Preparation of protected syn-alpha,beta-dialkyl beta-amino acids that contain polar side chain functionality.
We report the synthesis of syn-alpha,beta-dialkyl beta-amino acid derivatives suitably protected for solid-phase synthesis that give rise to residues containing positively charged lysine-like side chains. These amino acids, as well as syn-alpha,beta-dialkyl beta-amino acids that contain diverse hydrophobic side chains, are prepared in good de and ee. The key step in this route involves Davies's protocol for the conjugate addition of a chiral lithium amide to alpha,beta-unsaturated tert-butyl esters (Davies, S. G.; Ichihara, O.; Walters, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 9, 1141). syn-alpha,beta-Dialkyl beta-amino acids are interesting building blocks because of their sheet-forming propensity and because of their presence in bioactive compounds.
Langenhan
Joseph M
JM
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706-1396, USA.
Gellman
Samuel H
SH
D000596:Amino Acids / Q000138:chemical synthesis*; D002855:Chromatography, Thin Layer; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D013237:Stereoisomerism
D000596:Amino Acids; D007202:Indicators and Reagents