Reversal of optical induction in transamination by regioisomeric bifunctionalized cyclodextrins

Two isomeric compounds have been synthesized carrying a pyridoxamine on C-6 of beta-cyclodextrin and an imidazole unit on C-6 of the neighboring glucose residue. Each one stereoselectively transaminates phenylpyruvic acid to produce phenylalanine, and with opposite stereochemical preferences. Structure determinations by X-ray crystallography and NMR spectroscopy indicate that the imidazole units serve to block proton addition from their side, rather than acting to protonate the transamination intermediates. Related cyclodextrin-pyridoxamine compounds had been reported carrying ethylenediamine units instead of imidazoles, and high enantioselectivities in transamination were claimed. Our work indicates that these claims are incorrect, and that only poor selectivities are seen that are often unrelated to the position of the ethylenediamine units. Neither of these transaminating systems yet approaches the enantioselectivity seen with a pyridoxamine carrying a chirally mounted internal base group.