Selective, on-resin N-methylation of peptide N-trifluoroacetamides.
Mild and efficient methods for site-specific methylation of peptide backbone amides are important tools for chemists seeking to modulate the pharmacokinetic properties of peptide drugs. The Mitsunobu reaction was used to selectively methylate N-trifluoroacetamide (Tfa) protected peptides on-resin. The Tfa group was removed quickly and completely by reduction with excess NaBH4, and it was shown to be orthogonal to many of the protecting groups used in solid-phase peptide synthesis.
Department of Chemistry and Biochemistry, University of California at Santa Cruz , 1156 High Street, Santa Cruz, California 95064, United States.
Rushia A
RA
Turner
Niels E
NE
Hauksson
Jordan H
JH
Gipe
R Scott
RS
Lokey
D000081:Acetamides / Q000737:chemistry*; D000577:Amides / Q000737:chemistry*; D005463:Fluoroacetates / Q000737:chemistry*; D008745:Methylation; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D060327:Solid-Phase Synthesis Techniques
D000081:Acetamides; D000577:Amides; D005463:Fluoroacetates; D010455:Peptides; C030688:trifluoroacetamide