New Amino Acids for the Topographical Control of Peptide Conformation: Synthesis of All the Isomers of α,β-Dimethylphenylalanine and αβ-Dimethyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic Acid of High Optical Purity

Wieslaw M. Kazmierski, Zofia Urbanczyk-Lipkowska, Victor J. Hruby

Research output: Contribution to journalArticle

60 Scopus citations

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 Nα-acetyl and N-methylcarboxamide derivatives of (3R,4R)-6 and (3R,4S)-5 indicate large and moderate energy 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 (Kazmierski et al., J. Am. Chem. Soc. 1991,113,2275-2283) by providing acylated 1,2,3,4-tetrahydroisoquinoline- 3-carboxylic acid 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.

Original languageEnglish (US)
Pages (from-to)1789-1795
Number of pages7
JournalJournal of Organic Chemistry
Volume59
Issue number7
DOIs
StatePublished - Apr 1 1994

ASJC Scopus subject areas

  • Organic Chemistry

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