INHERENT CONFORMATION OF THE BIOTIN BICYCLIC MOIETY - SEARCHING FOR AROLE FOR SULFUR

The inherent conformation of the biotin bicyclic moiety has been exami ned. In biotin and various heterobiotins the endo conformation of the bicyclic ring is always observed; however, the presence of a side chai n in the native coenzyme and its analogs may preclude the alternative exo conformation, masking what may be an inherently more favored confo rmation. The crystal structures of the three chainless analogs of biot in, oxybiotin, and azabiotin have been determined, and in all cases th e bicyclic rings adopt the endo conformation, with the heteroatom prox imal to the ureido ring. In contrast, ah initio quantum calculations a nd high-resolution nuclear magnetic resonance experiments on the chain less analog of biotin suggest that the endo and exo conformations of t he bicyclic ring are of comparable energy and coexist in approximately equal amounts in solution.