Scheme 2.

Synthesis of a cyclopentane-based MraY inhibitor with a lipophilic side chain 20 (JH-MR-23).^a

^a Reagents and conditions: (a) IBX, MeCN, 80 °C, 1 h, 70%; (b) methyl isocyanoacetate, Ag₂O, 12, EtOAc, 4 Å MS, −78 to 0 °C, 1.5 days; (c) 4 N HCl, THF, 25 °C, 1 h; (d) CbzCl, NaHCO₃, THF/H₂O (2/1), 0 °C, 15 h, 20% for three steps; (e) 8, NIS, TESOTf, CHCl, 4 Å MS, 25 °C, 30 min, 60%; (f) Zn powder, NH₄Cl, EtOH/H₂O (3/1), 25 °C, 1.5 h; (g) Boc₂O, NaHCO₃, CH₂Cl₂, 25 °C, 2 h, 52% for two steps; (h) Pd/C, H₂, MeOH, 25 °C, 3 h; (i) 16, NaBH₃CN, HOAc, MeOH, 25 °C, 15 h, 59% for two steps; (j) Zn powder, NH₄Cl, MeOH, 25 °C, 25 h; (k) 18, EDCl, HOBt, CH₂Cl₂, 25 °C, 20 h, 12% for two steps; (l) Ba(OH)₂·8H2O, THF/H₂O (4/1), 0 to 25 °C, 20 h, 40%; (m) 80% TFA in H₂O, 25 °C, 18 h, quantitative.