Efficient Method for the Total Asymmetric Synthesis of the Isomers of β-Methyltyrosine

Ernesto Nicolás, K. C. Russell, J. Knollenberg, Victor J. Hruby

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49 Scopus citations

Abstract

α-Amino acids modified at the β-carbon atom can provide topographical constraints when incorporated into a peptide. Such modifications can modulate the physical, chemical, and biological properties of the compound. In order to properly evaluate the effect of such modifications, large-scale asymmetric syntheses of the isomers are needed. A method for the stereoselective large-scale synthesis of all four stereoisomers of β-methyltyrosine is described in this paper. The stereochemistry of both the α- and β-stereocenters was set using 4-phenyl-2-oxazolidinone as a chiral auxiliary. The key reactions were an asymmetric Michael-like addition of an organocuprate to a chiral α,β-unsaturated acyloxazolidinone (β center) and subsequent stereoselective electrophilic bromination of the resulting product (α center). Conversion of the bromide to the azide, catalyzed hydrolysis to the azido acid with simultaneous recovery of the chiral auxiliary, reduction of the azide, and final deprotection of the phenol group afforded the desired amino acids. In general, the reactions were performed in yields over 80%, and the isomers were obtained in enantiomeric purities of 98:2 to 99:1.

Original languageEnglish (US)
Pages (from-to)7565-7571
Number of pages7
JournalJournal of Organic Chemistry
Volume58
Issue number26
DOIs
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Organic Chemistry

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