A simple approach for the synthesis of new pyrimidinyl α-amino acids

Coupling reaction between electron-rich pyrimidinones and α-amino acids promoted by phosphonium salts

“…6 As part of our research was aimed at synthesizing novel, modified antimicrobial peptides by incorporating unnatural a-amino acids, we focused our attention on the synthesis of novel, unnatural pyrimidinyl a-amino acids. Recently, we reported the synthesis of new pyrimidinyl a-amino acids 1 and 2 7 based on methods we established 8 (Scheme 1). In particular, pyrimidin-4-yl a-amino acids 2 were synthesized by a Mitsunobu reaction between 4(3H)-pyrimidinones 3 and N-protected methyl serinate or threoninate.…”

“…However, under Mitsunobu conditions serine and threonine amino acids could lead to the well-documented belimination reaction to obtain the dehydroalanine derivatives 5, 9 and only with N-trityl serine methyl ester the expected compounds 4 could be isolated in high yields (Scheme 1). 7 Besides, the Mitsunobu reaction was limited to a-amino acids with a hydroxyl group in the side chain. Therefore, we sought a method that would allow incorporation of a range of amino acid residues at position 4 of the pyrimidine ring.…”