The carbenoid approach to peptide synthesis.
A different approach to the synthesis of dipeptides is described based on the formation of the NHCHR1CONH-CHR2CO bond by carbenoid N-H insertion, rather than the formation of the peptide bond itself. Thus decomposition of triethyl diazophosphonoacetate catalysed by rhodium(II) acetate in the presence of N-protected amino acid amides 8 gives the phosphonates 9. Subsequent Wadsworth-Emmons reaction of 9 with aldehydes in the presence of DBU gives dehydro dipeptides 10. The reaction has been extended to a simple two-step procedure, without the isolation of the intermediate phosphonate, for conversion of a range of amino acid amides 11 into dehydro dipeptides 12 and to an N-methylamide 11 h, and for conversion of a dipeptide to tripeptide (13-->14). Direct conversion, by using methyl diazophenylacetate, of amino acid amides to phenylglycine-containing dipeptides 19 proceeds in good chemical yield, but with poor diastereoselectivity.
Buck
R T
RT
School of Chemistry, University of Exeter, Devon, UK.
Clarke
P A
PA
Coe
D M
DM
Drysdale
M J
MJ
Ferris
L
L
Haigh
D
D
Moody
C J
CJ
Pearson
N D
ND
Swann
E
E
D000577:Amides / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D010452:Peptide Biosynthesis; D013055:Spectrophotometry, Infrared
D000577:Amides; D000596:Amino Acids