Efficient method for the total asymmetric synthesis of the isomers of .beta.-methyltyrosine

• Published in: Journal of organic chemistry Vol. 58; no. 26; pp. 7565 - 7571
• Main Authors: Nicolas, Ernesto, Russell, K. C, Knollenberg, J, Hruby, Victor J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.12.1993; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Exact sciences and technology; Noncondensed benzenic compounds; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; ALPHA; DESIGN; OPTICALLY PURE ISOMERS; ANALOGS; UNUSUAL AMINO-ACIDS; METHYLPHENYLALANINE; Michael addition; α-Aminoacid; Chiral auxiliary; Asymmetric synthesis; Phenols; Benzenic compound; Methylation; Organic carbamate
• DOI: 10.1021/jo00078a042
• ISSN: 0022-3263

Alpha-Amino acids modified at the beta-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 an four stereoisomers of beta-methyltyrosine is described in this paper. The stereochemistry of both the alpha- and beta-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 alpha,beta-unsaturated acyloxazolidinone (beta center) and subsequent stereoselective electrophilic bromination of the resulting product (alpha 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.