Asymmetric synthesis of unusual amino acids

An efficient synthesis of optically pure isomers of β-methylphenylalanine.

Ramalinga Dharanipragada, Katia VanHulle, Anne Bannister, Soaring Bear, Lisa Kennedy, Victor J Hruby

Research output: Contribution to journalArticle

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Abstract

Substitution of the diastereotopic β-hydrogens of many α-amino acids provides an approach to the three dimensional topographic control of peptide structure. Asymmetric synthesis of the desired amino acids is needed to facilitate these studies. All four individual isomers of β-methylphenylalanine, (2S,3S)-, (2R,3R)-, (2S,3R)- and (2R,3S)-β-methylphenylalanine have been synthesized in high optical purity. The stereochemistry at the β-center was set by the choice of starting material, either (+)- or (-)-3-phenylbutyric acid. These acids were attached to the appropriate D- or L-auxiliary (a 4-phenylmethyl-2-oxazolidinone) to give a 3′-phenylbutanoyl-4-phenylmethyl-2-oxazolidinone. Asymmetric bromination was accomplished via the ciral imide enolate bromination methodology of Evans and co-workers (J. Am. Chem. Soc. 1990 112, 4011-40). Evidence for asymmetric induction was obtained from the X-ray structure of one of the intermediate bromides. The bromide was converted to the diastereoisomeric azide by SN2 displacement using tetramethylguanidinium azide. After recovery of the chiral auxiliary by catalyzed hydrolysis, the chiral amino acid was obtained by catalytic hydrogenation over 10% Pd/C. All four isomers were obtained in enantiomeric purities of 95:5 to 99:1.

Original languageEnglish (US)
Pages (from-to)4733-4748
Number of pages16
JournalTetrahedron
Volume48
Issue number23
DOIs
StatePublished - Jun 5 1992

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Isomers
Oxazolidinones
Azides
Halogenation
Bromides
Amino Acids
Imides
Stereochemistry
Hydrogenation
Hydrogen
Hydrolysis
Substitution reactions
X-Rays
Recovery
X rays
Peptides
Acids
3-phenylbutyric acid

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Asymmetric synthesis of unusual amino acids : An efficient synthesis of optically pure isomers of β-methylphenylalanine. / Dharanipragada, Ramalinga; VanHulle, Katia; Bannister, Anne; Bear, Soaring; Kennedy, Lisa; Hruby, Victor J.

In: Tetrahedron, Vol. 48, No. 23, 05.06.1992, p. 4733-4748.

Research output: Contribution to journalArticle

Dharanipragada, Ramalinga ; VanHulle, Katia ; Bannister, Anne ; Bear, Soaring ; Kennedy, Lisa ; Hruby, Victor J. / Asymmetric synthesis of unusual amino acids : An efficient synthesis of optically pure isomers of β-methylphenylalanine. In: Tetrahedron. 1992 ; Vol. 48, No. 23. pp. 4733-4748.
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