Conformational analysis of natural products using long-range carbon-proton coupling constants: Three-dimensional structure of okadaic acid in solution

Long-range carbon-proton coupling constants (^2,3J_C,H) are known to depend on the dihedral angles as is the well-known case with interproton couplings. The precise measurement of these J values were carried out using hetero half-filtered TOCSY and phase-sensitive HMBC on a marine natural product, okadaic acid. From the obtained values together with ³J_H,H we disclosed the conformations of okadaic acid in organic and aqueous solutions (CD₃OD-CDCl₃ or NaOD/D₂O), which resembled each other and that obtained for its crystalline o-bromobenzyl ester. The successful result in the present conformational study, even though as an exmaple, demonstrated this methodology to be powerful in elucidation of conformations and configurations of acyclic or macrocyclic portions in natural products of this size.