Synthesis of histidinoalanine: A comparison of β-lactone and sulfamidate electrophiles

摘要

Previous syntheses of histidinoalanine (HAL) have led to mixtures of regioisomers and/or stereoisomers. For example, opening of N-Cbz-d-serine- β-lactone (6) with Boc-l-His-OMe (5) gave a 2:1 mixture of τ- and π-regioisomers. The sulfamidate 10, derived from N-benzyl-d-serine methyl ester (11), was reacted with Boc-l-His-OMe (5) to give the τ-HAL derivative 17 as a sing e isomer in 57% yield. A similarly prepared τ-HAL 19, bearing protecting groups that were all hydrogenolytically labile, led to the free bis-amino acid, τ-l-histidinyl-d-alanine (τ-4), as a salt-free standard for amino acid analysis.