(2R)- and (2S)-3-fluoroalanine and their N-methyl derivatives: synthesis and incorporation in peptide scaffolds.
A convergent synthetic methodology has been developed to access both (2S)- and (2R)-3-fluoroalanine and their corresponding N-methyl analogues, in optically pure form, through a common oxazolidinone intermediate that can be obtained from L- or D-serine. In addition, a procedure for incorporation of these unnatural amino acids in peptide scaffolds is also disclosed herein that minimizes the occurrence of beta-elimination during amide bond formation. [reaction: see text]
Hoveyda
Hamid R
HR
Tranzyme Pharma Inc., Institut de pharmacologie de Sherbrooke, 3001 12th Avenue Nord, Sherbrooke, Québec J1H 5N4, Canada. hhoveyda@tranzyme.com
Pinault
Jean-François
JF
D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000577:Amides / Q000737:chemistry; D000596:Amino Acids; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D008745:Methylation; D023303:Oxazolidinones / Q000138:chemical synthesis / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D012694:Serine / Q000737:chemistry
D000577:Amides; D000596:Amino Acids; D007202:Indicators and Reagents; D023303:Oxazolidinones; D010455:Peptides; C007742:3-fluoroalanine; D012694:Serine; D000409:Alanine