Synthesis of dipeptides from N-hydroxy-3-azaspiro[5,5]undecane-2,4-dione activated α-amino acids

A simple two step procedure for the synthesis of a dipeptide from N-hydroxy-3-azaspiro[5,5]undecane-2,4-dione (HO-ASUD) activated α-amino acids is described. In presence of DCC, N-hydroxy-3-azaspiro[5,5]undecane-2,4-dione readily esterifies the carboxylic acid group of all the N-protected amino acids to yield crystalline N-hydroxy-3-aza spiro[5,5]undecane-2,4-dione activated carboxy ester. The N-hydroxy-3-aza spiro[5,5]undecane-2,4-dione activated carboxy esters of N-protected amino acids readily condensed with other amino acids and gave a dipeptide. This new method is effective for the DCC coupling of a variety of chiral amino acids without loss of enantiomeric purity. Synthesis of fifteen dipeptides including the hitherto unreported Fmoc-l-Orn(Boc)-Val-OMe, Fmoc-l-Cys(trt)-Gly-OEt and Boc-l-Tyr-Gly-OEt is presented.