Progress in Development of Coronavirus Inhibitors
- Corresponding author: He Wanlin, hwl1558714@163.com Cai Yan, caiyan_86@163.com
Citation:
Zhao Peipei, Zheng Wenhui, Bu Min, He Wanlin, Cai Yan. Progress in Development of Coronavirus Inhibitors[J]. Chemistry,
;2020, 83(8): 674-689.
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Reagents and conditions: (a) Me3SiCl, MeOH, 0℃, then Boc2O, Et3N, 0~25℃; (b) LiN(SiMe3)2, THF, -78℃, then BrCH2CN; (c) H2, PtO2, MeOH, CHCl3, 25℃, then NaOAc, reflux; (d) NaBH4, LiCl, THF, EtOH, 25℃; (e) Pyridine-SO3, DMSO, CH2Cl2, Et3N, 10℃; (f) [EtO2CCHPO(OEt)2]-Na+, THF, -78℃; (g) HCl, 1, 4-dioxane, rt; (h) HBr, NaNO2, KBr, H2O, 10℃; (i) KOH, EtOH, 0℃; (j) Me2SO4, CH2Cl2, (PhCH2)Et3NCl, rt, 24 h; (k) CuBr-Me2S, THF, 35℃, 1h; (l) (CF3SO2)2O, 2, 6-lutidine, CH2Cl2, 0℃, 40 min; (m) 1, 10-carbonyldiimidazole, THF, rt, 1 h; (n) CH3CO2tBu, LiN(i-Pr)2, THF, -78℃; (o) NaH, THF, 0 ℃, 30 min, then triflate 6, THF, 0℃ to rt, 24 h; (p) CF3CO2H, CH2Cl2, rt; (q) H2, Pd/C, Boc2O, MeOH, rt; (r) LiOH, H2O, 1 h, 0℃; (s) allyl iodide, Cs2CO3, DMF, 45℃; (t) N-methylmorpholine, CH2Cl2, 0~25℃; (u) Pd(PPh3)4, morpholine, THF, 25℃; (v) HOBt, EDCI, NMM, DMF, 0~25℃.
Reagents and conditions: (a) (Boc)2O, NaOH, 1, 4-dioxane/H2O; (b) PhCH2Br, K2CO3, DMF; (c) TFA, CH2Cl2; (d) EDCI, HOBT, Et3N, CH2Cl2; (e) TFA, CH2Cl2; (f) EDCI, HOBT, Et3N, CH2Cl2; (g) TFA, CH2Cl2; (h) HATU, DIEA, CH2Cl2; (i) H2, Pd/C; (j) HATU, DIEA, CH2Cl2.
Reagents and conditions: (a) LiHMDS, BrCH2CN, -78℃; (b) H2, 50 psi, PtO2, MeOH, THF; (c) Na2CO3, MeOH, CHCl3; (d) LiOH, THF/H2O, 0℃, quant; (e) EtOCOCl, Et3N, THF, -30℃, then CH2N2/Et2O 30℃ to rt; (f) 48% HBr, THF, 0℃; (g) phthalhydrazide, NaH, DMF, rt; (h) TFA, CH2Cl2, 0℃; (i) Ac-Val-Thr(OBn)-Leu-OH, HBTU, DIPEA, DMF, rt; (j) H2(1atm), Pd/C, MeOH, rt; (k) TFA, TMSOTf, 0℃.
Reagents and conditions: (a) TEA, CH2Cl2; (b) 1mol/L NaOH, MeOH; (c) HATU, DMF; (d) NaBH4, MeOH; (e) DMP, NaHCO3, CH2Cl2; (f) AcOH, CH2Cl2; (g) 1mol/L NaOH, MeOH; (h) DMP, NaHCO3, CH2Cl2.
Reagents and conditions: (a) Vinylmagnesium bromide, THF; (b) NaBH4, CeCl3, MeOH; (c) TFA, CH2Cl2; (d) HOBT, NMM, EDCI, CH2Cl2; (e) m-CPBA, CH2Cl2, Dess-Martin periodinane, CH2Cl2.
