One-pot preparation of N-(carbonylamino)amino acids and half-acid/half-ester urea dipeptides directly from α-amino acids

N-(Carbonylamino)amino acids and half-acid/half ester urea dipeptides can be prepared in a "one-pot" sequence directly from alpha-amino acids by employing TMS as a "transient" protecting group. The 4-step sequence: selective O-silylation of the alpha-amino acid, transformation of the amino group to the isocyanate, reaction of the isocyanate with an amine or amino acid ester, and mild deprotection using MeOH affords the N-(carbonylamino)amino acids or half-acid/half ester urea dipeptides in overall yields ranging from 45-85%. Comparison of chiral HPLC assays of an enantiomeric pair of products prepared from their respective L- and D-amino acids using this methodology indicates that no racemization occurs during the sequence. (C) 1999 Elsevier Science Ltd. All rights reserved.