Recent Advances in the Synthesis of Fluorinated Amino Acids

Abstract

Introduction of fluorine atoms or fluorine‐containing groups into amino acids has attracted much attention from bioorganic and medicinal chemists because the resulting fluorinated amino acids have found wide application as potential enzyme inhibitors and antitumor (antibacterial) agents. Additionally, it is well known that replacement of naturally occurring amino acid(s) in some peptide chains with their fluorinated counterparts can significantly increase specific protein–ligand or protein–protein interactions, leading to increases in the proteolytic and thermal stabilities of peptide compounds and, as a result, promote their therapeutic properties. This microreview summarizes important advances in the synthesis of fluorinated amino acids since 2005. The contents are simply divided into three groups on the basis of amino acid types: fluorinated α‐amino acids (F‐αAAs), fluorinated β‐amino acids (F‐βAAs), and fluorinated cyclic amino acids (F‐CAAs).

Efficient regio- and stereoselective access to novel fluorinated β-aminocyclohexanecarboxylates

“…These changes in properties may be more appreciable in the case of peptide oligomers formed from conformationally restricted fluorinated amino acids. Although cyclic β-amino acids are of major interest in pharmaceutical chemistry and in peptide research [36–60], only a relatively small number of fluorinated derivatives of this class of compounds have been synthesized so far [61–70]. …”

A direct route for the preparation of Fmoc/O Bu protected iodotyrosine

“…The halide functionality has also been used to introduce fluorine tags into biomolecules 7,8 and as key components in natural product synthesis. 9,10 Iodotyrosines have been widely utilised in natural product synthesis [11][12][13] and the formation of unnatural bi-aryl amino acids.…”

Biosynthetic Incorporation of Fluorinated Amino Acids into Peptides and Proteins

“…[3] Naturally occurring fluorinated peptides and proteins are unknown. Even so, numerous methods have been developed for the synthesis of a wide range of fluorinated amino acids, [4,5] and the incorporation of many of these has been investigated (Figs 2-4). Those substituted with fluorine at either the aor b-position are relatively difficult to prepare due to their propensity to undergo dehydrofluorination and, even though methods have been developed for chemical synthesis of corresponding peptides, [6,7] these amino acids are unsuitable for biochemical approaches.…”