New C‐protective group for peptide synthesis: Application of 2‐(1‐adamantyl)‐propanol‐2 esters

To investigate the possibility of using the 2‐(1‐adamantyl)‐2‐propyl (Adp) ester group for carboxyl protection during peptide synthesis, the tetrapeptide Boc‐Phe‐Arg(NO ₂ )‐Phe‐Pro‐OAdp (IV) was prepared by the carbodiimide method. In this synthesis the Z group was removed by transfer hydrogenation and the Nps group by treatment with 2‐thiopyridone. The Adp group was then cleaved with 3 % TFA/DCM, yielding Boc‐Phe‐Arg(NO ₂ )‐Phe‐Pro‐OH. For subsequent kinetics studies the decapeptide Boc‐Leu— Z‐Orn‐Arg(NO ₂ )‐Pro‐Pro‐Gly‐Phe‐Ser(Bzl)‐Pro‐Pro‐OAdp (VIII) was synthesized by a 9 + 1 scheme. This peptide was also selectively deblocked. Comparing reaction abilities of Z‐Pro‐OAdp and Z‐Pro‐OBu ^t , it was demonstrated that the Adp ester is cleaved by 3% TFA/DCM 230 times faster than the Bu ^t ester. For peptides IV and VIII the ratios between the rates of competitive elimination of the Adp and Boc groups by 3% TFA/DCM are 19 and 64, respectively.