Synthesis of enantiomerically pure 1-amino-2-phenylcycloalkanecarboxylic acids (cnPhe)

Constrained amino acids have become very important tools for modem drug discovery research. Phenylalanine is an appropriate residue for study, due to its participation in active site recognition. The series of 1-amino-2-phenylcycloalkanecarboxylic acids - c(n)Phe - constitutes an attractive family of constrained analogues of phenylalanine that can provide different orientations of the phenyl moiety. All stereoisorners of this series, from the cyclopropane to the cyclohexane members, are available in enantiomerically pure form. 1 Introduction 2 Synthesis of Enantiornerically Pure c(n)Phe Surrogates 2.1 Synthesis of All Stereoisomers of 1-Amino-2-phenylcyclopropanecarboxylic Acid (c(3)Phe) 2.2 Synthesis of All Stereoisomers of 1-Amino-2-phenylcyclobutanecarboxylic Acid (c(4)Phe) 2.3 Synthesis of All Stereoisomers of 1-Amino-2-phenyleyelopentanecarboxylic Acid (c(5)Phe) 2.4 Synthesis of All Stereoisomers of 1-Amino-2-phenylcyclohexanecarboxylic Acid (c(6)Phe) 3 Conclusion