Synthesis of new unnatural N^α-Fmoc pyrimidin-4-one amino acids: use of the p-benzyloxybenzyloxy group as a pyrimidinone masking group

Abstract

The p-benzyloxybenzyloxy group is used to mask the oxo function of the 4(3H)-pyrimidinone ring in the synthesis of new unnatural amino acids. The synthetic approach is based on an aromatic nucleophilic substitution reaction between 4-[4-(benzyloxy)benzyloxy]-2-(benzylsulfonyl)pyrimidine and the nucleophilic side chain of several N(α)-Boc amino esters, as the key step, followed by a series of standard protecting group transformations. p-Benzyloxybenzyloxy is efficiently removed under mild acid conditions to recover the 4(3H)-pyrimidinone system.

Enantioselective Synthesis of D‐α‐(Uracil‐5‐yl)glycine Derivatives and Their Racemization‐Free Incorporation into a Model ­Peptide

“…This is an important field in bioorganic chemistry, as the genetic incorporation of such structures allows detailed studies of the structure and function of proteins. [1][2][3][4][5][6][7][8] Nucleobase amino acids (NBAs) are of particular interest, since they can be found in a variety of natural products. Examples include the secondary metabolites (S)-willardiine and (S)-isowillardiine, which show interesting pharmacological properties and can act as potent antagonists of AMPA receptors (AMPA = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) or GluR5-containing kainate receptors (Figure 1, a).…”