Solution and Solid Phase Synthesis of Unusual a-Amino Acids From

2.1 Introduction
Chapter Two
Synthesis of Boc Protected &Hydroxy-a-Amino Acids
p-Hydroxy-a-amino acids are of immense interest due to either their direct
biological action or as structural components of compounds with biological activities
(Figure 2.1).'.' For example, D-do-threonine is found in antibiotics such as the
katanosins 2.1,3 while &hydroxyleucine is found in the leucinostatins 2.2 and the
katanosins 2.1. B-Hydroxytyrosine is present in antibiotics such as vancomycin 2.3'
(widely used to treat deep seated Gram negative bacterial infections), the orienticins 2A6
and chloroorienticins 2.5,' risocetins 2.@ and chloramphenicol2.~ and a number of other
cyclic peptides (avoparcin, teicoplanin, actapanin, parvocidin, actinodin, and
chloropolysp~rin).~ The catecholamine class of neurotransrnitters (adrenaline 2.8 and
norepinephrine 2.9) incorporate a ~hydroxytyrosine moiety whereas epinephrine 2.10
contains P-hydroxyphenylalanine. p-Hydroxyproline and fbhydroxyaspartic acid have
been isolated from empedopeptin1° and p-hydroxyaspartic acid is also believed to play a
role in hemeostasis proteins." 8-Hydroxyglutamine has been identified in antibiotics
such as neopep tin.12 (4R)-4-(E)-2-Butenyl-4J-dimethyl-L-threonine 2.1 1, probabl y the
most well known f3-hydroxy-a-amino acid, is a crucial constituent of cyclosporin A, a
potent irnmunosuppressive drug." b-Hydroxy-a-arnino acids are also important
intermediates in the synthesis of other compounds, for exarnple, many p-Iactams (with
antimicrobial activity) have been synthesized via B-hydroxy-a-arnino acids.I4