Synthesis of the Four Stereoisomers of 1-Azabicyclooct-3-yl-α-hydroxy-α-(4-phenylboronic acid)-α-phenylacetae (QNB-Boronic acid), including a preparative HPLC method to separate diastereoisomeric mixtures with high optical purity

Article abstract of DOI:10.1016/S0957-4166(00)82085-6

The four stereoisomers of 1-azabicyclo<2.2.2>oct-3-yl-α-hydroxy-α-(4-phenylboronic acid)-α-phenylacetate (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 reducted 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.