Facile synthesis of alpha,alpha-diisobutylglycine and anchoring its derivatives onto PAL-PEG-PS resin.

alpha,alpha-Diisobutylglycine has been synthesized using a Pd-mediated dialkylation of ethyl nitroacetate as a key first step. The free alphaalphaAA is N(alpha)-protected and has been applied to the assembly of conformationally constrained peptide analogues. Mixed anhydrides from BOP-Cl and Fmoc-alphaalphaAA-OH are used for anchoring alphaalphaAAs onto a trialkoxybenzyl linker on PEG-PS grafted support, upon which a beta-strand mimic with difficult sequence is assembled in a superior quality.