Selective acidolytic cleavage of the tert-butoxycarbonyl group

Abstract

In the presence of the PhCH2O2C group (Z), the tert-BuO2C group (Boc) cannot be cleaved selectively by CF3CO2H or by CF3CO2H-HCl in org. solvents. Substituted Z groups, such as p- or m-ClC6H4CH2O2C or p-O2NC6H4CH2O2C, are more stable, but are also either slowly split off by the above reagents or are stable towards acidolysis. Selective removal of Boc groups can be achieved with 70% aq. CF3CO2H. There occurs simultaneous hydrolysis of benzyl esters, esp. in glutamic acid. This procedure was used in the stepwise synthesis of the insulin sequence B 24-30. BF3-etherate-HOAc is also effective in selective cleavage of Boc groups; benzyl esters are more stable towards BF3 than towards aq. CF3CO2H. BF3 is esp. advantageous for the removal of Boc in peptide derivs. with acid-labile HS-protecting groups, such as tetrahydropyranyl or trityl, and in the presence of cyclocystinyl. This method was used in the synthesis of the 2 peptide derivs. [with protection of SH by the trityl (Trt) group] Boc-Leu-Cys(Trt)-Gly and Boc-Leu-Val-Cys-(Trt)-Gly. During prolonged action, acetylation of aliphatic OH groups may occur, but this reaction can be avoided by using other solvents. [on SciFinder (R)]