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. Author manuscript; available in PMC: 2017 Jan 12.
Published in final edited form as: Bioorg Med Chem. 2014 Apr 24;22(12):3083–3090. doi: 10.1016/j.bmc.2014.04.030

Scheme 1.

Scheme 1

(a) Boc-glycine, EDC, HOBt, DIPEA, THF, rt, 16 h, 94%; (b) TFA, DCM, rt, 1 h; (c) Boc-β-alanine, EDC, HOBt, DIPEA, THF, rt, 16 h, 60% over 2 steps; (d) D-pantolactone, EtOH, TEA, 80°C, 16 h, 40% over 2 steps; (e) chloroacetyl chloride, THF, rt, 16 h, 89%; (f) tert-butyl 3-aminopropylcarbamate, K2CO3, DMF, 50°C, 16 h, 60%; (g) ethylenediamine, DMF, rt, 30 min, 82%; (h) EDC, DIPEA, HOBt, THF, rt, 16 h, 79%; (i) TFA, DCM, rt, 3 h; (j) 80% AcOH, rt, 16 h, 66% over 2 steps; (k) p-chloroaniline, THF, rt, 12 h, 88%; (l) Boc-propane-1,3-diamine, THF, 65°C, 24 h, 86%; (m) TFA, DCM, rt, 1 h; (n) D-pantolactone, EtOH, TEA, 75°C, 24 h, 59% over 2 steps; (o) 1-bromopentane, NaN3, CuSO4·5H2O, sodium ascorbate, DMF, H2O, 100°C, 16 h, 81%; (p) 1-pentyne, NaN3, CuSO4·5H2O, sodium ascorbate, DMF, H2O, 100°C, 16 h, 26%; (q) TFA, DCM, rt, 1 h; (r) D-pantolactone, EtOH, NEt3, 75°C, 16 h, 14–46% over 2 steps; (s) pentanal, 1% AcOH/MeOH, rt, 5 h; (t) NaBH4, MeOH, 0°C-rt, 1 h; (u) TFA, DCM, rt, 1 h; (v) D-pantolactone, EtOH, NEt3, 75°C, 24 h, 52% over 4 steps; (w) butyric acid, EDC, HOBt, DIPEA, THF, rt, 16 h, 53%; (x) TFA, DCM, rt, 1 h; (y) Boc-β-alanine, EDC, DMAP, DIPEA, THF, rt, 16 h, 64% over 2 steps; (z) D-pantolactone, EtOH, NEt3, 75°C, 16 h, 11% over 2 steps.