DESIGN OF CHOLIC-ACID HOSTS FOR MOLECULAR RECOGNITION OF MONOSACCHARIDES USING SYSTEMATIC CONFORMATIONAL SEARCHING

A rigorous molecular mechanics conformational analysis strategy, which utilizes a combination of scanning by energy and by distance, has bee n employed to identify all of the potential three-dimensional shapes w hich four cholic acid hosts (CAHs) can adopt in low energy conformatio ns. Each CAH showed a unique profile of shapes (''C'', ''cup'', ''L'' and ''S'') and preference for guests, based upon cavity size and hydro gen-bonding potential. Focusing on the population of ''C'' or clam sha pes with about 8-12 angstrom binding cavity resulted in a clear choice for a synthetic target as a molecular receptor for glucose: cmCAH (3) > pCAH (2) > mCAH (1) > cpCAH (4). The strategy was verified by desig ning two ''locked-in'' macrocyclic host structures for 3, each of whic h demonstrated good steric and hydrogen-bonding complementarity with a guest.