonds is central to the conversion of peptide leads into pharmaceutically viable molecules. Our strategy utilizes template 1 , which provides derivatives 6b–6e upon alkylation with I, Cl-alkanes (C 3 –C 6 ). Subsequent Finklestein conversion to iodides 7b–7e is then followed by cyclization to spirocyclic derivatives 5b–5e (Fig. 3 ).   Figure 1.  Synthesis of Phe ψ[CH 2 O]Spiro isosteres 9a–9e .   Figure 2.  Synthesis of Phe ψ[CH 2 O]Allylglycine 13   Figure 3.  Synthesis of morpholinones 5b–5e .