Resolution of synthetically useful myo-inositol derivatives using the chiral auxiliary O-acetylmandelic acid

Abstract

Efficient methods for the resolution of various myo-inositol derivatives have been developed using O-acetylmandelic acid (OAM) as the chiral auxiliary. Various methods of introduction of the chiral auxiliary have been compared. DCC mediated coupling between the inositol derivative and O-acetylmandelic acid resulted in substantial racemization even at 0 °C; while acylation with O-acetylmandeloyl chloride in the presence of pyridine gave the diastereomers without any racemization of the chiral auxiliary. The advantage of using OAM as a chiral auxiliary is that the absolute configuration of the resolved diastereomers can be determined by analyzing the 1H NMR chemical shifts of various protons. The diastereomeric separation has been achieved either by fractional crystallization or column chromatography. The enantiomers of inositol derivatives could be obtained by the removal of chiral auxiliaries. By employing the known selective protection–deprotection strategies, various derivatives in optically active form could be synthesized.