Facile Synthesis of (2S,3R)-3-Amino-2-hydroxy-4-(4'-hydroxyphenyl)butanoic Acid. Application to the Synthesis of Inhibitors of Aminopeptidases

Facile methods are reported for the synthesis of optically pure derivatives of (2S,3R)-3-amino-2-hydroxy-4-(4'-hydroxyphenyl)b utanoic acid. To avoid troublesome synthesis of O-benzyl-N-Boc-D-tyrosine, without the protection of phenolic OH group of tyrosine N-Boc-D-tyrosine methyl ester was reduced with DiBAL to the aldehyde. The aldehyde was converted via the cyanohydrin to (2S,3R)-3-amino-2-hydroxy-4-(4'-hydroxyphenyl)butanoic acid (AHpHBA). The mixture of diastereomers was converted to the corresponding Boc-AHpHBA methyl ester derivatives and separated by chromatography over silica gel. Optically active (2S,3R)-AHpHBA was used to synthesize aminopeptidase inhibitors.