sodium carbonate in water 4 h; Ambient temperature;

1: BOC-glycine; C14H14NPol With benzotriazol-1-ol; diisopropyl-carbodiimide in N,N-dimethyl-formamide solid phase reaction; 2: With trifluoroacetic acid in dichloromethane 0.5 h; solid phase reaction; 3: BOC-glycine; 1-(tert-butoxycarbonyl)-L-proline; N-tert-butoxycarbonyl-L-leucine; boc-Ng-tosyl-L-arginine; N-tert-butoxycarbonyl-O-benzyl-L-serine; Boc-L-tyrosine(2-Br-Z)-OH; boc-Trp(CHO)-OH; Boc-pGlu-OH; N-Boc-L-His(Tos)-OH Further stages;

1: C21H31N2O5Pol With trifluoroacetic acid in dichloromethane 0.5 h; solid phase reaction; 2: N-Boc-L-His(Tos)-OH With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine in 1-methyl-pyrrolidin-2-one; dimethyl sulfoxide 3 h; solid phase reaction; 3: 1-(tert-butoxycarbonyl)-L-proline; t-Boc-L-valine; (2S,3S)-2-(tert-butoxycarbonylamino)-3-methylpentanoic acid; N-tert-butoxycarbonyl-L-phenylalanine; boc-Ng-tosyl-L-arginine; (2S)-3-cyclohexyloxycarbonyl-2-t-butoxycarbonylaminopropanoic acid; Boc-L-tyrosine(2-Br-Z)-OH; N-Boc-L-His(Tos)-OH Further stages;

1: C24H29N2O5Pol With trifluoroacetic acid in dichloromethane 0.5 h; solid phase reaction; 2: 1-(tert-butoxycarbonyl)-L-proline With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine in 1-methyl-pyrrolidin-2-one; dimethyl sulfoxide 3 h; solid phase reaction; 3: t-Boc-L-valine; (2S,3S)-2-(tert-butoxycarbonylamino)-3-methylpentanoic acid; boc-Ng-tosyl-L-arginine; (2S)-3-cyclohexyloxycarbonyl-2-t-butoxycarbonylaminopropanoic acid; Boc-L-tyrosine(2-Br-Z)-OH; N-Boc-L-His(Tos)-OH Further stages;

trimethylsilyl trifluoromethanesulfonate; 4,4'-diphenylsulfide in trifluoroacetic acid T=0°C; 0.5 h; New peptide deprotection procedure: hard-soft acid-base concept; the role of soft bases (thioanisole, dimethylsulfide, diphenylsulfide) employed.; Product distribution;

Multistep reaction;

1: 72 percent / NaH / tetrahydrofuran / 16 h / Ambient temperature 2: Et3N, diethylphosphoryl cyanide / CH2Cl2 / Ambient temperature 3: 5.81 g / CF3COOH / CH2Cl2 / Ambient temperature 4: 78 percent / Et3N, diethylphosphoryl cyanide / CH2Cl2 / Ambient temperature 5: 5.4 g / CF3COOH / CH2Cl2 / Ambient temperature 6: 97 percent / Et3N, diethoxyphosphoryl cyanide / CH2Cl2 / Ambient temperature 7: 85 percent / 1-hydroxybenzotriazole / methanol / 24 h / Ambient temperature View Scheme