Scheme 4. Illustrative example of the synthesis of some final macrocyclic peptidomimetics using a route incorporating two couple steps (i.e. B/C/C/P). The lowest energy conformations (molecular shapes) of some final library compounds (27, 28, 32–34) are shown46 (conformational search by MOE software package47). Conditions:(a) (i) EDC·HCl, HOBt, Boc-l-Glu-OMe (12b), NEt3, CH2Cl2, rt; (ii) TMSCl, MeOH, 0 °C to rt; (b) (i) EDC·HCl, HOBt, 11i or 11m or 11j, NEt3, CH2Cl2, rt; (c) (i) [Cp*RuCl]4, toluene, reflux; (ii) HCl–dioxane (4.0 M); (d) AcOH–NMM* (1.25 : 1, molar ratio), 2-Butanol, Microwave irradiation (T = 150 °C). NMM*: morpholinomethyl-polystyrene (loading = 3.51 mmol g–1).
