Theozymes for Intramolecular Ring Cyclization Reactions

A complex of the five-membered transition structure for intramolecular cyclization of 4,5-epoxyhexan-1-ol with the “Houk” theozyme which is 3.5 kcal/mol lower in energy than the complex previously reported as a model for the antibody IgG26D9 catalyzed intramolecular cyclization reverses the preference of that theozyme to favor furan formation. This shows the reported theozyme complex was not a global minima and therefore not a satisfactory model for the antibody reaction. We report a new theozyme favoring pyran formation consistent with the antibody result and the recently published crystal structure of the antibody Fab 5C8 with hapten.