W. Kazmierski, Z. Urbańczyk-Lipkowska, V. Hruby
Apr 1, 1994
Citations
0
Influential Citations
39
Citations
Journal
Journal of Organic Chemistry
Abstract
The synthesis of all four diastereoisomers of α,β-dimethylphenylalanine (4) as well as those of α,β-dimethyl-1,2,3,4,-tetrahydroisoquinoline-3-carboxylic acid (5 and 6) have been accomplished in high yield and high optical purity. Molecular mechanics calculations on the N α -acetyl and N-methylcarboxamide derivatives of (3R,4R)-6 and (3R,4S)-5 indicate large and moderate stabilization for the gauche(-) but not the gauche(+) side-chain conformers of (3R,4S)-5 and (3R,4R)-6, respectively. By symmetry rules, the same holds for (3S,4R)-5 and (3S,4S)-6, respectively. Thus, these amino acids are potential building blocks for the topographical design of peptides by providing acylated 1,2,3,4-tetrahydroisoquinoline-3-carboxylic derivatives in which a gauche (-) and not a gauche (+) side-chain conformation is energetically more stable for the L amino acid. Synthetic details and implications of these new amino acids for peptide and protein design are discussed