Reagents and conditions: (a) 4 mol/L HCl in dioxane; (b) Boc-α-cyclohexyl-Ala-OH, EDC, HOBt, NMM, DCM; (c) 4mol/L HCl in dioxane; (d) Cbz-Thr(tBu)-OH, EDCI, HOBt, NMM, DCM; (e) LiBH4, THF; (f) Et3N, DMSO, SO3-Pyridine.
Reagents and conditions: (a) m-CPBA; (b) 1mol/L NaOH reflux; (c) Fmoc-His(Trt)-al, BF3.Et2O; (d) Jones reagent; (e) Rink amide resin, DIPCDI, HOBt, DIEA; (f) Piperidine; (g) Cha-Val-Thr-AcOH, TFA-anisole; (h) EtSH, BF3 ·Et2O; (i) NBS.
Reagents and conditions: (a) HNMe2, MeOH; (b) Fluoroacetaldehyde; (c) H2, Pd/C; (d) Cbz-Val-OH, EDCI, HOBT, DMAP; (e) DMP.
Reagents and conditions: (a) CH3CH2CH2C(O)Cl, CH2Cl2, AlCl3; (b) BrCH2COOEt, tBuOK, KI, THF; (c) HCHO, EtOH, K2CO3; (d) DCC, NH2-R1, CH2Cl2.
Reagents and conditions: (a) MeOH, HCl; (b) LiHMDS, THF; (c) 5-(4-chlorophenyl)furan-2-carboxylic acid; (d) 50% aqueous H2SO4.
Reagents and conditions: (a) NaHB(OAc)3, DCE, rt; (b) benzotriazol-1-yl-acetic acid, HATU, TEA, DMF, rt; (c) TFA, DCM; (d) HATU, DIPEA, DMF.
Reagents and conditions: (a) H2, Pd/C, EtOAc; (b) NaNO2, conc. HCl, CuCN, H2O; (c) Boc2O, NiCl2 ·6H2O, NaBH4, MeOH; (d) MeI, KHMDS, THF; (e) LiOH ·H2O, THF/H2O(9:1); (f) (R)-(+)-1-(1-naphthyl)ethylamine 94, EDCI, HOBT, DIPEA, CH2Cl2; (g) TFA, CH2Cl2.
Reagents and conditions: (a) KOtBu, DMSO; (b) 10% HCl, THF; (c) NaHCO3; (d) H2, PtO2, EtOAc; (e) NaCN, DMF; (f) LiOH ·H2O, THF/MeOH/H2O (3 :1 :1); (g) EDCI, HOBT, DIPEA, CH2Cl2/DMF.
Reagents and conditions: (a) TMSCl, PhMgCl, iPrMgCl, LiCl, THF, -20℃; (b) TMSCN, TfOH, TMSOTf, CH2Cl2, -78℃; (c) BCl3, CH2Cl2, -78℃; (d) 2, 2-Dimethoxypropane, H2SO4, acetone, rt; (e) 116, MgCl2, (iPr)2NEt, MeCN, 50℃; (f) 37%HCl, THF, rt; (g) OP(OPh)Cl2, Et3N, CH2Cl2, -78℃; (h) 4-nitrophenol, Et3N, 0℃; (i) iPr2O, 22h, rt, recrystallization.
Reagents and conditions: (a) Et3N, (Boc)2O, water/MeOH; (b) Ac2O, Pyridine; (c) POCl3, PhNMe2, BnNEt3Cl; (d) NaN3, DMF, 80℃; (e) Pd(OH)2/C, H2, MeOH; (f) NaOMe, MeOH; (g) HCl aq..
Reagents and conditions: (a) conc. H2SO4, NaNO2, 0℃, then MeOH, reflux; (b) Pd2(dba)3, BINAP, tBuOK, 80℃; (c) NH3/MeOH; (d) 70% HF-Py, NaNO2, -50~0 ℃; (e) NaI, TMSCl, MeCN, rt; (f) NaHCO3, CH2Cl2, H2O; (g) NH3, EtOH; (h) glyoxal, NaOH/H3PO4, then HCl; (i) Br2, CH3CO2H, Py/DMF; (j) POCl3, TEA; (k) KF/DMF; (l) DCHA, CH3CO2K, CH3CO2H, TEA; (m) NaOH (n) 30% H2O2, HCl.