Synthesis of the four stereoisomers of 1-azabicyclo[2.2.2]oct-3-yl-α-hydroxy-α-(4-phenylboronic acid)-α-phenylacetate (QNB-boronic acid), including a preparative HPLC method to separate diastereoisomeric mixtures with high optical purity

The four stereoisomers of 1-azabicyclo[2.2.2]oct-3-yl-α-hydroxy-α-(4-phenylboronic acid)-α-phenylacetale (QNB boronic acids, 1a-1d ) were synthesized initially via 1-azabicyclo[2.2.2]oct-3-yl-α-hydroxy-α-(4-iodophenyl)-α-phenylacetate (iodo-QNBs, 6a-6d) using an adaptation of a published procedure. The number of steps involved were reduced substantially using a distinctly different approach. This involved the synthesis of diastereoisomers of QNB-boronic acid, followed by separation and isolation of enantiomers by preparative reversed-phase HPLC. An improved method of synthesis of α-hydroxy-α-(4-aminophenyl)-α-phenyl-acetic acid ( 3a and 3b ) from α-hydroxy-α-(4-nitrophenyl)-α-phenylacetic acid ( 2a and 2b ) is also described.