Abstract
Azido acids are important synthons for the synthesis of complex peptides. As a protecting
group, the azide moiety is atom-efficient, easy to install and can be reduced in the
presence of many other protecting groups, making it ideal for the synthesis of branched
and/or cyclic peptides. α-Azido acids are less bulky than urethane-protected counterparts
and react more effectively in coupling reactions of difficult-to-form peptide and
ester bonds. Azido acids can also be used to form azoles on complex intermediates.
This review covers the synthesis of azido acids and their application to the total
synthesis of complex peptide natural products.
1 Introduction
2 Synthesis of α-Azido Acids
2.1 From α-Amino Acids or Esters
2.2 Via α-Substitution
2.3 Via Electrophilic Azidation
2.4 Via Condensation of N-2-Azidoacetyl-4-Phenylthiazolidin- 2-Thi one Enolates with Aldehydes and Acetals
2.5 Synthesis of α,β-Unsaturated α-Azido Acids and Esters
3 Synthesis of β-Azido Acids
3.1 Preparation of Azidoalanine and 3-Azido-2-aminobutanoic Acids
3.2 General Approaches to Preparing β-Azido Acids Other Than Azi doalanine and
AABA
4 Azido Acids in Total Synthesis
4.1 α-Azido Acids
4.2 β-Azido Acids and Azido Acids Containing an Azide on the Side
Chain
5 Conclusions
Key words
peptides - azido acids - azides - total synthesis - azidation - diazo transfer
