Sm. Evans et al., DESIGN OF CHOLIC-ACID HOSTS FOR MOLECULAR RECOGNITION OF MONOSACCHARIDES USING SYSTEMATIC CONFORMATIONAL SEARCHING, Journal of molecular structure. Theochem, 114, 1994, pp. 159-174
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.