Individual stereoisomers of phosphinic dipeptide inhibitor of leucine aminopeptidase

Abstract

Individual stereoisomers of the phosphinic pseudodipeptide hPhepsi[P(O)(OH)CH(2)]Phe were obtained by stereoselective liquid chromatographic separation as N- and C-terminally protected derivative on quinidine carbamate modified silica stationary phase. The stereoisomeric purity, exceeding 95% for each fraction, was determined before and after deprotection using two independent methods. The absolute configuration was rationally assigned by application of enantiomerically pure phosphinic acid substrates in the synthetic procedure and correlation with biological activity of the products. Substantial differences in inhibition of leucine aminopeptidase by the individual isomers revealed novel insights into potency of the recently developed and remarkably effective compound.