Scheme 4. Synthesis of monovalent control compounds (2, 3). Reagents and conditions: (a) methylamine, diglycolic anhydride, THF, rt, 60-70% (b) 12, EDCI, HOBt, TEA, DMF, 0 °C, 40–50% (c) H2, Pd/C, MeOH, rt, 50–60% (d) diglycolic anhydride, THF, rt, 40–50% (e) 4 or 6β-naltrexamine, EDCI, HOBt, TEA, DMF, 0 °C, 20–40%.
