Fig. 4
Gram-scale total synthesis of teixobactin. a (1) 4 equiv. I2, 5 equiv. NaHCO3, 0 °C, 1 h; (2) MeOH/AcOH (9:1), 30 °C, 15 min, 66% for 2 steps; b (1) 3 equiv. LiOH, THF/H2O; (2) Pd(OH)2/C, H2, MeOH/AcOH (9:1). c 3 equiv. CbzOSu, 4 equiv. DIEA, DCM, 30 °C, 4 h, 80%; d (1) 30 % TFA, 30 °C, 30 min; (2) 1.2 equiv. Boc-Ser(tBu)-OH, 1.2 equiv. HATU, 3 equiv. DIEA, DCM/DMF, 30 °C, 3 h; e (1) 1.5 equiv. Fmoc-Ile-OH, 1.5 equiv. EDCI, 0.2 equiv. DMAP, DCM, 12 h; (2) 33% Et2NH, 30 °C, 15 min; 79%; f (1) 33% Et2NH, r.t., 10 min; (2) 3 equiv. Alloc-Ala-OH, 3 equiv. HATU, 3 equiv. DIEA, DCM/DMF, 30 °C, 3 h, 71%; g 2 equiv. LiOH, THF/H2O (3:1), 0 °C, 4 min; h 2.5 equiv. compound 12, 2 equiv. DEPBT, 2.5 equiv. DIEA, THF/DMF, 30 °C, overnight, 63%; i (1) 0.3 equiv. Pd(PPh3)4, 2 equiv. 1,3-dimethylbarbituric acid, DCM, 30 °C, 1 h; (2) 4 equiv. HATU, 4 equiv. HOAT, 8 equiv. DIEA, DCM/DMF, 30 °C, 24 h, 58%; j (1) 3 M HCl, 15 min; (2) 1 equiv. compound 17, 1.2 equiv. DEPBT, 1.2 equiv. DIEA, DMF,12 h; k (1) Pd(OH)2/C, H2, MeOH/HCOOH, 1 h; (2) TFA:TIPS:H2O: 95:2.5:2.5. 31% from compound 16
