STRUCTURE AND CONFORMATION OF MANNOAMIDINES BY NMR AND MOLECULAR MODELING - ARE THEY GOOD TRANSITION-STATE MIMICS

The conformation of two mannose-based amidines, the N-benzylmannoamidi ne and a pseudo (1-->6) dimannoside, has been evaluated using semi-emp irical AM1 calculations and H-1 NMR studies. The most stable conformat ions of the mannoamidine ring correspond to the half-chair forms H-3(4 ) and H-4(3). The conformations (Z) or (E) about the exocyclic C-N bon d depend on the substituents and it was shown that, in solution, the N -benzylmannoamidine was (E)-configured whilst the pseudo (1-->6) diman noside was (Z)-configured. Using the grid-search approach, the potenti al energy maps of both mannoamidines were calculated as a function of the torsion angles which define the orientation of the amidine substit uent. Three stable conformers were identified for the N-benzylmannoami dine and seven for the pseudo (1-->6) dimannoside. Inter-glycosidic NO E have provided evidence for a preferred conformation of the pseudo (1 -->6) dimannoside in solution. The transition state structure of the a lpha-phenylmannose hydrolysis was optimized using the AM1 method and c ompared to the N-benzylmannoamidine. The developing oxocarbenium ion i s well matched by the mannoamidine ring but the orientation of the phe nyl group in the inhibitor differs significantly from the position of the leaving group in the transition state. The use of sugar type amidi nes as haptens to obtain catalytic antibodies is then discussed.