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The Carbenoid Approach to Peptide Synthesis
Author(s) -
Buck Richard T.,
Clarke Paul A.,
Coe Diane M.,
Drysdale Martin J.,
Ferris Leigh,
Haigh David,
Moody Christopher J.,
Pearson Neil D.,
Swann Elizabeth
Publication year - 2000
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20000616)6:12<2160::aid-chem2160>3.0.co;2-y
Subject(s) - carbenoid , chemistry , tripeptide , dipeptide , peptide bond , phosphonate , amino acid , yield (engineering) , stereochemistry , peptide , peptide synthesis , combinatorial chemistry , rhodium , organic chemistry , catalysis , biochemistry , materials science , metallurgy
A different approach to the synthesis of dipeptides is described based on the formation of the NHCHR 1 CONH−CHR 2 CO 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.