Preparation of Some 2‐phenylisopropyloxycarbonyl Amino Acids. Evaluation of Their Properties With Particular Reference to Application in Solid Phase Peptide Synthesis

For temporary protection of the α‐amino function in amino acids to be used in peptide synthesis in general and solid‐phase peptide synthesis in particular, some new 2‐phenylisopropyloxycarbonyl amino acids have been prepared from the corresponding phenyl carbonate in dimethylsulphoxide using tetramethylguanidine as the base. Experiments so far indicate that these derivatives might be attractive as a substitute for the structurally related, very acid‐labile Bpoc‐amino acids, whose main advantages they seem to share. In our opinion, however, 2‐phenylisopropyloxycarbonyl amino acids have several advantages over Bpoc‐derivatives. They are much more economically prepared, generally more easily characterized, and show improved stability on storage. Their preparation on any laboratory scale is nearly as simple as in the case of Boc‐ and Z‐amino acids. Rate profiles for removal of the protecting group under solid‐phase peptide synthesis conditions are presented. Finally, the new derivatives have been applied to the synthesis of bradykinin using Merrifield's technique.