Abstract
Cinchona alkaloid catalysts are responsible for the highly enantioselective \r catalysis of over one hundred classes of reaction (1). It is believed that the key to \r understanding this enantioselectivity lies in determining the solution conformation and \r mechanism of the catalyst; however, molecular modeling and NMR studies have \r identified four energy minima, each of which is a candidate for the active conformation, \r and the mechanism is currently uncertain. This study reports the three-dimensional \r structure of Q-7, a quinine derivative responsible for the highly enantioselective \r isomerization of γ-substituted α,β-unsaturated butenolides (2), in complex with tetragonal \r hen egg white lysozyme at 1.8 Å resolution. This atomic-resolution structure of the \r catalyst is suggestive as to the active conformation of Q-7 and represents a new system \r that may allow visualization of the catalyst-reactant complex for this and many other \r organic catalysts of unknown structure and mechanism. Progress has also been made \r toward obtaining a ternary structure with both Q-7 and its substrate, and preliminary data \r suggest that Q-7’s catalytic activity is not abolished by coordination to lysozyme.